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Cited by 393Nutrition and Health in AgingGut microbiota and healthMuscle Physiology and Disorders

Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis

Open access
Grosicki, Gregory J., Fielding, Roger A., Lustgarten, Michael S.·2018·Calcified Tissue International
DOI 10.1007/s00223-017-0345-5PMC PMC5858871
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Abstract

Skeletal muscle is a highly plastic tissue that plays a central role in human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia) that is associated with a loss of independence and reduced quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as a potential contributor to age-associated muscle decline. Specifically, advancing age is characterized by a dysbiosis of gut microbiota that is associated with increased intestinal permeability, facilitating the passage of endotoxin and other microbial products (e.g., indoxyl sulfate) into the circulation. Upon entering the circulation, LPS and other microbial factors promote inflammatory signaling and skeletal muscle changes that are hallmarks of the aging muscle phenotype. This review will summarize existing literature suggesting cross-talk between gut microbiota and skeletal muscle health, with emphasis on the significance of this axis for mediating changes in aging skeletal muscle size, composition, and function.

AI snapshot

Written from the paper’s full text.

TL;DR

This review proposes a gut-muscle axis in which age-related gut dysbiosis increases intestinal permeability and circulating LPS/microbial metabolites, promoting inflammation and skeletal muscle atrophy, fat infiltration, and functional decline. It synthesizes murine and human evidence suggesting probiotics, prebiotics, and exercise may help mitigate sarcopenia.

Key findings

  • Aging is associated with a less diverse gut microbiota, reduced butyrate-producing bacteria and *Bifidobacterium*/*Lactobacillus*, and increased Proteobacteria/Enterobacteriaceae; these changes accompany increased intestinal permeability and elevated circulating LPS. In older humans, circulating LPS and skeletal muscle TLR4 expression/content were higher than in younger counterparts.
  • LPS and microbial metabolites promote muscle catabolism: high-fat-fed mice showed 2- to 3-fold elevated circulating LPS; LPS infusion induced pro-inflammatory cytokines and impaired glucose tolerance in wild-type but not CD-14 mutant mice. Indoxyl sulfate increased IL-6/TNF-α and atrophy markers (myostatin, atrogin-1) in cultured myocytes and increased atrogene expression with decreased muscle mass in mice.
  • Microbiota-targeted interventions affect muscle outcomes: *Lactobacillus reuteri* and *L. gasseri* decreased IL-6/MCP-1 and MuRF1/Atrogin-1 and increased tibialis anterior mass in leukemic mice; prebiotic oligofructose decreased circulating LPS/inflammation and increased muscle mass in obese mice; prebiotic inulin plus fructooligosaccharides increased handgrip strength and endurance in frail older adults.
  • Human observational links include frail advanced agers (n = 23; ~86 years) showing ~8-fold less *Lactobacillus* and ~6-fold more Enterobacteriaceae, and a larger older cohort (n = 178; ~78 years) in which community dwellers had more butyrate-producing microbes than long-stay residents; athletes had greater microbial diversity than healthy and overweight controls.

Methods

  • Design: narrative review of existing literature; no systematic review, meta-analysis, or primary data collection methods are stated.
  • Data/sample: synthesizes animal and human studies, including germ-free and conventional mice, high-fat diet models, leukemic/cachectic mice, obese mice, and human cohorts of older adults, frail elders, and athletes.
  • Main analysis: qualitative integration of findings to propose an endocrine gut-muscle communication axis linking age-related dysbiosis, intestinal permeability, circulating LPS/metabolites, inflammation, and skeletal muscle size, composition, and function.

Limitations

  • Stated: the authors note an inability to distinguish whether changes in microbiota are a driver or a product of compromised bone and muscle integrity; probiotic rescue in mice is cited as suggesting initiation, but causality remains unresolved.
  • Evident: as a narrative review, it lacks systematic search and quality appraisal and does not quantify pooled effects; much mechanistic evidence is from murine models, and human evidence is largely cross-sectional or associational, limiting causal inference.
  • Evident: several cited human studies are small (e.g., n = 23 frail agers) or observational, and the review states it could not identify any studies showing *Bifidobacterium* supplementation increases muscle mass.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s00223-017-0345-5

Cites

107 of 107 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 113 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Advancing age is characterized by a dysbiosis of gut microbiota.

    “In later years (> 65 years), however, the proclivity for aberrant changes in microbial composition appears to accelerate [13–15].”
    Quote in the paperSubstantial claim0 of 3 sources checked
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  • Interpretationreasoning

    The paper proposes a gut-muscle axis that plays a role in the age-related loss of muscle mass and function (sarcopenia).

    “To conclude, we will integrate these findings and propose a “gut-muscle axis” that we believe plays a role in the age-related loss of muscle mass and function (sarcopenia) [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    • Rests on an assumption: Findings from animal models (mice, rats, pigs) about gut microbiota and skeletal muscle can be generalized to humans.
  • Interpretationcitation

    An age-related increase in LPS levels might contribute to the greater occurrence of diabetes in older persons.

    “These findings suggest that an age-related increase in LPS levels might contribute to the greater occurrence of diabetes in older persons.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Excess nutrient uptake and storage (obesity) is associated with low microbial diversity and changes in the relative abundance of Bacteroidetes and Firmicutes.

    “excess nutrient uptake and storage (i.e., obesity) is associated with low microbial diversity and changes in the relative abundance of the major bacterial phyla (Bacteroidetes and Firmicutes) [27–29].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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  • Premisecitation

    Fecal microbiota transplant from obese humans into lean animals precipitated body composition shifts consistent with the phenotype of their donor.

    “who demonstrated that fecal microbiota transplant from obese humans into lean animals precipitated body composition shifts consistent with the phenotype of their donor”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    High-fat feeding is shown to compromise epithelial tight junctions and increase intestinal permeability.

    “high-fat feeding is shown to compromise epithelial tight junctions and increase intestinal permeability [34, 35]”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    High-fat feeding is known to induce chronic low-grade inflammation (e.g., IL-1, IL-6, and TNF-α elevation), a reported contributor to insulin resistance.

    “high-fat diet, which is known to induce chronic low-grade chronic inflammation (e.g., IL-1, IL-6, and TNF-α elevation), a reported contributor to insulin resistance [32, 33].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    High-fat fed mice exhibited an increase in body weight and inflammatory markers as well as a decrease in glucose tolerance.

    “As expected, high-fat fed mice exhibited an increase in body weight and inflammatory markers as well as a decrease in glucose tolerance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    In humans inoculated with LPS, endotoxin-mediated reductions in glucose tolerance are shown, evidenced by significant increases in skeletal muscle NF-κβ binding activity and JNK phosphorylation, which synergistically inhibit insulin signaling.

    “Endotoxin-mediated reductions in glucose tolerance have been similarly shown in humans inoculated with LPS, as evidenced by significant increases in skeletal muscle NF-κβ binding activity and JNK phosphorylation, which synergistically inhibit insulin signaling [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    The composition of gut microbiota is dynamic throughout the lifespan, undergoing rapid changes from birth until about 3 years of age, after which greater stability is established.

    “The composition of gut microbiota is shown to be dynamic throughout the lifespan, undergoing rapid changes from birth until ~ 3 years of age, after which greater stability is established [11, 12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Gut ecology is associated with cancer, cardiovascular disease, obesity, diabetes, and muscle wasting.

    “associations between gut ecology and cancer [16], cardiovascular disease [17], obesity [6], diabetes [18], and muscle wasting [19]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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  • May combine two claims.

    Premisecitation

    In older individuals, circulating LPS and skeletal muscle TLR4 gene expression and protein content were higher, and insulin sensitivity (quantified by HOMA-IR) was lower than in younger counterparts.

    “in older individuals circulating LPS and skeletal muscle TLR4 (a receptor for LPS [43]) gene expression and protein content were higher, and insulin sensitivity (quantified by HOMA-IR) was lower than their younger counterparts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Gut microbiota are emerging as a salient contributor to human health and disease, with effects particularly pronounced in older years.

    “Gut microbiota are emerging as a salient contributor to human health and disease [5], and their effects are particularly pronounced in older years [20].”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • May combine two claims.

    Interpretationcitation

    Circulating LPS, a prominent component of gut microbiota, induces skeletal muscle inflammation and insulin resistance, thereby contributing to the development of metabolic syndrome.

    “These studies and others [30, 37], show that circulating LPS, a prominent component of gut microbiota, induces skeletal muscle inflammation and insulin resistance thereby contributing to the development of metabolic syndrome.”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Premisecitation

    In response to indoxyl sulfate, C2C12 myoblasts exhibit an up-regulation of glycolysis and an increase in the activity of the pentose phosphate pathway.

    “in response to the gut microbiota-specific metabolite indoxyl sulfate [38], C2C12 myoblasts exhibit an up-regulation of glycolysis and an increase in the activity of the pentose phosphate pathway [39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • May combine two claims.

    Premisecitation

    TNF-α and IL-6 are strongly induced by circulating LPS and elevated in aging individuals.

    “TNF-α and IL-6 are strongly induced by circulating LPS [53] and elevated in aging individuals [54, 55].”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    Adipose tissue infiltration in skeletal muscle has been shown to increase with age and is associated with mobility impairment.

    “adipose tissue infiltration in skeletal muscle (i.e., change in muscle composition) has been shown to increase with age [81] and is associated with mobility impairment [82].”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • May combine two claims.

    Interpretationreasoning

    Coupling of microbial alterations with restoration of intestinal homeostasis and a reduction in muscle wasting suggests that Lactobacillus and Bifidobacterium may influence gut-muscle communication and regulate muscle size.

    “Coupling of these microbial alterations with restoration of intestinal homeostasis (e.g., increase tight junction proteins) and a reduction in muscle wasting suggests that Lactobacillus and Bifidobacterium may influence gut-muscle communication and regulate muscle size.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from animal models (mice, rats, pigs) about gut microbiota and skeletal muscle can be generalized to humans.

  • May combine two claims.

    Premisecitation

    In the same rats, there was an increase in circulating inflammatory cytokines (IL-6, TNF-α, and MCP-1) and intramuscular fat after just 3 days.

    “the authors reported an increase in circulating inflammatory cytokines (IL-6, TNF-α, and MCP-1) and intramuscular fat after just 3 days [85]”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • May combine two claims.

    Premisecitation

    Indoxyl sulfate, which is shown to increase with age, is reported to induce inflammatory cytokine expression (IL-6 and TNF-α) and markers of muscle atrophy (myostatin and atrogin-1) similar to that of LPS in cultured myocytes.

    “the tryptophan derivative indoxyl sulfate, which is similarly shown to increase with age [60], is reported to induce inflammatory cytokine expression (IL-6 and TNF-α) and markers of muscle atrophy (myostatin and atrogin-1) similar to that of LPS in cultured myocytes [61].”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Sepsis is characterized by severe muscle wasting due to both increases in proteolytic degradation and reductions in protein synthesis.

    “sepsis, a life-threatening illness characterized by severe muscle wasting due to both increases in proteolytic degradation and reductions in protein synthesis [52].”
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    Premisecitation

    Obesity appears to exacerbate the progression of sarcopenia by compounding inflammatory burden, resulting in sarcopenic obesity.

    “obesity appears to exacerbate the progression of sarcopenia by compounding inflammatory burden [45], resulting in a state of sarcopenic obesity”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Prebiotic feeding favorably affected gut microbiota, evidenced by a shift in the ratio of Bacteroidetes/Firmicutes and increases in the levels of Lactobacillus and Bifidobacterium spp.

    “Follow-up analyses confirmed the favorable effect of prebiotic feeding on gut microbiota, as was evidenced by a shift in the ratio of Bacteroidetes/Firmicutes in addition to increases in the levels of Lactobacillus and Bifidobacterium spp. [66].”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A variety of phenomena have been proposed to contribute to the age-related heightened inflammatory state, including redox stress, immuno- and endocrine senescence, DNA damage, epigenetic modification, and a distortion of gut microbial homeostasis associated with increased levels of circulating endotoxin.

    “A variety of phenomena have been proposed to contribute to this age-related heightened inflammatory state including redox stress [46], immuno- and endocrine senescence [47, 48], DNA damage [49], epigenetic modification [50], and a distortion of gut microbial homeostasis [51] that is associated with increased levels of circulating endotoxin [42].”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • May combine two claims.

    Interpretationcitation

    An age-related decrease in gut Bifidobacterium content may underlie increases in circulating endotoxin that are shown to induce skeletal muscle atrophy.

    “an age-related decrease in gut Bifidobacterium content may underlie increases in circulating endotoxin that are shown to induce skeletal muscle atrophy [71].”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    • Rests on an assumption: Findings from animal models (mice, rats, pigs) about gut microbiota and skeletal muscle can be generalized to humans.

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    Premisecitation

    Macrophage production of TNF-α occurs early in the stress response and has been demonstrated to stimulate protein degradation and apoptosis in cultured cells.

    “Macrophage production of TNF-α is shown to occur early in the stress response, and has been demonstrated to stimulate protein degradation and apoptosis in cultured cells [56, 57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] Li YP, Chen Y, John J, Moylan J, Jin B, Mann DL, Reid MB (2005) TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J 19:362–370 source

      Not checked in the free run.

    • cites [57] Baxter GT, Kuo RC, Jupp OJ, Vandenabeele P, MacEwan DJ (1999) Tumor necrosis factor-alpha mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression. J Biol Chem 274:9539–9547 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bifidobacterium are shown to decrease with age and are associated with lower intestinal and circulating LPS levels.

    “Bifidobacterium are shown to decrease with age [68], and are associated with lower intestinal [69] and circulating LPS levels [70].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [68] Enck P, Zimmermann K, Rusch K, Schwiertz A, Klosterhalfen S, Frick JS (2009) The effects of ageing on the colonic bacterial microflora in adults. Z Gastroenterol 47:653–658 source

      Not checked in the free run.

    • cites [69] Griffiths EA, Duffy LC, Schanbacher FL, Qiao H, Dryja D, Leavens A, Rossman J, Rich G, Dirienzo D, Ogra PL (2004) In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig Dis Sci 49:579–589 source

      Not checked in the free run.

    • cites [70] Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM (2007) Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50:2374–2383 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In young rats subjected to a high-fat high-sucrose diet, there was an increase in Enterobacteriaceae and a decrease in the abundance of Lactobacillus spp., changes similarly reported with aging.

    “Collins et al. subjected young rats to a high-fat high-sucrose diet and found an increase in Enterobacteriaceae (gram-negative member of the Proteobacteria phylum) and a decrease in the abundance of Lactobacillus spp., changes that have been similarly reported with aging [83, 84].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [83] Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5:e10667 source

      Not checked in the free run.

    • cites [84] van Tongeren S, Slaets J, Harmsen H, Welling G (2005) Fecal microbiota composition and frailty. Appl Environ Microbiol 71:6438–6442 source

      Not checked in the free run.

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

    Premisecitation

    Aging muscle appears to undergo a fast-to-slow fiber-type shift, hypothesized to reduce whole muscle power and increase fall risk.

    “aging muscle appears to undergo a fast-to-slow fiber-type shift [91], that is hypothesized to reduce whole muscle power and increase fall risk [92, 93].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [91] Larsson L, Grimby G, Karlsson J (1979) Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol Respir Environ Exerc Physiol 46:451–456

      Not checked in the free run.

    • cites [92] Korhonen MT, Cristea A, Alen M, Hakkinen K, Sipila S, Mero A, Viitasalo JT, Larsson L (1985) Suominen H (2006) Aging, muscle fiber type, and contractile function in sprint-trained athletes. J Appl Physiol 101:906–917 source

      Not checked in the free run.

    • cites [93] Reid KF, Fielding RA (2012) Skeletal muscle power: a critical determinant of physical functioning in older adults. Exerc Sport Sci Rev 40:4–12 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Administration of a synbiotic containing inulin-type fructans and Lactobacillus reuteri was shown to reverse increases in Escherichia and promoted proliferation of Lactobacillus and Bifidobacterium in leukaemic mice.

    “administration of a synbiotic containing inulin-type fructans and Lactobacillus reuteri was shown to reverse increases in Escherichia and promoted proliferation of Lactobacillus and Bifidobacterium in leukaemic mice [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Bindels LB, Neyrinck AM, Claus SP, Le Roy CI, Grangette C, Pot B, Martinez I, Walter J, Cani PD, Delzenne NM (2016) Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia. ISME J 10:1456–1470 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    LPS-associated cytokines can determinately affect protein equilibrium (synthesis and breakdown), and elevated endotoxin levels with age may contribute to reductions in muscle mass.

    “these findings demonstrate the ability of LPS-associated cytokines to determinately affect protein equilibrium (i.e., synthesis and breakdown), and suggest that elevated endotoxin levels with age may contribute to reductions in muscle mass.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In obese mice fed the prebiotic fiber oligofructose, there was a decrease in circulating LPS and inflammation and an increase in muscle mass.

    “Cani et al., who showed a decrease in circulating LPS and inflammation and an increase in muscle mass in obese mice fed the prebiotic fiber oligofructose [65].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58:1091–1103 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In leukemic mice, oral probiotic containing Lactobacillus reuteri and L. gasseri appeared to decrease serum levels of inflammatory cytokines (IL-6 and MCP-1) and atrogene expression (MuRF1 and Atrogin-1) in conjunction with an increase in mass of the tibialis anterior.

    “the leukemic mice were given an oral probiotic containing Lactobacillus reuteri and L. gasseri that appeared to decrease serum levels of inflammatory cytokines (IL-6 and MCP-1) and atrogene expression (MuRF1 and Atrogin-1) in conjunction with an increase in mass of the tibialis anterior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Bindels LB, Beck R, Schakman O, Martin JC, de Backer F, Sohet FM, Dewulf EM, Pachikian BD, Neyrinck AM, Thissen JP, Verrax J, Calderon PB, Pot B, Grangette C, Cani PD, Scott KP, Delzenne NM (2012) Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model. PLoS ONE 7:1–10 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Age-related changes in skeletal muscle size and composition summate to yield reductions in skeletal muscle function (strength and power) that ultimately affect physical performance and the ability to live independently.

    “Age-related changes in skeletal muscle size and composition summate to yield reductions in skeletal muscle function (strength and power) [77] that ultimately affect physical performance and the ability to live independently [95].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [77] Reid KF, Naumova EN, Carabello RJ, Phillips EM, Fielding RA (2008) Lower extremity muscle mass predicts functional performance in mobility-limited elders. J Nutr Health Aging 12:493–498 source

      Not checked in the free run.

    • cites [95] Bean JF, Leveille SG, Kiely DK, Bandinelli S, Guralnik JM, Ferrucci L (2003) A comparison of leg power and leg strength within the InCHIANTI study: which influences mobility more? J Gerontol A Biol Sci Med Sci 58:728–733 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Comparison of microbial diversity among elite rugby players and healthy normal weight and overweight age-matched controls elicited a hierarchical pattern (athletes > healthy > overweight), suggesting an association between microbial diversity, body composition, and physical function.

    “Comparison of microbial diversity among these athletes and both healthy normal weight (BMI ≤ 25) and overweight (BMI ≥ 28) age-matched controls elicited a hierarchical pattern (athletes > healthy > overweight), suggesting an association between microbial diversity, body composition, and physical function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Clarke SF, Murphy EF, O’Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O’Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O’Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD (2014) Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63:1913–1920 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Transfer of gut microbiota from an obese pig to a GF mouse replicated the host myocellular phenotype, which mirrored that of aging skeletal muscle (fast fiber atrophy concomitant with a fast-to-slow fiber type shift).

    “transfer of gut microbiota from an obese pig to a GF mouse replicated the host myocellular phenotype, which mirrored that of aging skeletal muscle (i.e., fast fiber atrophy concomitant with a fast-to-slow fiber type shift).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Yan H, Diao H, Xiao Y, Li W, Yu B, He J, Yu J, Zheng P, Mao X, Luo Y, Zeng B, Wei H, Chen D (2016) Gut microbiota can transfer fiber characteristics and lipid metabolic profiles of skeletal muscle from pigs to germ-free mice. Sci Rep 6:31786 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Beneficial changes in gut health seen with exercise training implicate skeletal muscle contraction as a regulator of microbial composition, and provide evidence for bi-directional gut-muscle effects.

    “The beneficial changes in gut health seen with exercise training implicate skeletal muscle contraction as a regulator of microbial composition, and provide evidence for bi-directional gut-muscle effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Butyrate is shown to enhance intestinal barrier function by reinforcing tight junction assembly, which in theory should prevent endotoxin translocation and reduce circulating inflammation.

    “butyrate is shown to enhance intestinal barrier function by reinforcing tight junction assembly [96], which, in theory, should prevent endotoxin translocation and reduce circulating inflammation [97].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [96] Peng L, Li ZR, Green RS, Holzman IR, Lin J (2009) Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr 139:1619–1625 source

      Not checked in the free run.

    • cites [97] Cox MA, Jackson J, Stanton M, Rojas-Triana A, Bober L, Laverty M, Yang X, Zhu F, Liu J, Wang S, Monsma F, Vassileva G, Maguire M, Gustafson E, Bayne M, Chou CC, Lundell D, Jenh CH (2009) Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J Gastroenterol 15:5549–5557 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Investigations of age-related changes in gut microbiota describe a bacterial community that is both less diverse and lacking in microorganisms responsible for the production of butyrate, and more abundant in pathogens belonging to the Proteobacteria phylum (e.g., Enterobacteriaceae).

    “investigations of age-related changes in gut microbiota describe a bacterial community that is both less diverse and lacking in microorganisms responsible for the production of butyrate (indicative of gastrointestinal health) [15, 84, 98, 99], and more abundant in pathogens belonging to the Proteobacteria phylum (e.g., Enterobacteriaceae) [15, 68, 83].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [15] Rampelli S, Candela M, Turroni S, Collino EB, Franceschi C, O’Toole PW, Brigidi P (2013) Functional metagenomic profiling of intestinal microbiome in extreme ageing. Aging 5:902–912 source

      Not checked in the free run.

    • cites [84] van Tongeren S, Slaets J, Harmsen H, Welling G (2005) Fecal microbiota composition and frailty. Appl Environ Microbiol 71:6438–6442 source

      Not checked in the free run.

    • cites [98] Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 9:178–184 source

      Not checked in the free run.

    • cites [99] Jeffery IB, Lynch DB, O’Toole PW (2016) Composition and temporal stability of the gut microbiota in older persons. ISME J 10:170–182 source

      Not checked in the free run.

    • cites [68] Enck P, Zimmermann K, Rusch K, Schwiertz A, Klosterhalfen S, Frick JS (2009) The effects of ageing on the colonic bacterial microflora in adults. Z Gastroenterol 47:653–658 source

      Not checked in the free run.

    • cites [83] Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5:e10667 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Associated with these age-related microbial changes is a decrease in the integrity of epithelial tight junctions and increased intestinal permeability, facilitating the translocation of microbial byproducts into circulation.

    “Associated with these changes is a decrease in the integrity of epithelial tight junctions and increased intestinal permeability [14], facilitating the translocation of microbial byproducts into circulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JDL, Maggie J, Davidson DJ, Verd EF, Surette MG, Bowdish D (2017) Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21:455–466 source

      Not checked in the free run.

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

    Premisenone given

    Research in murine models has begun to identify microbial targets with likely skeletal muscle ramifications.

    “Research in murine models has begun to identify microbial targets with likely skeletal muscle ramifications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Exercise training is an effective means to promote beneficial changes in gut microbial health that seem to reduce circulating inflammation and support the maintenance of muscle mass and function.

    “these findings advocate that exercise training is an effective means to promote beneficial changes in gut microbial health that seem to reduce circulating inflammation and support the maintenance of muscle mass and function.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from animal models (mice, rats, pigs) about gut microbiota and skeletal muscle can be generalized to humans.

  • May combine two claims.

    Premisecitation

    Institutionalized elderly had a greater abundance of Enterobacteriaceae and Escherichia/Shigella, and less gut microbial diversity when compared with community dwellers.

    “institutionalized elderly had a greater abundance of Enterobacteriaceae and Escherichia/Shigella, and less gut microbial diversity when compared with the community dwellers.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 9:178–184 source

      Not checked in the free run.

38 of 38

  • The paper relies on this without support.

    Findings from animal models (mice, rats, pigs) about gut microbiota and skeletal muscle can be generalized to humans.

    “Taken together, these studies suggest a link between Lactobacillus species and skeletal muscle size that is worthy of further investigation in humans.”
    “These findings highlight the possibility that gut microbiota can transfer muscle fiber characteristics, and open the door for studies investigating the transplant of microbiota from young to old as a means to improve skeletal muscle size and composition.”

  • The paper relies on this without support.

    Age-related changes in gut microbiota observed in cross-sectional studies reflect aging rather than cohort or environmental differences.

    “Although the underlying cause(s) (host vs environment) of this apparent age-related microbial imbalance have yet to be defined”
    “While changes in gut microbiota can be attributed to either host (genetics, age) or environmental (activity, diet) factors, we have focused on microbial dynamics with organismal aging.”

  • The paper relies on this without support.

    Microbial targets identified in murine models have ramifications for human skeletal muscle.

    “Research in murine models has begun to identify microbial targets with likely skeletal muscle ramifications.”
    “These findings lay the framework for strategic human interventions aiming to manipulate microbial ecology as a means to benefit skeletal muscle health and extend healthy life years in a rapidly expanding aging population.”
3 of 3

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Authors
Grosicki, G. J., Fielding, R. A., & Lustgarten, M. S.
Affiliations
Tufts University (US)
Corresponding author
Lustgarten, Michael S.
ORCID
Venue
Calcified Tissue International
Publisher
Springer Science and Business Media LLC
Published
2017-10-20
Volume
102
Issue
4
Pages
433-442
ISSN
  • 0171-967X (ISSN-L)
  • 1432-0827
DOI
10.1007/s00223-017-0345-5
PMC
PMC5858871
OpenAlex
W2765923427
Cited by
388
References
106
Citations by year
2026: 39 · 2025: 52 · 2024: 67 · 2023: 44 · 2022: 46 · 2021: 44 · 2020: 52 · 2019: 31 · 2018: 12 · 2017: 1
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Calcified Tissue International (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Agriculture (58-1950-4-003)
  • National Institute on Aging (5K01AG050700-02)
Topics
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
gut microbiota, gut-muscle axis, sarcopenia, skeletal muscle aging, muscle mass, muscle composition, muscle function, dysbiosis, intestinal permeability, lipopolysaccharide, indoxyl sulfate, inflammation, muscle plasticity
MeSH terms
Gastrointestinal Microbiome, Age Factors, Animals, Biological Products, Humans, Muscle, Skeletal, Gastrointestinal Tract, 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 2026-10-10.

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

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