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Cited by 32Gastrointestinal motility and disordersGut microbiota and healthProbiotics and Fermented Foods

Chronic constipation and gut microbiota: current research insights and therapeutic implications

Open access
Xu, Xiaoqian, Wang, Yali, Long, Yiyan, Cheng, Yanli·2024·Postgraduate Medical Journal
DOI 10.1093/postmj/qgae112
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Abstract

Chronic constipation is a prevalent clinical condition. Its etiology and pathogenesis have not yet been fully understood. In recent years, mounting evidence suggests a close association between chronic constipation and intestinal dysbiosis, including alterations in the colony structure and metabolites, as well as the modulation of bowel movements via the brain–gut–microbiota axis. With the deepening of related research, probiotic-related therapies are expected to become a potential first-line treatment for chronic constipation in the future. In this review, we summarize the current research insights into the intricate relationships between chronic constipation and the gut microbiota and briefly discuss several different approaches for treating chronic constipation. The findings from this review may advance our understanding of the pathological mechanisms underlying chronic constipation and, ultimately, translate them into improvements in patient care.

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  • Premisecitation

    There is no significant difference in the overall diversity of microbiota in chronic constipation.

    “Nevertheless, there is no significant difference in the overall diversity of microbiota [14,16].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Sekirov, 2010, Gut microbiota in health and disease, Physiol Rev source

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    • cites [16] Huang, 2018, Analysis of fecal microbiota in patients with functional constipation undergoing treatment with synbiotics, Eur J Clin Microbiol Infect Dis source

      Not checked in the free run.

  • Premisecitation

    The gut microbiota can regulate the expression of genes involved in intestinal peristalsis.

    “One explanation suggests that the gut microbiota can regulate the expression of genes involved in intestinal peristalsis.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Sekirov, 2010, Gut microbiota in health and disease, Physiol Rev source

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    • cites [17] Parthasarathy, 2016, Relationship between microbiota of the colonic mucosa vs Feces and symptoms, colonic transit, and methane production in female patients with chronic constipation, Gastroenterology source

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  • Premisecitation

    Weakened anti-reflux effect of the ileocecal valve caused by weakened intestinal motility can lead to translocation of bacteria from the colon to the small intestine.

    “Simultaneously, the weakened anti-ref lux effect of the ileocecal valve, caused by weakened intestinal motility, can also lead to the translocation of bacteria from the colon to the small intestine.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Yang, 2022, Gut microbiota: a new avenue to reveal pathological mechanisms of constipation, Appl Microbiol Biotechnol source

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  • Premisecitation

    Patients with IBS with constipation exhibit a higher proportion of Clostridium, Escherichia coli, Salmonella, Shigella, and Pseudomonas in the gut microbiota.

    “Patients with IBS with constipation also exhibit a higher proportion of Clostridium, Escherichia coli, Salmonella, Shigella, and Pseudomonas in the gut microbiota [13].”
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    • cites [13] Distrutti, 2016, Gut microbiota role in irritable bowel syndrome: new therapeutic strategies, World J Gastroenterol source

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  • Premisecitation

    Across different types of constipation, there is consistency in findings of decreased relative abundance of beneficial bacteria such as lactic acid- and butyric acid-producing bacteria, and increased abundance of methanogenic bacteria and conditionally pathogenic bacteria.

    “Although the intestinal environment and gut microbiota composition may vary among different types of constipation, there is consistency in findings of a decrease in the relative abundance of beneficial bacteria, such as lactic acid-and butyric acid-producing bacteria, as well as an increase in the abundance of methanogenic bacteria and conditionally pathogenic bacteria [14,15].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Sekirov, 2010, Gut microbiota in health and disease, Physiol Rev source

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    • cites [15] Martin, 2018, The brain-gut-microbiome axis, Cell Mol Gastroenterol Hepatol source

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    Premisecitation

    Metabolites of various gut microbiota, especially bacteria attached to the intestinal mucosa, cause intestinal smooth muscle contraction.

    “The other explanation is that the ref lexivity of metabolites of various gut microbiota (especially the bacteria attached to the intestinal mucosa) causes intestinal smooth muscle contraction [14,17].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Sekirov, 2010, Gut microbiota in health and disease, Physiol Rev source

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    • cites [17] Parthasarathy, 2016, Relationship between microbiota of the colonic mucosa vs Feces and symptoms, colonic transit, and methane production in female patients with chronic constipation, Gastroenterology source

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    Premisecitation

    In patients with chronic constipation, there is evidence of intestinal dysbacteriosis characterized by decreased abundance of Bifidobacterium spp., Lactobacillus spp., Prevotella spp., and butyrate-producing genera, and increased abundance of Coprococcus, Ruminococcus spp., Akkermansia, and Clostridium spp.

    “In patients with chronic constipation, there is evidence of intestinal dysbacteriosis, characterized by a decrease in the abundance of Bifidobacterium spp., Lactobacillus spp., Prevotella spp., and butyrate-producing genera [10], but an increase in the abundance of Coprococcus, Ruminococcus spp., Akkermansia, and Clostridium spp.[11,12].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [10] Tian, 2020, Potential role of fecal microbiota in patients with constipation, Ther Adv Gastroenterol source

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    • cites [11] Zhang, 2021, Fecal microbiota transplantation modulates the gut Flora Favoring patients with functional constipation, Front Microbiol source

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    • cites [12] Li, 2023, The gut microbiome and metabolites are altered and interrelated in patients with functional constipation, Front Microbiol source

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    Premisecitation

    In chronic constipation, weakened intestinal motility and prolonged intestinal movement time contribute to overgrowth of small intestinal bacteria and promotion of colonization of slow-growing microorganisms in the intestine.

    “In chronic constipation, weakened intestinal motility and a prolonged intestinal movement time contribute to the overgrowth of small intestinal bacteria as well as promotion of the colonization of slow-growing microorganisms in the intestine.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Yang, 2022, Gut microbiota: a new avenue to reveal pathological mechanisms of constipation, Appl Microbiol Biotechnol source

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    Premisecitation

    Disruption of microbiota balance can lead to a reduction in some metabolites and slowed intestinal peristalsis, resulting in accumulation of indigestible oligosaccharides in the large intestine, which causes abdominal pain, bloating, and constipation.

    “Disruption of the microbiota balance can lead to a reduction in some metabolites and slowed intestinal peristalsis, resulting in the accumulation of indigestible oligosaccharides in the large intestine, which in turn causes symptoms, such as abdominal pain, bloating, and constipation [2].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Takeoka, 2023, Prevalence of irritable bowel syndrome in Japan, China, and South Korea: an international cross-sectional study, J Neurogastroenterol Motil source

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    Premisecitation

    When SCFA concentration surpasses a certain threshold, SCFAs stimulate electrolyte absorption, inhibit mucin secretion, and lead to the occurrence and development of constipation.

    “When the concentration of SCFAs surpasses a certain threshold, they can stimulate electrolyte absorption, inhibit the secretion of mucin, and lead to the occurrence and development of constipation;”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [17] Parthasarathy, 2016, Relationship between microbiota of the colonic mucosa vs Feces and symptoms, colonic transit, and methane production in female patients with chronic constipation, Gastroenterology source

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    • cites [33] Makizaki, 2021, Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis, PLoS One source

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    • cites [34] Yarullina, 2020, Characterization of gut contractility and microbiota in patients with severe chronic constipation, PLoS One source

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    Premisecitation

    In chronic constipation, physiological bacteria in the small intestine are replaced by pathogenic bacteria from the colon, resulting in major changes in the structure and function of the overall gut microbiota, which contribute to development or aggravation of constipation symptoms.

    “Consequently, the physiological bacteria in the small intestine are replaced by pathogenic bacteria from the colon, resulting in major changes in the structure and function of the overall gut microbiota [18], which in turn contribute to the development or aggravation of constipation symptoms.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Yang, 2022, Gut microbiota: a new avenue to reveal pathological mechanisms of constipation, Appl Microbiol Biotechnol source

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    Premisecitation

    Chronic constipation is often accompanied by damage to the intestinal barrier and low-grade inflammation.

    “Chronic constipation is often accompanied by damage to the intestinal barrier and low-grade inf lammation [19,20].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Debnath, 2021, Gut-microbiota derived bioactive metabolites and their functions in host physiology, Biotechnol Genet Eng Rev source

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    • cites [20] Iancu, 2023, Revisiting the intestinal microbiome and its role in Diarrhea and constipation, Microorganisms source

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    Premisecitation

    There is a bidirectional relationship between the gut microbiota and BAs, in which the gut microbiota regulates the metabolism and synthesis of BAs, while the composition of BAs affects the diversity and homeostasis of the gut microbiota.

    “There is a bidirectional relationship between the gut microbiota and BAs, in which the gut microbiota regulates the metabolism and synthesis of BAs, while the composition of BAs also affects the diversity and homeostasis of the gut microbiota [35].”
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    • cites [35] Guo, 2022, Interactive relationships between intestinal flora and bile acids, Int J Mol Sci source

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    Premisecitation

    Methane activates voltage-dependent potassium channels in colonic smooth muscle cells, resulting in hyperpolarization of the cell membrane, reducing extracellular calcium influx and inhibiting contraction of the proximal colonic longitudinal muscle, ultimately causing constipation.

    “Methane activates voltage-dependent potassium channels in colonic smooth muscle cells, resulting in hyperpolarization of the cell membrane.This, in turn, reduces extracellular calcium inf lux and inhibits the contraction of the proximal colonic longitudinal muscle, ultimately causing constipation [20,40,41].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [20] Iancu, 2023, Revisiting the intestinal microbiome and its role in Diarrhea and constipation, Microorganisms source

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    • cites [40] Roccarina, 2010, The role of methane in intestinal diseases, Am J Gastroenterol source

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    • cites [41] Park, 2017, The effects and mechanism of action of methane on ileal motor function, Neurogastroenterol Motil source

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    Premisecitation

    Hydrogen produced by Acetivibrio increases intestinal peristalsis, and the abundance of Acetivibrio decreases during constipation, resulting in weakened intestinal peristalsis.

    “In addition, hydrogen produced by Acetivibrio increases intestinal peristalsis, and the abundance of Acetivibrio decreases during constipation, resulting in weakened intestinal peristalsis [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Makizaki, 2021, Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis, PLoS One source

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    Premisecitation

    SCFAs can reduce the pH value in the intestinal lumen, reduce inflammation, and promote colonic movement.

    “For instance, SCFAs can reduce the pH value in the intestinal lumen, reduce inf lammation, and promote colonic movement [6,28];”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Lai, 2023, Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial, Gut Microbes source

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    • cites [28] Zhang, 2021, Role of gut microbiota in functional constipation, Gastroenterol Rep source

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    Premisecitation

    A small amount of SCFAs can regulate the expression of enzymes responsible for 5-HT production and reuptake transporters in intestinal epithelial cells, promoting 5-HT production, which enhances intestinal peristalsis and relieves constipation.

    “However, studies have found that a small amount of SCFAs can regulate the expression of enzymes responsible for 5-HT production and reuptake transporters in intestinal epithelial cells.This regulation promotes 5-HT production, which in turn enhances intestinal peristalsis, thus providing relief from constipation [30,31].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [30] Liu, 2022, Interaction between the gut microbiota and intestinal motility, Evid Based Complement Alternat Med source

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    • cites [31] Huang, 2018, Microbial treatment in chronic constipation, Sci China Life Sci source

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    Premisecitation

    Secondary BAs in the intestine stimulate intestinal motility and regulate the structure of the gut microbiota.

    “Secondary BAs in the intestine not only stimulate intestinal motility, but also regulate the structure of the gut microbiota [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Wang, 2020, Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation, BMC Gastroenterol source

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    Premisecitation

    A balanced gut microbiota maintains the stability of the intestinal epithelial barrier and preserves the integrity of the physical intestinal barrier by regulating expression of tight junction proteins, creating an acidic environment in the intestinal lumen, and producing mucin-related peptides.

    “A balanced gut microbiota maintains the stability of the intestinal epithelial barrier and preserves the integrity of the physical intestinal barrier by regulating the expression of tight junction proteins, creating an acidic environment in the intestinal lumen, and producing mucin-related peptides [14,21].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Sekirov, 2010, Gut microbiota in health and disease, Physiol Rev source

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    • cites [21] Kim, 2018, Immune regulation by microbiome metabolites, Immunology source

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    Interpretationreasoning

    In chronic constipation, glucagon-like peptides are reduced, and intestinal transmission function is inhibited, leading to further aggravation of constipation.

    “In cases of chronic constipation, glucagonlike peptides are reduced, and intestinal transmission function is inhibited, leading to further aggravation of constipation.”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning

    In chronic constipation, mucus in the intestinal lumen decreases, mucin expression decreases, the intestinal epithelial barrier becomes damaged, and bacterial exposure increases, which activates the intestinal immune system and exacerbates intestinal inflammation.

    “In chronic constipation, the mucus in the intestinal lumen decreases, the expression level of mucin decreases, the intestinal epithelial barrier becomes damaged, and bacterial exposure is increased, which in turn activates the intestinal immune system and exacerbates intestinal inf lammation.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Conversely, SCFAs can stimulate mucin secretion, regulate the neurochemical phenotype, and enhance the excitability of choline acetyltransferase-positive neurons, thereby improving constipation.

    “conversely, they can stimulate mucin secretion, regulate the neurochemical phenotype, and enhance the excitability of choline acetyltransferase-positive neurons, thereby improving constipation [17,33,34].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [17] Parthasarathy, 2016, Relationship between microbiota of the colonic mucosa vs Feces and symptoms, colonic transit, and methane production in female patients with chronic constipation, Gastroenterology source

      Not checked in the free run.

    • cites [33] Makizaki, 2021, Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis, PLoS One source

      Not checked in the free run.

    • cites [34] Yarullina, 2020, Characterization of gut contractility and microbiota in patients with severe chronic constipation, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    During chronic constipation, harmful bacteria in the intestinal lumen increase, and pattern recognition receptors expressed by intestinal cells recognize specific pathogenic microorganisms, leading to activation of the immune response to resist pathogenic bacteria, promotion of colonization of beneficial bacteria, and reduction of the rate of intestinal infection.

    “During chronic constipation, harmful bacteria in the intestinal lumen increase, and pattern recognition receptors expressed by intestinal cells can recognize specific pathogenic microorganisms, leading to activation of the immune response to resist pathogenic bacteria, promotion of the colonization of beneficial bacteria, and effective reduction of the rate of intestinal infection [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Raskov, 2016, Irritable bowel syndrome, the microbiota and the gut-brain axis, Gut Microbes source

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    Premisecitation

    Constipated patients often exhibit elevated levels of methane, and these levels are inversely correlated with transit times in the small intestine and colon.

    “Studies have shown that the most common type of methanogenic bacteria in the gut is Mycobacterium smegmatis and that constipated patients often exhibit elevated levels of methane [38]; these levels are inversely correlated with the transit times in the small intestine and colon [20,39].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [38] Wang, 2023, Microbiota regulation in constipation and colorectal cancer, World J Gastrointest Oncol source

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    • cites [20] Iancu, 2023, Revisiting the intestinal microbiome and its role in Diarrhea and constipation, Microorganisms source

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    • cites [39] Rezaie, 2017, Hydrogen and methane-based breath testing in gastrointestinal disorders: the north American consensus, Am J Gastroenterol source

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    Premisecitation

    The brain-gut-microbiota axis is a nonlinear, bidirectional feedback network involving the central nervous system, gut, and intestinal microbiota and plays a role in the physiological and pathological processes of the gastrointestinal tract.

    “The brain-gut-microbiota axis is a nonlinear, bidirectional feedback network that involves the central nervous system, gut, and intestinal microbiota and plays a role in the physiological and pathological processes of the gastrointestinal tract [29] (Figure 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Mayer, Chen S, The gut–brain axis

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    Premisecitation

    BAs can regulate intestinal motility, secretion, and absorption and prevent excessive proliferation of gut microbes, thereby maintaining the integrity of the intestinal mucosal barrier.

    “BAs possess the ability to regulate intestinal motility, secretion, and absorption as well as to prevent excessive proliferation of gut microbes, thereby maintaining the integrity of the intestinal mucosal barrier [12].”
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    • cites [12] Li, 2023, The gut microbiome and metabolites are altered and interrelated in patients with functional constipation, Front Microbiol source

      Not checked in the free run.

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    Premisecitation

    SCFAs can activate mucosal receptors connected to intestinal nerves, thereby mediating the secretion of glucagon-like peptide-1 and maintaining intestinal transmission.

    “they can also activate mucosal receptors connected to intestinal nerves, thereby mediating the secretion of glucagon-like peptide-1 and maintaining intestinal transmission [29,30].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] Mayer, Chen S, The gut–brain axis

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    • cites [30] Liu, 2022, Interaction between the gut microbiota and intestinal motility, Evid Based Complement Alternat Med source

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    Premisecitation

    Lactulose can induce the growth of probiotics such as bifidobacteria and lactobacilli, preventing and treating intestinal dysbiosis.

    “Among the commonly used prebiotics, including lactulose, lactulose oligosaccharides, and inulin, lactulose is the most wellknown one, which can induce the growth of probiotics, such as bifidobacteria and lactobacilli, to prevent and treat intestinal dysbiosis, and these microbiota and SCFAs produced by lactulose fermentation can reduce intestinal inf lammation, maintain intestinal homeostasis, and”
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    • cites [60] Naseer, 2020, Therapeutic effects of prebiotics on constipation: a schematic review, Curr Clin Pharmacol

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    Inulin is the most commonly used and effective prebiotic.

    “Inulin is the most commonly used and effective prebiotic, which, in addition to the basic effects of prebiotics mentioned above, can promote the growth of bifidobacteria, reduce the abundance of cholephiles, and facilitate the restoration of normal intestinal flora [59,60].”
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    • cites [59] Araújo, 2022, Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence, Front Nutr source

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    • cites [60] Naseer, 2020, Therapeutic effects of prebiotics on constipation: a schematic review, Curr Clin Pharmacol

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    Premisenone given

    No studies have reported on the efficacy of single and combination prebiotics or the optimal combination of prebiotics.

    “A 21-day study involving 61 patients with constipation confirmed the effect of prebiotics in improving spontaneous intestinal motility [61], but no studies have reported on the efficacy of single and combination prebiotics or the optimal combination of prebiotics.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Inulin can promote the growth of bifidobacteria, reduce the abundance of cholephiles, and facilitate the restoration of normal intestinal flora.

    “Inulin is the most commonly used and effective prebiotic, which, in addition to the basic effects of prebiotics mentioned above, can promote the growth of bifidobacteria, reduce the abundance of cholephiles, and facilitate the restoration of normal intestinal flora [59,60].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [59] Araújo, 2022, Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence, Front Nutr source

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    • cites [60] Naseer, 2020, Therapeutic effects of prebiotics on constipation: a schematic review, Curr Clin Pharmacol

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    Premisecitation

    Inactive probiotics and heat-inactivated probiotics are effective in improving constipation.

    “In addition, inactive probiotics and heat-inactivated probiotics have been shown to be effective in improving constipation [26,57], suggesting that they may have advantages over some live probiotics in terms of stability and safety for patients with compromised enterobacterial defenses of treatment.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] Pan, 2022, Crosstalk between the gut microbiome and colonic motility in chronic constipation: potential mechanisms and microbiota modulation, Nutrients source

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    • cites [57] Andresen, 2020, Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial, Lancet Gastroenterol Hepatol source

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    Premisecitation

    Microbiota and SCFAs produced by lactulose fermentation can reduce intestinal inflammation, maintain intestinal homeostasis, and improve intestinal motility.

    “Among the commonly used prebiotics, including lactulose, lactulose oligosaccharides, and inulin, lactulose is the most wellknown one, which can induce the growth of probiotics, such as bifidobacteria and lactobacilli, to prevent and treat intestinal dysbiosis, and these microbiota and SCFAs produced by lactulose fermentation can reduce intestinal inf lammation, maintain intestinal homeostasis, and”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [60] Naseer, 2020, Therapeutic effects of prebiotics on constipation: a schematic review, Curr Clin Pharmacol

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    Premisecitation

    Endogenous substances produced by gut microbes, such as SCFAs, secondary BAs, and tryptophan metabolites, act as signaling molecules on enteroendocrine cells, enterochromaffin cells, and mucosal immune systems; these interactions affect the central nervous system through neuroimmune and neuroendocrine mechanisms, typically involving the vagus nerve.

    “Endogenous substances produced by gut microbes, such as SCFAs, secondary BAs, and tryptophan metabolites, act as signaling molecules on enteroendocrine cells, enterochromaffin cells, and mucosal immune systems.These interactions then affect the central nervous system through neuroimmune and neuroendocrine mechanisms, typically involving the vagus nerve [24,37,46].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [24] Ahluwalia, 2021, A distinct faecal microbiota and metabolite profile linked to bowel habits in patients with irritable bowel syndrome, Cells source

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    • cites [37] Wang, 2021, Roles of gut microbiota and metabolites in pathogenesis of functional constipation, Evid Based Complement Alternat Med

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    • cites [46] Singh, 2016, Microbiota dysbiosis controls the neuroinflammatory response after stroke, J Neurosci source

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    Premisecitation

    Medications are extensively used in the management of chronic constipation, but require patients to have a high degree of compliance and a certain economic level.

    “Medications are extensively used in the management of chronic constipation, but require patients to have a high degree of compliance and a certain economic level [3,6,8].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Aziz, 2020, An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation, Expert Rev Gastroenterol Hepatol source

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    • cites [6] Lai, 2023, Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial, Gut Microbes source

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    • cites [8] Anthony, 2003, Chronic constipation, N Engl J Med

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  • May combine two claims.

    Premisecitation

    Substance P stored in visceral neurons stimulates smooth muscle contraction and amplifies visceral pain; when constipation occurs in central nervous system disorders, nerves containing SP are stimulated, leading to release of stored SP and resulting in abdominal pain.

    “In addition, substance P (SP) stored in visceral neurons stimulates smooth muscle contraction and amplifies visceral pain; when constipation occurs in central nervous system disorders, nerves containing SP are stimulated, leading to the release of stored SP and resulting in abdominal pain [8,22,27].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Anthony, 2003, Chronic constipation, N Engl J Med

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    • cites [22] Raskov, 2016, Irritable bowel syndrome, the microbiota and the gut-brain axis, Gut Microbes source

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    • cites [27] Dimidi, 2017, Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation, Adv Nutr source

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    Premisecitation

    Mertsalmi et al. found that Parkinson's patients with constipation had more nonmotor symptoms and a lower abundance of fecal Prevotella compared with patients without constipation, and they were also more likely to have occult epilepsy.

    “Mertsalmi et al. [51] found that Parkinson's patients with constipation had more nonmotor symptoms and a lower abundance of fecal Prevotella compared with patients without constipation, and they were also more likely to have occult epilepsy [42].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Mertsalmi, 2017, More than constipation - bowel symptoms in Parkinson’s disease and their connection to gut microbiota, Eur J Neurol source

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    • cites [42] Tap, 2017, Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome, Gastroenterology source

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  • May combine two claims.

    Premisecitation

    Prebiotics selectively stimulate the growth of one or several bacteria in the colon, thereby regulating intestinal microecology and increasing intestinal SCFA content, and they also stimulate intestinal production of 5-HT and improve colonic motility.

    “They selectively stimulate the growth of one or several bacteria in the colon, thereby regulating the intestinal microecology and increasing the content of intestinal SCFAs, and it also stimulates intestinal production of 5-HT and improves colonic motility [58,59].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [58] Skrzydło-Radomańska, 2020, The effectiveness of synbiotic preparation containing Lactobacillus and Bifidobacterium probiotic strains and short chain Fructooligosaccharides in patients with diarrhea predominant irritable bowel syndrome-a randomized double-blind, placebo-controlled study, Nutrients source

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    • cites [59] Araújo, 2022, Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence, Front Nutr source

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    Premisecitation

    A previous animal study has shown that increased serotonin synthesis can trigger intestinal motility by regulating the production of metabolites in indigenous sporogenes, resulting in functional constipation.

    “A previous study in animal models also has shown that increased serotonin synthesis can trigger intestinal motility by regulating the production of metabolites in indigenous sporogenes, resulting in functional constipation [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Lai, 2023, Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial, Gut Microbes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These mechanisms can enhance colonic motility in patients with chronic constipation, leading to improvements in stool hardness, defecation frequency, and abdominal distension symptoms.

    “These mechanisms can enhance colonic motility in patients with chronic constipation, leading to improvements in stool hardness, defecation frequency, and abdominal distension symptoms.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Some studies have found that the concentration of serotonin in the plasma of platelets in patients with functional constipation tends to increase.

    “However, some studies have found that the concentration of serotonin in the plasma of platelets in patients with functional constipation tends to increase.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Lai, 2023, Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial, Gut Microbes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    FMT is currently not considered the preferred option for most patients and may be more suitable for those who do not respond to conventional treatments.

    “As a result, FMT is currently not considered the preferred option for most patients and may be more suitable for those who do not respond to conventional treatments [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Iancu, 2023, Revisiting the intestinal microbiome and its role in Diarrhea and constipation, Microorganisms source

      Not checked in the free run.

    • Rests on an assumption: FMT has limitations including cost and complexity of the procedure, unclear long-term efficacy and safety, and uncertainty of its impact on the recipient's immune system.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The neurotransmitter 5-HT is involved in the modulation of intestinal motility, secretion, and sensory conduction in patients with constipation.

    “The neurotransmitter 5-HT, which regulates the gastrointestinal tract, is also involved in the modulation of intestinal motility, secretion, and sensory conduction in patients with constipation.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Bifidobacterium and Lactobacillus are commonly used probiotics, and inulin is commonly used as a prebiotic.

    “Bifidobacterium and Lactobacillus are commonly used probiotics, and inulin is commonly used as a prebiotic [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Araújo, 2022, Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence, Front Nutr source

      Not checked in the free run.

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

    Premisenone given

    The causal relationships among intestinal dysbiosis, constipation, and neurological diseases are still unclear.

    “However, the causal relationships among intestinal dysbiosis, constipation, and neurological diseases are still unclear, and future human studies are needed to explore the underlying causes of intestinal dysbiosis and related diseases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    The gut microbiota and its regulation of the brain-gut-microbiota axis may become a new direction for the diagnosis and treatment of chronic constipation.

    “In conclusion, the gut microbiota and its regulation of the brain-gut-microbiota axis may become a new direction for the diagnosis and treatment of chronic constipation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The gut microbiota can influence the secretory and hormonal environment of the intestine, and specific microbial metabolites and signaling pathways are key players in microbiome-mediated intestinal function.

    “In addition, the gut microbiota has the ability to inf luence the secretory and hormonal environment of the intestine, and specific microbial metabolites and specific signaling pathways are key players in microbiome-mediated intestinal function.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    High heterogeneity of individual bacterial intestinal groups, differences in individual constipation states, and different strain-specific effects have led to a lack of consensus on the therapeutic efficacy of probiotics.

    “Probiotics have emerged as a”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In humans, synbiotics reduce colonic transit time, increase bowel frequency, improve stool consistency, and improve stool straining and incomplete bowel movements.

    “In humans, synbiotics have been shown to reduce colonic transit time, increase bowel frequency, improve stool consistency, and improve stool straining and incomplete bowel movements [59,62].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [59] Araújo, 2022, Probiotics, prebiotics, and synbiotics in chronic constipation: outstanding aspects to be considered for the current evidence, Front Nutr source

      Not checked in the free run.

    • cites [62] Yu, 2017, Effects of prebiotics and synbiotics on functional constipation, Am J Med Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    The gut microbiota is a central mediator in the brain-gut axis, and there are bidirectional interactions among the brain, gut, and gut microbes.

    “Furthermore, the gut microbiota is a central mediator in the brain-gut axis, and numerous studies have confirmed the bidirectional interactions among the brain, gut, and gut microbes.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Probiotics have emerged as a promising treatment option for chronic constipation in recent years.

    “Probiotics have emerged as a”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The gut microbiota plays a crucial role in the development and progression of constipation by interacting with the immune system, enteric nervous system, and central nervous system.

    “The gut microbiota plays a crucial role in the development and progression of constipation by interacting with the immune system, enteric nervous system, and central nervous system.”
    Quote in the paperNot a substantial claim
47 of 47

  • The paper relies on this without support.

    FMT has limitations including cost and complexity of the procedure, unclear long-term efficacy and safety, and uncertainty of its impact on the recipient's immune system.

    “At present, there are several factors that limit the widespread use of FMT, including the cost and complexity of the procedure itself, the unclear long-term efficacy and safety, and the uncertainty of its impact on the recipient's immune system.”

  • The paper relies on this without support.

    There is currently no highly effective cure for chronic constipation, and individual responses to existing treatments vary greatly.

    “Although various treatments exist for chronic constipation, individual responses vary greatly, and there is currently no highly effective cure.”
2 of 2

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.

  • The answer key reverses the stated effect of increased bile acids

    Minor

    The answer key calls increased bile-acid production a mechanism contributing to constipation, whereas the discussion says increased secondary bile-acid synthesis improves constipation symptoms.

  • A cited rat experiment is described as a mouse experiment

    Minor

    The discussion says the mixed-strain experiment used mice, but the title of its cited reference [55] specifies Sprague-Dawley rats.

  • Two different microbes are each called the most common methanogen

    Minor

    The text identifies both Clostridium spp. and Mycobacterium smegmatis as the most common methanogenic bacteria in the human gut.

  • Methane-transit correlation conflicts with the stated mechanism

    Minor

    An inverse correlation means higher methane levels accompany shorter transit times, while the proposed mechanism says methane weakens peristalsis and causes constipation. The text does not reconcile these opposing descriptions of methane's effect.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Anthony, 2003, Chronic constipation, N Engl J Med, 349
  2. Mayer, Chen S, The gut–brain axis, 73
  3. Tian, 2020, Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation. Zhonghua Wei Chang Wai Ke Za Zhi = Chinese, J Gastrointest Surg, 23, 63

Cited by

Sorted by citations

Related

Authors
Xu, X., Wang, Y., Long, Y., & Cheng, Y.
Affiliations
Beijing Hua Xin Hospital (CN)
Corresponding author
Cheng, Yanli
ORCID
Venue
Postgraduate Medical Journal
Publisher
Oxford University Press (OUP)
Published
2024-09-06
Volume
100
Issue
1190
Pages
890-897
ISSN
  • 0032-5473 (ISSN-L)
  • 1469-0756
DOI
10.1093/postmj/qgae112
OpenAlex
W4402326450
Cited by
32
References
62
Citations by year
2026: 22 · 2025: 8 · 2024: 2
FWCI
3.28
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • Postgraduate Medical Journal (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
chronic constipation, gut microbiota, gut dysbiosis, brain-gut-microbiota axis, probiotics, bowel movement regulation, microbial metabolites
MeSH terms
Gastrointestinal Microbiome, Brain-Gut Axis, Chronic Disease, Constipation, Humans, Probiotics, Dysbiosis

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 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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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