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Cited by 452Gut microbiota and healthNutritional Studies and DietGastrointestinal motility and disorders

Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health

Open access
Berding, Kirsten, Vlckova, Klara, Marx, Wolfgang, Schellekens, Harriet, Stanton, Catherine, Clarke, Gerard, Jacka, Felice, Dinan, Timothy G +1 more·2021·Advances in Nutrition
DOI 10.1093/advances/nmaa181PMC PMC8321864
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Abstract

Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.

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  • Findingcitation

    In rats, a high-fat diet increased depressive-like behavior (immobility time and swimming behavior).

    “↑ Depressive-like behavior | (immobility time and | swimming behavior) after | HFD”
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  • Findingcitation

    In rats, a diet supplemented with galactooligosaccharide, polydextrose, lactoferrin, whey protein concentrate and milk-fat globule membrane decreased anxiety-like behavior.

    “↓ Anxiety-like behavior”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Findingcitation

    In mice, germ-free status and antibiotic treatment abolish the antiseizure effect of a ketogenic diet.

    “Germ-free status and antibiotic | treatment abolish antiseizure | effect of KD”
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  • Findingcitation

    In rats, diets enriched in sugar, SFAs or PUFAs differentially affected the gut microbiota at class, order, family, genus and OTU levels, with 89 taxa contributing to differences among diets.

    “Differential effect of diet at class, order, | family, genus and OTU level; 89 taxa | (16 control; 24 PUFA; 12 SFA; 37 | sugar) contribute to differences | among diets”
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  • Findingcitation

    In ponies, a high-starch diet was associated with more reactive and less settled behavior (more pace changes, less time standing and less time investigating surroundings) than a high-fiber diet.

    “Ponies are more reactive and | less settled on high-starch | diet (↑ number of times pace | was changed, less time | standing and less time | investigating surroundings, | ponies were more tense, | nervous, unsure)”
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    Findingcitation

    In rats, a cafeteria diet decreased microbial diversity and produced deficits in a place recognition task.

    “↓ Microbial diversity (observed OTUs | and Shannon's diversity) after Caf | diet”
    • Also stated in: § Conclusions and Future Directions · plain
      “Deficits in place recognition task”
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    Findingcitation

    In mice, intermittent fasting increased α-diversity and improved spatial memory.

    “↑ α-Diversity and changes in | β-diversity”
    • Also stated in: § Conclusions and Future Directions · plain
      “↑ spatial | memory after intermittent | fasting”
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    Findingcitation

    In horses, a high-starch (HB) diet increased the concentration of total anaerobic, amylolytic and lactate-utilizing bacteria in the colon relative to a high-fiber (HF) diet, with no difference in the cecum and no difference in cellulolytic bacteria in the colon.

    “↑ Concentration of total anaerobic, | amylolytic and lactate-utilizing | bacteria in colon after HB diet (no | difference in cecum); cellulolytic | bacteria not different in colon”
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    Findingcitation

    In mice, 8 weeks of a high-fructose diet changed the microbial community structure but not α-diversity.

    “8 wk of high-fructose changed | microbial structure of community | but not α-diversity”
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    Findingcitation

    In rats, a cafeteria diet decreased α-diversity and impaired spatial recognition in a novel place recognition task, whereas a cycle cafeteria diet did not.

    “↓ Spatial recognition (novel | place recognition task) in Caf | but not cycle diet”
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    Premisecitation

    Consumption of a high-fiber diet promotes an increase in bacterial diversity and leads to a bloom in the growth of beneficial bacteria (Bifidobacterium sp., Lactobacillus sp., Akkermansia sp., Faecalibacterium sp., Roseburia sp., Bacteroides sp., and Prevotella) as well as a reduction in potentially pathogenic bacteria (e.g., Enterobacteriaceae).

    “It is generally accepted that the consumption of a highfiber diet promotes an increase in bacterial diversity and leads to a bloom in the growth of beneficial bacteria (i.e., Bifidobacterium sp., Lactobacillus sp., Akkermansia sp., Faecalibacterium sp., Roseburia sp., Bacteroides sp., and Prevotella) as well as a reduction in potentially pathogenic bacteria (e.g., Enterobacteriaceae) (63)(64)(65)(”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    Variations in macronutrient ratios, amounts, and types are large drivers of the effect on microbiota composition, with specific microbes thriving on selective macronutrients, thereby increasing their abundance.

    “Variations in macronutrient ratios, amounts, and types are large drivers of the effect on microbiota composition (111), with specific microbes thriving on selective macronutrients, thereby increasing their abundance.”
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    Premisecitation

    The core gut microbiota in adulthood is relatively stable, but environmental factors have been identified that can shape the gut microbial community.

    “The core gut microbiota in adulthood is relatively stable, but environmental factors have been identified that can shape the gut microbial community (23,35,36).”
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    Interpretationreasoning

    The study of whole-dietary approaches represents a more realistic path to the development of new dietary interventions and could inform national healthy eating guidelines and policies.

    “Thus, the study of whole-dietary approaches represents a more realistic path to the development of new dietary interventions and could inform national healthy eating guidelines and policies.”
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    Premisecitation

    Diet is one of the key factors involved in shaping the gut microbiota, having marked effects on microbial diversity, as well as the abundance and metabolic capacity of specific microbes.

    “Moreover, it has become clear that diet is one of the key factors involved in shaping the gut microbiota, having marked effects on microbial diversity, as well as the abundance and metabolic capacity of specific microbes (3)(4)(5).”
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    • cites (3)(4)(5)

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    ω-3 fatty acids have been proposed to restore the eubiotic state in pathological conditions by increasing beneficial bifidobacteria and decreasing enterobacteria, which in turn supports an anti-inflammatory environment through the production of SCFAs and suppression of endotoxemia.

    “Indeed, ω-3 fatty acids have been proposed to restore the eubiotic state in pathological conditions by increasing the beneficial bifidobacteria and decreasing enterobacteria, which in turn supports an anti-inflammatory environment through the production of SCFAs and suppression of endotoxemia (81,141).”
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    SCFAs, specifically butyrate, have been implicated in gastrointestinal and metabolic health, exert anti-inflammatory and immunomodulatory properties, and can influence central functioning.

    “SCFAs, specifically butyrate, have been implicated in gastrointestinal (main energy source of colonocytes, supporting gut barrier function) and metabolic (glucose homeostasis, lipid oxidation) health, exert anti-inflammatory and immunomodulatory properties, and can influence central functioning (as outlined in detail below) (119, 120).”
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    Medium-chain fatty acids increase the abundance of Bifidobacterium, Bacteroides, and Prevotella and decrease the abundance of Clostridium histolyticum or Helicobacter in animal studies.

    “Results from animal studies show that medium-chain fatty acids (7-12 carbons) increase the abundance of Bifidobacterium, Bacteroides, and Prevotella and decrease the abundance of Clostridium histolyticum or Helicobacter (119, 124-126).”
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    High SFA intake is associated with reduction in total bacterial abundance in humans and in microbial diversity and richness, as well as an increase in proinflammatory bacteria (e.g., Bilophila wadsworthia) in mice.

    “For example, high SFA intake has been shown to be associated with reduction in total bacterial abundance in humans (95) and in microbial diversity and richness (95,96), as well as an increase in proinflammatory bacteria (e.g., Bilophila wadsworthia) (96)(97)(98) in mice.”
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    Premisecitation

    In humans, healthier polyunsaturated fatty acids (e.g., omega-3 PUFAs) promote the growth of beneficial bacteria, including butyrate producers such as Lactobacillus, Lachnospira, Roseburia, and Bifidobacterium, and are correlated with higher microbial diversity as well as taxa from the families Lachnospiraceae and Ruminococcaceae.

    “In humans, healthier polyunsaturated fatty acids (e.g., omega-3 PUFAs) promote the growth of beneficial bacteria, including butyrate producers such as Lactobacillus, Lachnospira, Roseburia, and Bifidobacterium (81), and are correlated with higher microbial diversity as well as taxa from the families Lachnospiraceae and Ruminococcaceae (82).”
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    Premisecitation

    ω-3 fatty acids have benefits for central functioning ranging from enhanced memory, mood, attention, and cognitive performance to a reduced risk of developing depression and regulation of stress sensitivity.

    “The benefits of ω-3 (n-3) fatty acids for central functioning range from enhanced memory, mood, attention, and cognitive performance to a reduced risk of developing depression and regulation of stress sensitivity (131-138).”
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    Premisecitation

    Nonnutritive sweeteners have been linked to detrimental effects on microbial diversity and composition and decreased butyrate concentration, but evidence is inconsistent, with some reports concluding no clear effects or that only some sweeteners impact the microbial profile.

    “Although earlier human studies indicated detrimental effects on microbial diversity and composition (99, 100) and a more recent study linked consumption of nonnutritive sweeteners to a “dysbiosis” [an increasingly redundant term in microbiome research (171)] and a decrease in butyrate concentration (172), some reports have concluded that no clear effects of sweeteners on the microbiota can be”
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    Several human and animal studies have indicated that consumption of fruit and vegetables leads to increased microbial diversity and function, a shift in the abundance of bacterial phyla, growth of beneficial bacteria, such as Bifidobacterium and Lactobacillus, and reduction in potentially harmful bacteria, including E. coli and Enterococcus.

    “Several human and animal studies have indicated that consumption of fruit and vegetables leads to increased microbial diversity and function, a shift in the abundance of bacterial phyla, growth of beneficial bacteria, such as Bifidobacterium and Lactobacillus, and reduction in potentially harmful bacteria, including E. coli and Enterococcus (51)(52)(53)(54)(55).”
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    Premisecitation

    A recent systematic review and meta-analysis of randomized controlled trials concluded that nut consumption shapes the microbiota at the genus level (e.g., increases in Clostridium, Dialister, Roseburia, and Lachnospira, decrease in Parabacteroides); however, the specific effects depend on the type and amount of nut consumed and the duration of the intervention.

    “A recent systematic review and meta-analysis of randomized controlled trials on the effect of nut consumption on gut microbiota concluded that nut consumption shapes the microbiota at the genus level (e.g., increases in Clostridium, Dialister, Roseburia, and Lachnospira, decrease in Parabacteroides); however, the specific effects depend on the type and amount of nut consumed and the duration of”
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    Iron supplementation in a cohort of Kenyan children increased the abundance of pathogens such as Bacillus cereus, Staphylococcus aureus, Clostridium difficile, C. perfringens, and Salmonella, potentially contributing to gut inflammation.

    “For example, iron supplementation in a cohort of Kenyan children increased the abundance of pathogens such as Bacillus cereus, Staphylococcus aureus, Clostridium difficile, C. perfringens, and Salmonella, potentially contributing to gut inflammation (156)”
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    Premisecitation

    Switching to a high-protein, low-carbohydrate diet reduces the abundance of butyrate-producing bacteria and increases colonic protein fermentation and metabolites detrimental to health, such as branched-chain fatty acids and concentrations of phenylacetic acid and N-nitroso compounds.

    “Switching to a high-protein, low-carbohydrate diet reduces the abundance of butyrate-producing bacteria and increases colonic protein fermentation and metabolites detrimental to health, such as branched-chain fatty acids (BCFAs) and concentrations of phenylacetic acid and Nnitroso compounds (121).”
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    Premisecitation

    In humans, consumption of a fermented dairy drink for 4 weeks increased the abundance of a few specific genera and enriched some functions of the resident microbes.

    “In another recent human study, consumption of a fermented dairy drink for 4 wk increased the abundance of a few specific genera (e.g., Holdemania, Gordonibacter, Lactobacillus, an unclassified Mollicutes (RF-9), and two unclassified genera from Clostridiales), and enriched some functions of the resident microbes (195).”
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    A recent systematic review concluded that significant changes can be observed after pulse consumption, but that results are inconsistent, especially in humans.

    “A recent systematic review concluded that significant changes can be observed after pulse consumption, but that results are inconsistent, especially in humans (185).”
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    Premisecitation

    Emulsifier consumption by germ-free animals and animals with a highly restricted microbiota did not elicit the same detrimental health effects, suggesting that microbial modulation may be required for the adverse effects of emulsifiers on host health.

    “Importantly, it has been shown that emulsifier consumption by germ-free (GF) animals (107) and animals with a highly restricted microbiota (180) did not elicit the same detrimental health effects, suggesting that microbial modulation may be required for the adverse effects of emulsifiers on host health.”
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    Premisecitation

    A recent systematic review suggests that vitamin D status or supplementation can modulate microbiota composition, but with inconsistent data, especially from human studies, no trend is emerging yet.

    “A recent systematic review summarizing the evidence available from human and animal studies on the impact of vitamin D on the gut microbiota suggests that vitamin D status or supplementation can modulate microbiota composition; but with inconsistent data, especially from human studies, no trend is emerging yet (147).”
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    Premisecitation

    An 8 wk intervention with 56.7 g of almonds in young adults revealed an increase in α-diversity measures and a decrease in B. fragilis abundance.

    “On the other hand, an 8 wk intervention with 56.7 g of almonds in young adults revealed an increase in α-diversity measures and a decrease in B. fragilis abundance (62).”
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    Premisecitation

    Polyphenols display a prebiotic-like effect, increasing the growth of beneficial bacterial strains, such as bifidobacteria and lactobacilli, while reducing the number of potential pathogens, such as C. perfringens and C. histolyticum in a dose-dependent manner.

    “Polyphenols display a “prebioticlike” effect, increasing the growth of beneficial bacterial strains, such as bifidobacteria and lactobacilli, while reducing the number of potential pathogens, such as C. perfringens and C. histolyticum in a dose-dependent manner (83,84).”
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    Premisecitation

    In mice, animal-based protein increases potential detrimental gut microbes, and plant-based protein boosts the abundance of Bifidobacterium, Roseburia, and Lactobacillus and lowers the abundance of pathogens such as Bacteroides fragilis and Clostridium perfringens.

    “In mice, animal-based protein increases potential detrimental gut microbes, e.g., Peptostreptococcaceae, Ruminococcaceae, Enterococcus, Streptococcus, Turicibacter, or Escherichia (92), and plant-based protein boosts the abundance of Bifidobacterium, Roseburia, and Lactobacillus and lowers the abundance of pathogens such as Bacteroides fragilis and Clostridium perfringens (37,42,80).”
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    Premisecitation

    In a recent human intervention study, flavonoid-rich orange juice reduced depressive symptoms significantly compared with flavonoid-low orange cordial and enriched bacterial genera belonging to the Lachnospiraceae, Bifidobacteriaceae, and Bacteroidaceae families.

    “In a recent human intervention study, flavonoid-rich orange juice reduced depressive symptoms significantly compared with flavonoid-low orange cordial and enriched bacterial genera belonging to the Lachnospiraceae, Bifidobacteriaceae, and Bacteroidaceae families (167).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Park, 2020, Flavonoid-rich orange juice intake and altered gut microbiome in young adults with depressive symptom: a randomized controlled study, Nutrients source

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  • May combine two claims.

    Premisecitation

    In mice, kefir administration increased the abundance of L. reuteri, Eubacterium plexicaudatum, and Bifidobacterium pseudolongum, decreased Lachnospiraceae bacterium 3_1_46FAA, Propionibacterium acnes, and Bacillus amyloliquefaciens, and shifted the functional potential of the gut microbiota toward production of neuroactive metabolites.

    “In a recent mouse study, kefir administration increased the abundance of L. reuteri, Eubacterium plexicaudatum, and Bifidobacterium pseudolongum, and decreased Lachnospiraceae bacterium 3_1_46FAA, Propionibacterium acnes, and Bacillus amyloliquefaciens, and shifted the functional potential of the gut microbiota toward the production of neuroactive metabolites (58).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] van de Wouw, 2020, Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse, Microbiome source

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  • May combine two claims.

    Premisecitation

    The gut microbiota can synthesize certain vitamins, most notably vitamin K and B-group vitamins, some of which might be directly absorbed.

    “It is well appreciated that the gut microbiota can synthesize certain vitamins, most notably vitamin K and B-group vitamins [e.g., cobalamin (B 12 ), folate, and riboflavin (144, 145)], some of which might be directly absorbed.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [144] Hill, 1997, Intestinal flora and endogenous vitamin synthesis, Eur J Cancer Prev source

      Not checked in the free run.

    • cites [145] Rowland, 2018, Gut microbiota functions: metabolism of nutrients and other food components, Eur J Nutr source

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  • May combine two claims.

    Premisecitation

    In mice, navy bean and black bean flours increased the abundance of Prevotella, S24-7, and Ruminococcus flavefaciens and SCFA production, and decreased the abundance of Ruminococcus gnavus, Oscillospira, Coprococcus, Lactococcus, Streptococcus, Coprobacillus, Parabacteroides, Adlercreutzia, and others compared with the basal diet.

    “In mice, navy bean and black bean flours increased the abundance of Prevotella, S24-7, and Ruminococcus flavefaciens and SCFA production, and decreased the abundance of Ruminococcus gnavus, Oscillospira, Coprococcus, Lactococcus, Streptococcus, Coprobacillus, Parabacteroides, Adlercreutzia, and others compared with the basal diet.Some bean-specific changes were also observed, with black bean flour”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188] Monk, 2017, Navy and black bean supplementation primes the colonic mucosal microenvironment to improve gut health, J Nutr Biochem source

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  • May combine two claims.

    Premisecitation

    Fermented soybean milk resulted in a decrease in coliform organisms and C. perfringens as well as increases in Bifidobacterium and Lactobacillus.

    “fermented soybean milk resulted in a decrease in coliform organisms and C. perfringens as well as increases in Bifidobacterium and Lactobacillus (57).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Cheng, 2005, Effect of fermented soy milk on the intestinal bacterial ecosystem, World J Gastroenterol source

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  • May combine two claims.

    Premisecitation

    High-fat diets in animal studies reproducibly change gut microbial community structure, decreasing overall microbiota diversity and beneficial bacteria and increasing the Firmicutes:Bacteroidetes ratio and abundance of Enterobacteriales, Clostridium cluster XVIa, Mollicutes, and B. wadsworthia.

    “Similar to the Western diet, high-fat diets in animal studies reproducibly change gut microbial community structure, decreasing the overall microbiota diversity and beneficial bacteria (e.g., A. muciniphila, Bifidobacterium, Lactobacillus, and Lactococcus) and increasing the Firmicutes:Bacteroidetes ratio and the abundance of Enterobacteriales, Clostridium cluster XVIa, Mollicutes, and B. wadswort”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [90] Hildebrandt, 2009, High-fat diet determines the composition of the murine gut microbiome independently of obesity, Gastroenterology source

      Not checked in the free run.

    • cites [91] Bisanz, 2019, Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet, Cell Host Microbe source

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    • cites [206] Turnbaugh, 2009, The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice, Sci Transl Med source

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  • May combine two claims.

    Premisecitation

    Greater microbial diversity and higher abundance of health-promoting bacterial taxa are associated with consumption of the Mediterranean diet.

    “Greater microbial diversity as well as higher abundance of health-promoting bacterial taxa (i.e., Clostridium cluster XIVa, F. prausnitzii, Roseburia, Eubacterium, B. thetaiotaomicron, Parabacteroides distasonis, Bifidobacterium adolescentis, and Bifidobacterium longum) have been associated with consumption of the Mediterranean diet (38)(39)(40).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [38] Jin, 2019, Metabolomics and microbiomes as potential tools to evaluate the effects of the Mediterranean diet, Nutrients source

      Not checked in the free run.

    • cites [39] Gutierrez-Diaz, 2016, Mediterranean diet and faecal microbiota: a transversal study, Food Funct source

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    • cites [40] Meslier, 2020, Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ultraprocessed food components are detrimental to the microbiota and some studies have described consequences of ultraprocessed food consumption for gut microbial composition.

    “These food components are detrimental to the microbiota and some studies have described consequences of ultraprocessed food consumption for gut microbial composition (208).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [208] Lane, 2020, The effect of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity: a systematic literature review, Obes Res Clin Pract source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Firmicutes and Proteobacteria were more abundant in Italian children, with overrepresentation of Enterobacteriaceae such as Shigella and Escherichia.

    “On the other hand, Firmicutes and Proteobacteria were more abundant in Italian children, with an overrepresentation of Enterobacteriaceae (e.g., Shigella and Escherichia).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] De Filippo, 2010, Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa, Proc Natl Acad Sci U S A source

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  • May combine two claims.

    Premisecitation

    A small pilot crossover study in humans showed a detrimental impact on the gut microbiota and associated metabolites within 4 days of adopting a Western-style diet, with increases in bile-tolerant microbes, including Collinsella, Parabacteroides, and B. wadsworthia, as well as increases in TMAO and decreases in indole-3-lactic acid and indole-3-propionic acid.

    “More recently, a small pilot crossover study in humans showed a detrimental impact on the gut microbiota and associated metabolites within 4 d of adopting a Westernstyle diet, with increases in bile-tolerant microbes, including Collinsella, Parabacteroides, and B. wadsworthia, as well as increases in TMAO and decreases in the metabolites indole-3-lactic acid and indole-3-propionic acid (205).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [205] Zhu, 2020, Human gut microbiome composition and tryptophan metabolites were changed differently by fast food and Mediterranean diet in four days: a pilot study, Nutr Res source

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  • May combine two claims.

    Premisecitation

    Characteristic patterns in the gut microbiota for plant-based diets include high bacterial richness, increased numbers of Bifidobacterium, Lactobacillus, Ruminococcus, Eubacterium rectale, Roseburia, Prevotella, F. prausnitzii, and Anaerostipes, but lower abundance of Clostridium sensu stricto, C. perfringens, C. histolyticum, and Odoribacter.

    “Thus, characteristic patterns in the gut microbiota for these types of diets include high bacterial richness, increased numbers of Bifidobacterium, Lactobacillus, Ruminococcus, Eubacterium rectale, Roseburia, Prevotella, F. prausnitzii, and Anaerostipes, but lower abundance of Clostridium sensu stricto, C. perfringens, C. histolyticum, and Odoribacter (42,(45)(46)(47)(48)(49).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [42] Tomova, 2019, The effects of vegetarian and vegan diets on gut microbiota, Front Nutr source

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    • cites [45] Liszt, 2009, Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting, Ann Nutr Metab source

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    • cites [46] Losasso, 2018, Assessing the influence of vegan, vegetarian and omnivore oriented westernized dietary styles on human gut microbiota: a cross sectional study, Front Microbiol source

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  • May combine two claims.

    Premisecitation

    Members of the Lachnospiraceae family, Ruminococcus, and Bacteroides were negatively associated with processed food groups, whereas Lachnospiraceae (Fusicatenibacter saccharivorans), Blautia, and Clostridium were positively associated with processed food consumption in children.

    “For example, members of the Lachnospiraceae family (related to Clostridium clostridioforme, C. bolteae, C. celerecrescens, or C. sphenoides), Ruminococcus, and Bacteroides were negatively associated with processed food groups (e.g., processed meat and savory snacks), whereas Lachnospiraceae (Fusicatenibacter saccharivorans), Blautia, and Clostridium were positively associated with processed food”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [210] Matsuyama, 2019, Dietary intake influences gut microbiota development of healthy Australian children from the age of one to two years, Sci Rep source

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  • May combine two claims.

    Premisecitation

    Long-term consumption of a Western diet in humans and animals can lead to extinction of beneficial microbes, decrease bacterial diversity, and drive the microbiota to a predominant Bacteroides-driven enterotype.

    “Long-term consumption of a Western diet in humans and animals can lead to the extinction of beneficial microbes, decrease bacterial diversity, and drive the microbiota to a predominant Bacteroides-driven enterotype (13,14,116,88).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13] Sonnenburg, 2016, Diet-induced extinctions in the gut microbiota compound over generations, Nature source

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    • cites [14] Vangay, 2018, US immigration westernizes the human gut microbiome, Cell source

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    • cites [116] Precup, 2019, Gut Prevotella as a possible biomarker of diet and its eubiotic versus dysbiotic roles: a comprehensive literature review, Br J Nutr source

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  • May combine two claims.

    Premisecitation

    An increased Firmicutes:Bacteroidetes ratio and decreases in protective SCFA-producing bacteria such as F. prausnitzii are often observed.

    “Likewise, an increased Firmicutes:Bacteroidetes ratio (41) and decreases in protective SCFA-producing bacteria (e.g., F. prausnitzii) (89, 204) are often observed.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [41] De Filippis, 2016, High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome, Gut source

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    • cites [89] Agus, 2016, Western diet induces a shift in microbiota composition enhancing susceptibility to adherent-invasive E. coli infection and intestinal inflammation, Sci Rep source

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    • cites [204] Ganesan, 2018, Causal relationship between diet-induced gut microbiota changes and diabetes: a novel strategy to transplant Faecalibacterium prausnitzii in preventing diabetes, Int J Mol Sci source

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  • May combine two claims.

    Premisecitation

    Generally favorable microbial patterns have been observed for plant-based diets, although the specific microbial composition depends on the degree of adherence.

    “Although the specific microbial composition depends on the degree of adherence to a plant-based diet, generally favorable microbial patterns have been observed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Children in Burkina Faso had a microbial profile specialized for indigestible polysaccharide metabolism, enriched in Bacteroidetes and Actinobacteria, with Prevotella, Xylanibacter, and Treponema exclusively represented compared with children from Italy.

    “More specifically, these children had a microbial profile specialized for indigestible polysaccharide metabolism, enriched in Bacteroidetes and Actinobacteria, with Prevotella, Xylanibacter, and Treponema exclusively represented in their microbiota compared with children from Italy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] De Filippo, 2010, Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    During the prenatal period, maternal factors, including diet, not only influence the offspring's microbial profile but may also exert lasting effects on infant cognition and behavior.

    “During the prenatal period, maternal factors, including diet, not only influence the offspring's microbial profile but may also exert lasting effects on infant cognition and behavior.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Animal studies have demonstrated that administration of probiotics such as Lactobacillus plantarum, L. rhamnosus, and B. longum can have anxiolytic and antidepressive effects and can impact aspects of cognitive function.

    “Animal studies have demonstrated that administration of probiotics (e.g., Lactobacillus plantarum, L. rhamnosus, B. longum) can have anxiolytic and antidepressive effects (222, 223) and can impact aspects of cognitive function (224).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [222] Abildgaard, 2017, Probiotic treatment reduces depressive-like behaviour in rats independently of diet, Psychoneuroendocrinology source

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    • cites [223] Barros-Santos, 2020, Effects of chronic treatment with new strains of Lactobacillus plantarum on cognitive, anxiety- and depressive-like behaviors in male mice, PLoS One source

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    • cites [224] Ni, 2019, Lactobacillus and Bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of gut microbiota, Mol Nutr Food Res source

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    Interpretationnone given

    Establishing direct links between the gut microbiota and brain function in humans is more difficult and of a correlational nature.

    “Establishing direct links between the gut microbiota and brain function in humans is more difficult and of correlational nature.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the first years of life the microbial community is dynamic and some bacteria that become part of the adult microbiota already colonize the gut during the first months of life.

    “Especially in the first years of life the microbial community is dynamic and some bacteria that become part of the adult microbiota already colonize the gut during the first months of life (230-232).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [230] Bergstrom, 2014, Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants, Appl Environ Microbiol source

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    • cites [231] Jost, 2015, Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health, Nutr Rev source

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    • cites [232] Hill, 2017, Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort, Microbiome source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In nonhuman primates, an unhealthy diet during pregnancy has been linked to poorer cognitive outcomes, enhanced stress responses, and behavioral disruptions in the offspring.

    “Likewise, in nonhuman primates, an unhealthy diet during pregnancy has been linked to poorer cognitive outcomes, enhanced stress responses, and behavioral disruptions in the offspring (242),”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [242] Sullivan, 2014, Maternal high fat diet consumption during the perinatal period programs offspring behavior, Physiol Behav source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Another recent meta-analysis and systematic review concluded that current evidence from human trials does not support the efficacy of probiotics, prebiotics, and fermented food in affecting cognitive function, although the quality and quantity of available data limit firm conclusions.

    “On the other hand, another recent meta-analysis and systematic review concluded that the current evidence from human trials does not support the efficacy of probiotics, prebiotics, and fermented food in affecting cognitive function, although the quality and quantity of the available data limit firm conclusions (229);”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [229] Marx, 2020, Prebiotics, probiotics, fermented foods and cognitive outcomes: a meta-analysis of randomized controlled trials, Neurosci Biobehav Rev source

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  • May combine two claims.

    Premisecitation

    There is a lack of studies investigating the same strain of probiotic or type of prebiotic, and probiotic- and prebiotic-specific effects are often observed.

    “for example, there is lack of studies investigating the same strain of probiotic or type of prebiotic, and probiotic-and prebiotic-specific effects are often observed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [229] Marx, 2020, Prebiotics, probiotics, fermented foods and cognitive outcomes: a meta-analysis of randomized controlled trials, Neurosci Biobehav Rev source

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  • May combine two claims.

    Premisecitation

    Prebiotic human milk oligosaccharides can be fermented by resident microbes, promoting the growth of beneficial bacteria.

    “Additionally, prebiotic human milk oligosaccharides (HMOs) can be fermented by the resident microbes, promoting the growth of beneficial bacteria (260).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [260] Bode, 2012, Human milk oligosaccharides: every baby needs a sugar mama, Glycobiology source

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  • May combine two claims.

    Premisecitation

    In human studies, early introduction of solid food was associated with a higher risk of obesity or immunological diseases.

    “In human studies, early introduction of solid food was associated with a higher risk of obesity (274, 275) or immunological diseases (276).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [274] Pluymen, 2018, Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study, Eur J Nutr source

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    • cites [275] Differding, 2020, Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI, Pediatr Obes source

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    • cites [276] Nwaru, 2013, Timing of infant feeding in relation to childhood asthma and allergic diseases, J Allergy Clin Immunol source

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  • May combine two claims.

    Premisecitation

    At birth, neonates are exposed to the first large number of microbes that colonize the gastrointestinal tract and differences in the microbiota composition based on birth mode have been reported.

    “At birth, neonates are exposed to the first large number of microbes that colonize the gastrointestinal tract and differences in the microbiota composition based on birth mode have been reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Following birth, colonization of the infant gut is majorly determined by the early feeding mode, with distinguishable microbial compositions between breast- and formula-fed infants.

    “Following birth, colonization of the infant gut is majorly determined by the early feeding mode, with distinguishable microbial compositions between breast-and formula-fed infants (254, 255).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [254] Ku, 2020, Microbiome study of initial gut microbiota from newborn infants to children reveals that diet determines its compositional development, J Microbiol Biotechnol source

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    • cites [255] Matsuyama, 2019, Breastfeeding: a key modulator of gut microbiota characteristics in late infancy, J Dev Orig Health Dis source

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  • May combine two claims.

    Premisecitation

    Naturally born infants are exposed to the mother's vaginal bacteria, whereas babies born by C-section are first introduced to bacteria of the mother's skin, the hospital environment, or the healthcare workers.

    “Thus, naturally born infants are exposed to the mother's vaginal bacteria, whereas babies born by C-section are first introduced to bacteria of the mother's skin, the hospital environment, or the healthcare workers (237).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [237] Dominguez-Bello, 2010, Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns, Proc Natl Acad Sci U S A source

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  • May combine two claims.

    Premisecitation

    Animal studies have shown that early exposure to microbes is essential for neurodevelopment and that some behavioral effects related to a missing or altered microbiota cannot be reversed later in life or can only be reversed during a specific period of time.

    “Animal studies have shown that this early exposure to microbes is essential for neurodevelopment and that some behavioral effects related to a missing or altered microbiota cannot be reversed later in life or can only be reversed during a specific period of time (218, 245, 252).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [218] Sudo, 2004, Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice, J Physiol source

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    • cites [245] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source

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    • cites [252] Clarke, 2013, The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner, Mol Psychiatry source

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  • May combine two claims.

    Premisecitation

    Supplementation with oligosaccharides from birth in a mouse model modulated microbiota composition and diversity, increased saccharolytic and decreased proteolytic fermentation while also resulting in improved social and anxiety-like behavior.

    “Supplementation with oligosaccharides from birth in a mouse model modulated the microbiota composition and diversity, increased saccharolytic and decreased proteolytic fermentation while also resulting in improved social and anxiety-like behavior (268),”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [268] Szklany, 2020, Supplementation of dietary non-digestible oligosaccharides from birth onwards improve social and reduce anxiety-like behaviour in male BALB/c mice, Nutr Neurosci source

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  • May combine two claims.

    Premisecitation

    In piglets, early weaning stress impairs intestinal barrier function and increases inflammation and oxidative stress.

    “In piglets, early weaning stress impairs intestinal barrier function (271) and increases inflammation (272) and oxidative stress (273).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [271] Moeser, 2017, Weaning stress and gastrointestinal barrier development: implications for lifelong gut health in pigs, Anim Nutr source

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    • cites [272] Pie, 2004, Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets, J Nutr source

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    • cites [273] Yin, 2014, Development of an antioxidant system after early weaning in piglets, J Anim Sci source

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  • May combine two claims.

    Interpretationcitation

    Some microbial and behavioral alterations associated with C-section could be reversed by supplementation with a prebiotic mixture (galactooligosaccharide, fructooligosaccharide), suggesting that microbiota-targeted diet interventions could be used to alleviate some of the negative effects associated with C-section.

    “however, some of these microbial and behavioral alterations could be reversed by supplementation with a prebiotic mixture (galactooligosaccharide, fructooligosaccharide), suggesting that microbiota-targeted diet interventions could be used to alleviate some of the negative effects associated with Csection (251).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [251] Morais, 2020, Enduring behavioral effects induced by birth by caesarean section in the mouse, Curr Biol source

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  • May combine two claims.

    Premisecitation

    Human milk harbors a unique microbial community, including commensal, mutualistic, and probiotic bacteria, some of which can be found as first colonizers of the neonatal gut.

    “Human milk harbors a unique microbial community, including commensal, mutualistic, and probiotic bacteria, some of which can be found as first colonizers of the neonatal gut (258, 259).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [258] Cabrera-Rubio, 2012, The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery, Am J Clin Nutr source

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    • cites [259] Solis, 2010, Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut, Anaerobe source

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  • May combine two claims.

    Premisecitation

    Generally, breast-fed infants harbor a less diverse and species-rich microbiota dominated by Bifidobacterium species, whereas the microbiota of formula-fed infants is functionally more similar to that of an adult and is often enriched in microbial taxa such as Klebsiella, Enterococcus, Peptostreptococcaceae, Akkermansia, Veillonella, and C. difficile.

    “Generally, breast-fed infants harbor a less diverse and species-rich microbiota that is dominated by Bifidobacterium species, whereas the microbiota of formulafed infants is functionally more similar to that of an adult and is often enriched in microbial taxa such as Klebsiella, Enterococcus, Peptostreptococcaceae, Akkermansia, Veillonella, and C. difficile (256, 257).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [256] Vandenplas, 2020, Factors affecting early-life intestinal microbiota development, Nutrition source

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    • cites [257] Davis, 2017, The role of early life nutrition in the establishment of gastrointestinal microbial composition and function, Gut Microbes source

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  • May combine two claims.

    Premisecitation

    Altering the timing of weaning could result in a pathological imprinting of the immune response and increased susceptibility to later immunopathologies.

    “Altering the timing of weaning could result in a pathological imprinting of the immune response and increased susceptibility to later immunopathologies (270).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [270] Al Nabhani, 2019, A weaning reaction to microbiota is required for resistance to immunopathologies in the adult, Immunity source

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  • May combine two claims.

    Premisecitation

    Although differences can dissipate a few weeks or months after birth, it has been suggested that some microbes acquired during the first years of life will be important residents of the adult microbiota.

    “Although these differences can dissipate a few weeks or months after birth (248), it has been suggested that some microbes acquired during the first years of life will be important residents of the adult microbiota (249).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [248] Chu, 2017, Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery, Nat Med source

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    • cites [249] Litvak, 2019, The founder hypothesis: a basis for microbiota resistance, diversity in taxa carriage, and colonization resistance against pathogens, PLoS Pathog source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Accelerated maturation of the gut microbiota has been proposed as a contributing pathway to the detrimental effects of early weaning on host processes.

    “Due to the known profound effects of the microbiota on host development, accelerated maturation of the gut microbiota has been proposed as a contributing pathway to the detrimental effects of early weaning on host processes (275).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [275] Differding, 2020, Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI, Pediatr Obes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These associations are observed across the age range, including in early adolescence, which represents the primary age of onset for mental disorders.

    “These associations are observed across the age range, including in early adolescence, which represents the primary age of onset for mental disorders (292, 310).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [292] Jacka, 2010, Associations between diet quality and depressed mood in adolescents: results from the Australian Healthy Neighbourhoods Study, Aust N Z J Psychiatry source

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    • cites [310] Jacka, 2011, A prospective study of diet quality and mental health in adolescents, PLoS One source

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  • May combine two claims.

    Premisecitation

    Adolescence is a critical time period for neuroanatomical change and maturation, which translates into behavioral development, including cognitive function, social cognition, and executive function.

    “Adolescence is also a critical time period for neuroanatomical change and maturation, which translates into behavioral development, including cognitive function, social cognition, and executive function (285, 286).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [285] Blakemore, 2006, Development of the adolescent brain: implications for executive function and social cognition, J Child Psychol Psychiatry source

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    • cites [286] Burnett, 2011, The social brain in adolescence: evidence from functional magnetic resonance imaging and behavioural studies, Neurosci Biobehav Rev source

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  • May combine two claims.

    Premisecitation

    In a mouse model of adolescence, exposure to a cafeteria diet for 21 days resulted in decreased species evenness and abundance of Roseburia, Turicibacter, and Enterorhabdus, and altered gene expression involved in neuroimmunity and neurotransmission in the prefrontal cortex and amygdala, although no behavioral manifestations were observed.

    “In a mouse model of adolescence, exposure to a cafeteria diet for 21 d resulted in decreased species evenness (measured by the Shannon diversity index) and abundance of Roseburia, Turicibacter, and Enterorhabdus, and, although no behavioral manifestations were observed, altered gene expression involved in neuroimmunity and neurotransmission in the prefrontal cortex and amygdala (294).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [294] Fulling, 2020, Adolescent dietary manipulations differentially affect gut microbiota composition and amygdala neuroimmune gene expression in male mice in adulthood, Brain Behav Immun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Supplementing children with moderate acute malnutrition with a microbiota-directed complementary food prototype shifted the microbiota as well as markers of neurodevelopment toward that of healthy children, indicating that the immature microbiota is causally linked to unhealthy growth and development, but can be rescued by microbiota-targeted food therapy.

    “Supplementing children with moderate acute malnutrition with a microbiota-directed complementary food prototype shifted the microbiota as well as markers of neurodevelopment toward that of healthy children, indicating that the immature microbiota is causally linked to unhealthy growth and development, but can be rescued by microbiota-targeted food therapy (282).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [282] Gehrig, 2019, Effects of microbiota-directed foods in gnotobiotic animals and undernourished children, Science source

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  • May combine two claims.

    Premisecitation

    Unhealthy eating or dieting with failure to meet recommended intake of fruits and vegetables and excess intake of fat or high-sugar foods and drinks can be characteristic of the adolescent period.

    “Unhealthy eating or dieting with failure to meet recommended intake of fruits and vegetables and excess intake of fat or high-sugar foods and drinks can be characteristic of the adolescent period (288-290).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [288] Larson, 2007, Trends in adolescent fruit and vegetable consumption, 1999-2004: project EAT, Am J Prev Med source

      Not checked in the free run.

    • cites [289] Moreno, 2010, Trends of dietary habits in adolescents, Crit Rev Food Sci Nutr source

      Not checked in the free run.

    • cites [290] Schneider, 2000, International trends in adolescent nutrition, Soc Sci Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Animal studies demonstrated that early exposure to some dietary components shifted the microbiota composition, which could favor systemic inflammation and influence the brain, such as altering blood-brain barrier permeability.

    “Indeed, animal studies demonstrated that early exposure to some dietary components shifted the microbiota composition, which could favor systemic inflammation and influence the brain, such as altering blood-brain barrier (BBB) permeability (277).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [277] Marungruang, 2018, Impact of dietary induced precocious gut maturation on cecal microbiota and its relation to the blood-brain barrier during the postnatal period in rats, Neurogastroenterol Motil source

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  • May combine two claims.

    Premisecitation

    In general, microbial diversity decreases and numbers of beneficial bacteria reduce, whereas facultative anaerobes and opportunists or even proinflammatory pathogenic bacteria increase when compared with younger individuals.

    “In general, microbial diversity decreases and numbers of beneficial bacteria (bifidobacteria, lactobacilli, Clostridium cluster XIVa, F. prausnitzii) reduce, whereas facultative anaerobes and opportunists or even proinflammatory pathogenic bacteria (Escherichia spp., Enterobacteriaceae spp., Bacteroides spp., C. difficile, etc.) increase when compared with younger individuals (235, 295, 296).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [235] Nagpal, 2018, Gut microbiome and aging: physiological and mechanistic insights, Nutr Healthy Aging source

      Not checked in the free run.

    • cites [295] Salazar, 2017, Nutrition and the gut microbiome in the elderly, Gut Microbes source

      Not checked in the free run.

    • cites [296] Askarova, 2020, The links between the gut microbiome, aging, modern lifestyle and Alzheimer's disease, Front Cell Infect Microbiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While effects of probiotics and prebiotics on the microbiota and mood or cognition have been more widely studied, investigations into whole-food and diet approaches are scarce.

    “While the effects of probiotics and prebiotics on the microbiota and mood or cognition have been more widely studied (12), investigations into whole-food and diet approaches are scarce.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Long-Smith, 2020, Microbiota-gut-brain axis: new therapeutic opportunities, Annu Rev Pharmacol Toxicol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Poor dietary habits such as the Western-style diet, intake of low-quality, processed, or high-fat/sugar foods, and malnutrition can be related to poorer mental health, impaired cognitive function, and increased risk of developing anxiety, depression, or other mental illnesses.

    “On the other hand, poor dietary habits (such as the Westernstyle diet), intake of low-quality, processed, or high-fat/sugar foods and malnutrition (over-and undernutrition) can be related to poorer mental health (305, 306), impaired cognitive function (298), and increased risk of developing anxiety (307), depression (292, 308, 309), or other mental illnesses.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [305] O'Neil, 2014, Relationship between diet and mental health in children and adolescents: a systematic review, Am J Public Health source

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    • cites [306] Lai, 2014, A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults, Am J Clin Nutr source

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    • cites [298] Sarris, 2015, Nutritional medicine as mainstream in psychiatry, Lancet Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While some evidence from preclinical studies shows the triangular relation between diet, microbiota, and brain/behavior, similar studies in human populations are lacking and most clinical studies investigating the effect of diet on anxiety, depression or cognition did not explore microbiota compositional changes.

    “While some evidence from preclinical studies shows the triangular relation between diet, microbiota, and brain/behavior, similar studies in human populations are lacking and most clinical studies investigating the effect of diet on anxiety, depression or cognition did not explore microbiota compositional changes (199, 311, 312).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [199] Jacka, 2017, A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial), BMC Med source

      Not checked in the free run.

    • cites [311] Parletta, 2019, A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: a randomized controlled trial (HELFIMED), Nutr Neurosci source

      Not checked in the free run.

    • cites [312] Martinez-Lapiscina, 2013, Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial, J Neurol Neurosurg Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These extended maturations can pose an additional sensitive period for microbial priming of the maturing adolescent brain and provide opportunities to improve adolescent mental wellbeing.

    “These extended maturations can pose an additional sensitive period for microbial priming of the maturing adolescent brain and provide opportunities to improve adolescent mental wellbeing (219, 287).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [219] Cowan, 2020, Annual Research Review: Critical windows – the microbiota-gut-brain axis in neurocognitive development, J Child Psychol Psychiatr source

      Not checked in the free run.

    • cites [287] Neufeld, 2016, What’s bugging your teen?—The microbiota and adolescent mental health, Neurosci Biobehav Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Transfer of fecal samples from undernourished children to germ-free mice elicited metabolic and immune dysregulations in the mouse model similar to those observed in the human host, suggesting that manifestations of malnutrition could in part be attributed to the absence of certain beneficial microbes.

    “Transfer of fecal samples from undernourished children to GF mice elicited metabolic and immune dysregulations in the mouse model similar to those observed in the human host, suggesting that the manifestations of malnutrition could in part be attributed to the absence of certain beneficial microbes (280).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [280] Smith, 2013, Gut microbiomes of Malawian twin pairs discordant for kwashiorkor, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Traditional dietary patterns from many parts of the world, such as the Norwegian and Japanese diets, also show protective associations and are correlated with reduced risk of developing depression or Alzheimer's disease as well as a general slowing of cognitive decline.

    “Although the Mediterranean diet is the dietary pattern most studied in regard to health outcomes, including mental health (201), traditional dietary patterns from many parts of the world (e.g., the Norwegian and Japanese diets) also show protective associations (302, 303) and are correlated with reduced risk of developing depression or Alzheimer's disease as well as a general slowing of cognitive”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [302] Munoz, 2008, Adherence to the Mediterranean diet is associated with better mental and physical health, Br J Nutr source

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    • cites [303] Opie, 2017, Dietary recommendations for the prevention of depression, Nutr Neurosci source

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    • cites [201] Psaltopoulou, 2013, Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis, Ann Neurol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    From the existing literature, a clear interaction between diet and the microbiota-brain communication across the lifespan emerges.

    “From the existing literature, a clear interaction between diet and the microbiota-brain communication across the lifespan emerges.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    SCFAs can stimulate neurotrophic factors or neurotransmitter synthesis, thereby regulating growth, survival, differentiation, and excitability of neurons and synapses in the CNS and playing an important part in learning, memory, stress, and mood.

    “Additionally, SCFAs can stimulate neurotrophic factors [nerve growth factor, BDNF, and glial cell line-derived neurotrophic factor (352)] or neurotransmitter synthesis [glutamate, glutamine, and GABA (353)], thus regulating the growth, survival, differentiation, and excitability of neurons and synapses in the CNS (352) and playing an important part in learning, memory, stress, and mood.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [352] Moris, 2003, Neurotrophic factors: basis for their clinical application, Neurologia

      Not checked in the free run.

    • cites [353] Frost, 2014, The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The microbiota composition was rescued prior to cognitive changes and the positive effects of beta-glucan were eliminated with antibiotic treatment, suggesting a potential causal relation between diet-induced microbial alterations and cognitive function.

    “Importantly, the microbiota composition was rescued prior to cognitive changes and the positive effects of β-glucan were eliminated with antibiotic treatment (321), suggesting a potential causal relation between diet-induced microbial alterations and cognitive function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [321] Shi, 2020, β-Glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice, Microbiome source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the NU-AGE cohort, Mediterranean diet-induced increases in microbial taxa were associated with improved cognition and reduced risk of frailty and inflammation in elderly individuals who followed a customized Mediterranean diet for 12 months.

    “In the NU-AGE cohort, Mediterranean diet-induced increases in microbial taxa were associated with improved cognition and reduced risk of frailty and inflammation in elderly individuals who followed a customized Mediterranean diet for 12 mo (300).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [300] Ghosh, 2020, Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among interventional studies using whole-dietary approaches published to date, only one included healthy adults as volunteers, and reported improved nutritional behaviors and intrapersonal emotional competence following a diet rich in inulin-type fructans.

    “Among the interventional studies using whole-dietary approaches published to date, only one included healthy adults as volunteers, and reported improved nutritional behaviors and intrapersonal emotional competence following a diet rich in inulin-type fructans (331).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [331] Hiel, 2019, Effects of a diet based on inulin-rich vegetables on gut health and nutritional behavior in healthy humans, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While there is existing evidence from clinical interventions showing improvements in depression and anxiety symptoms following dietary manipulation, these studies have not, to date, collected gut microbiota data.

    “While there is existing evidence from clinical interventions showing improvements in depression and anxiety symptoms following dietary manipulation (199, 311, 326), these studies have not, to date, collected gut microbiota data.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [199] Jacka, 2017, A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial), BMC Med source

      Not checked in the free run.

    • cites [311] Parletta, 2019, A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: a randomized controlled trial (HELFIMED), Nutr Neurosci source

      Not checked in the free run.

    • cites [326] Francis, 2019, A brief diet intervention can reduce symptoms of depression in young adults—a randomised controlled trial, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Even short-term diet exposure (2 weeks) shifted the microbiota composition in a way that was associated with inflammation-related pathways and memory deficits, indicating rapid effects on microbiota and brain function.

    “Likewise, even short-term diet exposure (2 wk) shifted the microbiota composition in a way that was associated with inflammationrelated pathways and memory deficits (325), indicating rapid effects on microbiota and brain function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [325] Beilharz, 2016, The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity, Brain Behav Immun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In juvenile rats, positive correlations between a diet-linked increase in Lactobacillus and mRNA expression of neuronal activation and serotonin receptors were described, suggesting that effects of diet on brain chemistry are mediated by certain microbes.

    “In juvenile rats, positive correlations between a diet-linked increase in Lactobacillus and mRNA expression of neuronal activation and serotonin (5-HT) receptors were described (316), suggesting that effects of diet on brain chemistry are mediated by certain microbes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [316] Mika, 2018, Feeding the developing brain: juvenile rats fed diet rich in prebiotics and bioactive milk fractions exhibit reduced anxiety-related behavior and modified gene expression in emotion circuits, Neurosci Lett source

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  • May combine two claims.

    Premisecitation

    In a pilot study with 47 healthy young medical students, consumption of a fermented milk drink containing L. casei strain Shirota was able to reduce physical symptoms of stress such as abdominal pain or cold symptoms, prevented the increase in salivary cortisol observed in the placebo group, and could potentially normalize stress-induced aberration in tryptophan metabolism and improve 5-HT

    “In a pilot study with 47 healthy young medical students, consumption of a fermented milk drink containing L. casei strain Shirota was able to reduce physical symptoms of stress such as abdominal pain or cold symptoms, prevented the increase in salivary cortisol observed in the placebo group, and could potentially normalize stress-induced aberration in tryptophan metabolism and improve 5-HT”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [344] Kato-Kataoka, 2016, Fermented milk containing Lactobacillus casei strain Shirota prevents the onset of physical symptoms in medical students under academic examination stress, Benef Microbes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    B. longum 1417 modulated resting neural activity as well as neural responses to social stress, while supplementation with beta-galactooligosaccharide reduced the salivary cortisol awakening response and improved emotional information processing, and an oligofructose-enriched inulin improved memory and mood in healthy volunteers.

    “For example, B. longum 1417 modulated resting neural activity as well as neural responses to social stress, while supplementation with β-galactooligosaccharide reduced the salivary cortisol awakening response, a biochemical measure of stress, and improved emotional information processing (329), and an oligofructose-enriched inulin improved memory and mood in healthy volunteers (330).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [329] Schmidt, 2015, Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers, Psychopharmacology (Berl) source

      Not checked in the free run.

    • cites [330] Smith, 2015, An investigation of the acute effects of oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performance, Nutrients source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prior treatment with a probiotic (VSL#3, containing 3 strains of bifidobacteria, 4 strains of lactobacilli, and 1 strain of Streptococcus) was able to prevent diet-induced cognitive deficits in the hippocampal-dependent place recognition task and rescue specific bacterial taxa that were decreased by exposure to a cafeteria diet.

    “Interestingly, prior treatment with a probiotic (VSL#3, containing 3 strains of bifidobacteria, 4 strains of lactobacilli, and 1 strain of Streptococcus) was able to prevent dietinduced cognitive deficits in the hippocampal-dependent place recognition task and rescue specific bacterial taxa that were decreased by exposure to a cafeteria diet (317).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [317] Beilharz, 2018, Cafeteria diet and probiotic therapy: cross talk among memory, neuroplasticity, serotonin receptors and gut microbiota in the rat, Mol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Strong associations between increased behavioral reactivity and a microbial profile elicited by a high-starch diet, as well as more settled behaviors associated with microbes promoted by a high-fiber diet, were observed in horses.

    “Likewise, strong associations between increased behavioral reactivity and a microbial profile elicited by a high-starch diet, as well as more settled behaviors associated with microbes promoted by a highfiber diet, were observed in horses (323).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [323] Bulmer, 2019, High-starch diets alter equine faecal microbiota and increase behavioural reactivity, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SCFAs, specifically butyrate, enhance blood-brain barrier integrity by increasing occludin expression, thereby protecting the brain from potential neurotoxic factors.

    “In addition, SCFAs, specifically butyrate, were also shown to enhance BBB integrity by increasing occludin expression (355, 356), thereby protecting the brain from potential neurotoxic factors.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [355] Li, 2016, Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice, Brain Res source

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    • cites [356] Sun, 2016, Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress, Neurosci Lett source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Administration of microbial metabolites that were differentially increased after intermittent fasting resulted in improved cognitive function in animals, partially supporting a causal role for microbial metabolites in improving cognition.

    “Recently, the administration of microbial metabolites that were found to be differentially increased after intermittent fasting resulted in improved cognitive function, partially supporting a causal role for microbial metabolites in improving cognition in animals (320).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [320] Liu, 2020, Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an animal model, administration of SCFAs reduced depressive-like behavior, stress responsiveness, and intestinal permeability associated with psychosocial stress.

    “In an animal model, administration of SCFAs reduced behavioral deficits (depressive-like behavior), stress responsiveness and intestinal permeability associated with psychosocial stress (354)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [354] van de Wouw, 2018, Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations, J Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In another recent animal study, supplementation with the prebiotic beta-glucan abrogated microbiota alterations and cognitive impairment as well as microglia activation and neuroinflammation induced by a high-fat, fiber-deficient diet.

    “In another recent animal study, supplementation with the prebiotic β-glucan abrogated microbiota alterations and cognitive impairment as well as microglia activation and neuroinflammation induced by a high-fat, fiber-deficient diet (321).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [321] Shi, 2020, β-Glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice, Microbiome source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an obese population, a nutrition education program focusing on the gut microbiota resulted in a decrease in the depression score and an increase in self-rated health, as well as an increase in alpha-diversity and abundance of beneficial bacteria such as B. bifidum and S. thermophilus.

    “In an obese population, a nutrition education program focusing on the gut microbiota (increase in fiber-containing and fermented foods) resulted in a decrease in the depression score and an increase in selfrated health, as well as an increase in α-diversity and abundance of beneficial bacteria such as B. bifidum and S. thermophilus (332).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [332] Uemura, 2019, Obesity and mental health improvement following nutritional education focusing on gut microbiota composition in Japanese women: a randomised controlled trial, Eur J Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Kynurenine can cross the blood-brain barrier and be further metabolized to neuroactive glutamatergic products, such as kynurenic and quinolinic acid.

    “Kynurenine can cross the BBB and be further metabolized to neuroactive glutamatergic products, such as kynurenic and quinolinic acid.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A direct effect of intestinally produced 5-HT on the brain is unlikely because it cannot penetrate the blood-brain barrier; stimulation of vagal afferents and regulation of immune responses could be potential signaling pathways.

    “While a direct effect of intestinally produced 5-HT on the brain is unlikely as it cannot penetrate the BBB, stimulation of vagal afferents and regulation of the immune responses could be potential signaling pathways (388, 389).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [388] Mawe, 2013, Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets, Nat Rev Gastroenterol Hepatol source

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    • cites [389] Shajib, 2017, Diverse effects of gut-derived serotonin in intestinal inflammation, ACS Chem Neurosci source

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  • May combine two claims.

    Premisecitation

    Production of 5-HT can affect peripheral tryptophan availability and thus indirectly affect brain 5-HT levels, suggesting that peripheral alterations in 5-HT can affect the central 5-HT signaling system.

    “Additionally, the production of 5-HT can affect peripheral tryptophan availability and, thus, indirectly affect brain 5-HT levels, suggesting that peripheral alterations in 5-HT can affect the central 5-HT signaling system (390, 391).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [390] Muller, 2016, The serotonin system in autism spectrum disorder: from biomarker to animal models, Neuroscience source

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    • cites [391] Elliott, 2019, Role of tryptophan in microbiota-induced depressive-like behavior: evidence from tryptophan depletion study, Front Behav Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BCFAs could be especially important microbial messengers in scenarios of high-protein, low-complex carbohydrate consumption, as studies have shown that consumption of these diets can increase microbial production of BCFAs.

    “BCFAs could be especially important microbial messengers in scenarios of high-protein, low-complex carbohydrate (i.e., dietary fiber) consumption, as studies have shown that consumption of these diets can increase the microbial production of BCFAs (121, 380, 381).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [121] Russell, 2011, High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health, Am J Clin Nutr source

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    • cites [380] Aguirre, 2016, Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model, Res Microbiol source

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    • cites [381] Hald, 2016, Effects of arabinoxylan and resistant starch on intestinal microbiota and short-chain fatty acids in subjects with metabolic syndrome: a randomised crossover study, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SCFAs activate vagal afferents in the gastrointestinal tract, transducing electric signals to modulate neurotransmitter levels in the brain and brain function.

    “SCFAs also activate vagal afferents in the gastrointestinal tract (364), transducing electric signals to modulate neurotransmitter levels in the brain and brain function.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [364] Lal, 2001, Vagal afferent responses to fatty acids of different chain length in the rat, Am J Physiol Gastrointest Liver Physiol source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    These tryptophan metabolites serve as important bioactive messengers in microbiota-brain communication and can be modulated by dietary intake, specifically protein.

    “These metabolites serve as important bioactive messengers in the microbiota-brain communication and can be modulated by dietary intake, specifically protein.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Kynurenic acid is usually neuroprotective as an NMDA receptor antagonist, whereas quinolinic acid acts as an NMDA receptor agonist and exerts neurotoxic effects.

    “As an antagonist to the N-methyl-d-aspartate (NMDA) receptor, kynurenic acid is usually neuroprotective, whereas quinolinic acid acts as an agonist to the NMDA receptor and exerts neurotoxic effects (393).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [393] Stone, 2001, Kynurenic acid antagonists and kynurenine pathway inhibitors, Expert Opin Investig Drugs source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effect of SCFAs on inflammation can be mediated by improvement of the intestinal barrier, potentially preventing immune molecules and bacterial LPS from translocating into the periphery and thus reducing systemic inflammation and ultimately neuroinflammation.

    “The effect of SCFAs on inflammation can be mediated by improvement of the intestinal barrier (361), thereby potentially preventing immune molecules and bacterial LPS translocating into the periphery and thus reducing systemic inflammation and ultimately neuroinflammation (362).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [361] Bach Knudsen, 2018, Impact of diet-modulated butyrate production on intestinal barrier function and inflammation, Nutrients source

      Not checked in the free run.

    • cites [362] Leigh, 2020, Diet, inflammation and the gut microbiome: mechanisms for obesity-associated cognitive impairment, Biochim Biophys Acta Mol Basis Dis source

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  • May combine two claims.

    Premisecitation

    Microbial proteolytic activity influences the availability of amino acids to the host and results in the production of bioactive metabolites including neurotransmitters, BCFAs, amines, phenols, and indoles.

    “Microbial proteolytic activity not only influences the availability of amino acids to the host (375), but also results in the production of bioactive metabolites [e.g., neurotransmitters, BCFAs, amines, phenols, and indoles (376)].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [375] Metges, 2000, Contribution of microbial amino acids to amino acid homeostasis of the host, J Nutr source

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    • cites [376] Macfarlane, 1992, Estimation of short-chain fatty acid production from protein by human intestinal bacteria based on branched-chain fatty acid measurements, FEMS Microbiol Ecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HDACs have been implicated in a range of neuropsychiatric disorders, including depression and schizophrenia, and HDAC inhibitors could be potential cognitive enhancers in anxiety- and fear-related disorders.

    “HDACs have been implicated in a range of neuropsychiatric disorders [e.g., depression and schizophrenia (358)] and HDAC inhibitors could be potential cognitive enhancers in anxiety-and fear-related disorders (359).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [358] Volmar, 2015, Histone deacetylases (HDACs) and brain function, Neuroepigenetics source

      Not checked in the free run.

    • cites [359] Whittle, 2014, HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?, Biochem Soc Trans source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Trimethylamine (TMA) is produced by microbial metabolism from dietary choline, and once absorbed, TMA is converted to TMAO, which has been implicated in various chronic diseases, especially those related to the circulatory system.

    “Lastly, a large research focus has also been placed on the microbial production of trimethylamine (TMA) from dietary choline.Once absorbed, TMA is converted to TMAO, which has been implicated in various chronic diseases, especially those related to the circulatory system [e.g., stroke (386)].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [386] Farhangi, 2020, Gut microbiota-associated metabolite trimethylamine N-oxide and the risk of stroke: a systematic review and dose-response meta-analysis, Nutr J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microbially derived secondary bile acids are hypothesized to be interkingdom signaling molecules due to their ability to influence the composition and function of the gut microbiota as well as host physiology.

    “Microbially derived secondary bile acids are hypothesized to be interkingdom signaling molecules due to their ability to influence the composition and function of the gut microbiota as well as host physiology (407, 408).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [407] Ridlon, 2015, The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics, Acta Pharm Sin B source

      Not checked in the free run.

    • cites [408] Joyce, 2016, Bile acid modifications at the microbe-host interface: potential for nutraceutical and pharmaceutical interventions in host health, Annu Rev Food Sci Technol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bioavailability and some biological activity of ω-3 fatty acids or polyphenols might be dependent on conversion by the gut microbiota.

    “However, bioavailability and some biological activity might also be dependent on conversion by the gut microbiota (413), which is the case in the interaction between polyphenols, microbiota, and associated beneficial effects (507).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [413] Pasinetti, 2018, The role of the gut microbiota in the metabolism of polyphenols as characterized by gnotobiotic mice, J Alzheimers Dis source

      Not checked in the free run.

    • cites [507] Espin, 2017, The gut microbiota: a key factor in the therapeutic effects of (poly)phenols, Biochem Pharmacol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some reports suggest bile acids can cross the blood-brain barrier, whereas other bile acid conjugates signal directly to the brain as neuroactive ligands by binding FXR and TGR5 in the CNS or indirectly by binding these receptors in the gastrointestinal tract and initiating a signaling cascade.

    “Some reports suggest that bile acids can cross the BBB, whereas other bile acid conjugates have been shown to signal directly to the brain as neuroactive ligands, either by binding to farnesoid X receptor and Takeda G protein-coupled receptor 5 (TGR5) present in the CNS or indirectly by binding these receptors in the gastrointestinal tract and initiating a signaling cascade (411).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [411] Mertens, 2017, Bile acid signaling pathways from the enterohepatic circulation to the central nervous system, Front Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats, bile acids increase permeability of the blood-brain barrier, which could increase the flow of other neuroactive metabolites or neurotoxins into the brain and affect brain function and behavior.

    “In rats, bile acids were also demonstrated to increase permeability of the BBB (412), which could increase the flow of other neuroactive metabolites or neurotoxins into the brain and affect brain function and behavior.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [412] Quinn, 2014, Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms, Dig Liver Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ferulic acid is broken down by esterase activity of Lactobacillus spp. into 4-vinylguaiacol and hydroferulic acid and further converted into caffeic and vanillic acids.

    “For example, ferulic acid, a phenolic compound found in plant stems and various herbs, is broken down by the esterase activity of Lactobacillus spp.into 4-vinylguaiacol and hydroferulic acid (414) and further converted into caffeic and vanillic acids.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [414] Knockaert, 2012, Carrot β-carotene degradation and isomerization kinetics during thermal processing in the presence of oil, J Agric Food Chem source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An increase in indole-3-lactic acid and indole-3-propionic acid was observed after the Mediterranean diet, but these metabolites were decreased after the fast-food diet.

    “An increase in indole-3-lactic acid and indole-3-propionic acid, which have been shown to confer beneficial effects on neuronal cells, was observed after the Mediterranean diet, but these metabolites were decreased after the fast-food diet.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Indoles increase the expression of inflammation-associated genes by binding to certain receptors and can bind to 5-HT receptors to impact behavior and gut motility.

    “Additionally, indoles increase the expression of inflammation-associated genes by binding to certain receptors (e.g., aryl hydrocarbon receptor) and can bind to 5-HT receptors to impact behavior and gut motility (405).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [405] Tomberlin, 2017, Indole: an evolutionarily conserved influencer of behavior across kingdoms, Bioessays source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    An individual response to fiber could depend on initial target bacterial levels, and individuals with the lowest fiber intakes and limited microbial richness at baseline might have the most to gain from increasing fiber intake and exhibit greater microbiota changes.

    “Thus, an individual response to fiber could depend on the initial target bacterial levels and those individuals with the lowest fiber intakes and a limited microbial richness at baseline potentially might have the most to gain from increasing fiber intake and exhibit greater microbiota changes (505).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [505] Jefferson, 2019, The effects of intact cereal grain fibers, including wheat bran on the gut microbiota composition of healthy adults: a systematic review, Front Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Abnormal bile acid metabolism has been described in neurological diseases, suggesting a role for transformation of bile acids by gut microbiota in Alzheimer's disease development/progression and cognitive decline.

    “Recently, abnormal bile acid metabolism was described in neurological diseases, suggesting a role for the transformation of bile acids by gut microbiota as a factor in Alzheimer's disease development/progression and cognitive decline (409, 410).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [409] MahmoudianDehkordi, 2019, Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease—an emerging role for gut microbiome, Alzheimers Dement source

      Not checked in the free run.

    • cites [410] Bhargava, 2014, Gut microbiome and multiple sclerosis, Curr Neurol Neurosci Rep source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    A relatively stable microbiota might benefit from a stable diet, whereas an unstable microbiota could mean a flexible response to dietary intervention and constant re-evaluation of the optimal diet.

    “Thus, a relatively stable microbiota might benefit from a stable diet, whereas an unstable microbiota could mean a flexible response to dietary intervention and constant re-evaluation of the optimal diet (506).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [506] Hughes, 2019, The role of the gut microbiome in predicting response to diet and the development of precision nutrition models. Part II: results, Adv Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a human intervention study, nonresponders showed increased negative interactions between microbial species after intervention, while responders showed increased positive interactions and complexity of interactions.

    “In a human intervention study, network complexity analysis revealed that in nonresponders the negative interactions between microbial species increased after the intervention, meaning that more species competed for the same substrate, whereas in responders the positive interactions between species and the complexity of interactions increased after the intervention (70).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] Kovatcheva-Datchary, 2015, Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella, Cell Metab source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Manipulating the microbiota through diet might be more feasible in the longer term and an economically cheaper solution than probiotic supplementation.

    “Moreover, although there is some evidence for the use of probiotics as supplements, manipulating the microbiota through diet might be more feasible in the longer term and an economically cheaper solution than probiotic supplementation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    GF status or antibiotic treatment abolished the antiseizure effect of the ketogenic diet, and fecal transplant of a microbiota induced by the ketogenic diet elicited seizure protection.

    “The authors not only showed that GF status or antibiotic treatment abolished the antiseizure effect of the ketogenic diet, but fecal transplant of a microbiota induced by the ketogenic diet also elicited seizure protection.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [341] Olson, 2018, The gut microbiota mediates the anti-seizure effects of the ketogenic diet, Cell source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The existing data consistently support increasing the intake and variety of plant foods and reducing or eliminating ultraprocessed foods.

    “While the evidence from intervention studies in humans is limited, the existing data consistently support increasing the intake and variety of plant foods and reducing or eliminating ultraprocessed foods.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The missing microbes do not necessarily have to be supplied by probiotic supplements, but could be consumed through food products containing beneficial bacteria, such as fermented foods.

    “Thereby, the missing microbes do not necessarily have to be supplied by probiotic supplements, but could be consumed through food products containing beneficial bacteria, such as fermented foods.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Animal diet formulations used in dietary studies often provide doses that are outside of the daily intake in human populations.

    “Likewise, dietary studies in animal models may not always be translatable to human populations as animal diet formulations used in the studies often provide doses that are outside of the daily intake in human populations, so that the translational capacity of these studies should be considered.”
    Quote in the paperNot a substantial claim
123 of 123

  • The paper relies on this without support.

    Findings from animal models of diet-microbiota-gut-brain interactions are informative about human biology.

    “Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication.”

  • The paper relies on this without support.

    Chemical properties of different fibers determine the location of metabolism within the gastrointestinal tract, leading to specific microbial changes in response to their ingestion.

    “More specifically, the chemical properties (e.g., polymerization, solubility, and viscosity) of different fibers determine the location of metabolism within the gastrointestinal tract, leading to specific microbial changes in response to their ingestion.”

  • The paper relies on this without support.

    Adequate maternal nutrition is key to the development of the growing fetus and nutrient inadequacies are established causes for neurological abnormalities.

    “Adequate maternal nutrition is key to the development of the growing fetus and nutrient inadequacies are established causes for neurological abnormalities (e.g., low folate intake and neural tube defect).”

  • The paper relies on this without support.

    Microbiota underdevelopment due to inadequate nutrition can have overarching consequences.

    “Microbiota underdevelopment due to inadequate nutrition can have overarching consequences.”

  • The paper relies on this without support.

    There is a lack of research studies investigating factors that predict the effect of diet interventions on cognitive outcomes.

    “While advances in predicting an individual's response to a diet intervention have been made, there is a lack of research studies investigating factors that predict the effect on cognitive outcomes.”

  • The paper relies on this without support.

    There is no clear consensus yet as to how dietary patterns direct host responses.

    “Extensive characterization of baseline dietary habits will also be crucial, as there is no clear consensus yet as to how dietary patterns direct host responses.”

  • The paper relies on this without support.

    Dietary fiber is fermented by the gut microbiota, supporting the growth and activity of SCFA-producing bacteria and increasing the production of SCFAs.

    “Inaccessible to the host, dietary fiber is fermented by the gut microbiota, supporting the growth and activity of SCFAproducing bacteria and increasing the production of SCFAs.”

  • The paper relies on this without support.

    SCFAs can directly or indirectly signal to the brain, influencing brain physiology and behavior.

    “In turn, SCFAs can directly or indirectly signal to the brain, influencing brain physiology and behavior.”

  • The paper relies on this without support.

    ω-3 fatty acids or polyphenols are potent modulators of brain physiology and can be neuroprotective.

    “On its own, these nutrients are potent modulators of brain physiology and can be neuroprotective.”

  • The paper relies on this without support.

    Microbial extinction is partly attributed to unhealthy eating patterns, such as increased consumption of processed and fried food and low fiber intake.

    “Given the increasing knowledge that microbial extinction is partly attributed to unhealthy eating patterns, such as increased consumption of processed and fried food and low fiber intake, it may be that future nutritional interventions will combine dietary approaches with specifically designed probiotics in order for the dietary intervention to be effective.”

  • The paper relies on this without support.

    There has been little human research investigating the diet-microbiota-brain interaction thus far.

    “While preclinical studies have begun to elucidate the diet-microbiota-brain interaction, there has been little human research investigating this intricate relation thus far.”
11 of 11

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Dietary factors that increase the relative abundance of anti-inflammatory and other health-promoting bacteria include prebiotics such as oligosaccharides and polyphenols, some of which have prebiotic-like effects.

    “Dietary factors that increase the relative abundance of these anti-inflammatory and other health-promoting bacteria include prebiotics such as oligosaccharides and polyphenols some of which have prebiotic-like effects [42].”

    From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [42]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure reverses which factor is the moderator

    Minor

    The text describes the microbiota as strengthening the diet-host relation, whereas Figure 3 describes diet as strengthening or weakening the microbiota-brain relation.

  • Claim of improved Alzheimer's biomarkers conflicts with table

    Minor

    The narrative says microbial changes correlated with improved cerebrospinal-fluid biomarkers after the diet, but Table 2 says postintervention changes in those biomarkers were not reported.

2 of 2

Cites

1 retracted

Flagged first, then by citations

1 of the 531 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Salonen, 2014, Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men, ISME J, 8, 2218, 10.1038/ismej.2014.63 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F.
Affiliations
  • APC Microbiome Institute (IE)
  • Barwon Health (AU)
  • Teagasc - The Irish Agriculture and Food Development Authority (IE)
  • University College Cork (IE)
Corresponding author
Cryan, John F
ORCID
Venue
Advances in Nutrition
Publisher
Elsevier BV
Published
2021-07
Volume
12
Issue
4
Pages
1239-1285
ISSN
  • 2156-5376 (ISSN-L)
  • 2161-8313
DOI
10.1093/advances/nmaa181
PMC
PMC8321864
OpenAlex
W3135540293
Semantic Scholar
db109b4969b0b2de7340698f449b604779d91d52
Cited by
451
References
531
Citations by year
2026: 130 · 2025: 120 · 2024: 87 · 2023: 67 · 2022: 38 · 2021: 9
FWCI
2.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Advances in Nutrition (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ResearchOnline - JCU (James Cook University) (submittedVersion)
  • Deakin Research Online (Deakin University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • T-Stór (Teagasc) (submittedVersion, cc-by-nc-sa)
Funders
  • APC Microbiome Ireland
  • Science Foundation Ireland (12/RC/2273 P2)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, microbiota-gut-brain axis, diet, mental health, microbial metabolites, immune pathways, neural pathways, metabolic pathways, dietary intervention, brain health
MeSH terms
Gastrointestinal Microbiome, Animals, Brain, Diet, Humans, Mental Health, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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