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Cited by 901Gut microbiota and healthAntibiotic Use and ResistanceOral microbiology and periodontitis research

Antibiotic-Induced Changes in the Intestinal Microbiota and Disease

Open access
Becattini, Simone, Taur, Ying, Pamer, Eric G.·2016·Trends in Molecular Medicine
DOI 10.1016/j.molmed.2016.04.003PMC PMC4885777
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Abstract

The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents. Here we review the most recently discovered connections between host pathophysiology, microbiota, and antibiotics highlighting technological platforms, mechanistic insights, and clinical strategies to enhance resistance to diseases by preserving the beneficial functions of the microbiota.

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Crossref · 10.1016/j.molmed.2016.04.003

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  • Premisecitation

    The gut microbiota influences many physiological and pathological processes in humans.

    “Although the physiology of virtually all organs is influenced by the microbiota [5, 6]”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Premisecitation

    Commensal bacteria synthesize key molecules needed for tissue development.

    “commensals protect from pathogen invasion, extract additional energy from food, synthesize key molecules for tissue development”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Walter J Ley R The human gut microbiome: ecology and recent evolutionary changes Annual review of microbiology 2011 65 411 429 21682646 source

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    • cites [3] Brestoff JR Artis D Commensal bacteria at the interface of host metabolism and the immune system Nature immunology 2013 14 676 684 23778795 PMC4013146 source

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    • cites [4] Buffie CG Pamer EG Microbiota-mediated colonization resistance against intestinal pathogens Nature reviews. Immunology 2013 13 790 801 PMC4194195 24096337 source

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  • Premisecitation

    Commensal bacteria extract additional energy from food.

    “commensals protect from pathogen invasion, extract additional energy from food, synthesize key molecules for tissue development”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Walter J Ley R The human gut microbiome: ecology and recent evolutionary changes Annual review of microbiology 2011 65 411 429 21682646 source

      Not checked in the free run.

    • cites [3] Brestoff JR Artis D Commensal bacteria at the interface of host metabolism and the immune system Nature immunology 2013 14 676 684 23778795 PMC4013146 source

      Not checked in the free run.

    • cites [4] Buffie CG Pamer EG Microbiota-mediated colonization resistance against intestinal pathogens Nature reviews. Immunology 2013 13 790 801 PMC4194195 24096337 source

      Not checked in the free run.

  • Premisecitation

    Commensal bacteria protect the host from pathogen invasion.

    “commensals protect from pathogen invasion, extract additional energy from food, synthesize key molecules for tissue development”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2] Walter J Ley R The human gut microbiome: ecology and recent evolutionary changes Annual review of microbiology 2011 65 411 429 21682646 source

      Not checked in the free run.

    • cites [3] Brestoff JR Artis D Commensal bacteria at the interface of host metabolism and the immune system Nature immunology 2013 14 676 684 23778795 PMC4013146 source

      Not checked in the free run.

    • cites [4] Buffie CG Pamer EG Microbiota-mediated colonization resistance against intestinal pathogens Nature reviews. Immunology 2013 13 790 801 PMC4194195 24096337 source

      Not checked in the free run.

  • Premisecitation

    Oral administration of lipopolysaccharide reverses antibiotic-induced susceptibility to vancomycin-resistant enterococcus infection in mice.

    “a defect that can be reverted by oral administration of LPS [18]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Brandl K Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits Nature 2008 455 804 807 18724361 PMC2663337 source

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  • May combine two claims. 82
  • Classified as probably not a substantial claim. 4

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    Premisecitation

    Mice reconstituted with SFB-lacking microbiota have a reduced intestinal Th17 compartment and are more susceptible to Clostridium rodentium challenge.

    “Mice reconstituted with SFB-lacking microbiota develop a reduced intestinal Th17 compartment and are therefore more susceptible to Clostridium rodentium challenge, a model for human enterohemorrhagic infections [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Ivanov II Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine Cell host & microbe 2008 4 337 349 18854238 PMC2597589 source

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    Premisecitation

    Antibiotic treatment perturbs the basophil compartment in mouse blood and bone marrow through a Th2-IL-4-IgE pathway, leading to exacerbated allergic syndromes.

    “antibiotic-treatment perturbs the basophil compartment in the blood and BM of mice by acting through a Th2-IL-4-IgE pathway, which leads to exacerbated allergic syndromes [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Hill DA Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation Nature medicine 2012 18 538 546 PMC3321082 22447074 source

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    Premisecitation

    Perinatal antibiotic exposure alters neutrophil number and function by impairing G-CSF and IL-17 production, increasing neonatal risk of sepsis from E. coli or Klebsiella pneumonia.

    “perinatal antibiotic exposure alters neutrophil number and functions by impairing G-CSF and IL-17 production, predisposing neonates to increased risk of E. coli or Klebsiella pneumonia-induced sepsis [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Commensal sensing by lamina propria-resident phagocytes promotes release of retinoic acid and IL-10 in mice, leading to generation and expansion of regulatory T cells, important for tolerance to food antigens.

    “Commensal sensing by LP-resident phagocytes promotes release of retinoic acid (RA) and IL-10 in mice, leading to the generation and expansion of Tregs, a mechanism that is important in establishing tolerance to food antigens [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Mortha A Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis Science 2014 343 1249288 24625929 PMC4291125 source

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    Premisecitation

    Antibiotics impair immunity against lymphocytic choriomeningitis virus in mice by lowering expression of antiviral genes Ifnb and Irf7 in lung macrophages, causing defects in CD8+ T cell expansion and IFN-γ/TNF-α and IgG production.

    “Antibiotics have been shown to impair immunity against lymphocytic choriomeningitis virus (LCMV) in mice, by lowering the expression of antiviral genes such as Ifnb and Irf7 in lung macrophages, resulting in defects in CD8+ T cell expansion, as well as in IFN-γ/TNF-α and IgG production [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Abt MC Commensal bacteria calibrate the activation threshold of innate antiviral immunity Immunity 2012 37 158 170 22705104 PMC3679670 source

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    Premisecitation

    Commensal Clostridia clusters IV and XIVa promote accumulation of regulatory T cells in the colon by increasing TGF-β production in intestinal epithelial cells, protecting mice from DSS-induced colitis and strengthening oral tolerance.

    “Commensal Clostridia belonging to clusters IV and XIVa have been shown to promote accumulation of Tregs in the colon by increasing TGF-β production in IECs, thus protecting mice from DSS-induced colitis and strengthening oral tolerance [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Atarashi K Induction of colonic regulatory T cells by indigenous Clostridium species Science 2011 331 337 341 21205640 PMC3969237 source

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    Premisecitation

    In that influenza model, immunoglobulin levels, T cell numbers and IFN-γ production are affected, resulting in increased viral titers.

    “Immunoglobulin levels, T cell numbers and IFN-γ production were consequently affected, resulting in increased viral titers.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Ichinohe T Microbiota regulates immune defense against respiratory tract influenza A virus infection Proceedings of the National Academy of Sciences of the United States of America 2011 108 5354 5359 21402903 PMC3069176 source

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    Premisecitation

    Germ-free mice have aberrant spleen architecture, fewer CD4+ T lymphocytes in lymphoid organs, and an increased Th2/Th1 ratio.

    “GF mice exhibit aberrant spleen architecture, decreased numbers of CD4+ T lymphocytes in lymphoid organs, and an increased Th2/Th1 ratio [28].”
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    • cites [28] Mazmanian SK An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system Cell 2005 122 107 118 16009137 source

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    Premisecitation

    Short-term antibiotic treatment impairs RegIII-γ expression in mice and makes them susceptible to vancomycin-resistant enterococcus infection.

    “even short-term antibiotic treatment impairs its expression, rendering mice susceptible to vancomycin-resistant enterococcus (VRE) infection”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Brandl K Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits Nature 2008 455 804 807 18724361 PMC2663337 source

      Not checked in the free run.

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    Premisecitation

    Th17 differentiation in the small intestine lamina propria depends on the microbiota; germ-free mice have a reduced Th17 compartment that is restored by fecal material from conventional mice.

    “Th17 differentiation in the small intestine (SI) LP depends on the microbiota; GF mice have a reduced Th17 compartment that is restored by introduction of fecal material from conventional mice [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Ivanov II Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine Cell host & microbe 2008 4 337 349 18854238 PMC2597589 source

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    Premisecitation

    TLR5 signaling in dendritic cells induces IL-23, which promotes IL-22 release by innate lymphoid cells and RegIII-γ expression in intestinal epithelial cells.

    “Upon TLR5 signaling, DCs produce IL-23, promoting IL-22 release by innate lymphoid cells (ILCs) and therefore, RegIII-γ expression in intestinal epithelial cells (IECs) [19, 20].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Kinnebrew MA Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection The Journal of infectious diseases 2010 201 534 543 20064069 PMC2811237 source

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    • cites [20] Kinnebrew MA Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense Immunity 2012 36 276 287 22306017 PMC3288454 source

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  • May combine two claims.

    Interpretationreasoning

    Commensals can directly or indirectly protect against pathogens, and antibiotic use severely impairs this function, increasing host infection risk.

    “Thus, taken from these examples, it is clear that commensals can directly or indirectly protect from pathogens, and antibiotic use severely impairs this function, which in turn increases the risk of host infection.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    The microbiota can contribute to disease through production of noxious catabolites, overgrowth, sustaining inflammation, or supporting pathogens.

    “The microbiota can contribute to a variety of diseases through different mechanisms, including production of noxious catabolites, a capacity to overgrow, to sustain inflammation, or to provide support for pathogens.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Female NOD mice produce less short-chain fatty acids than male NOD mice; their CRAMP levels can be restored by conventionalization with male feces, resulting in protection from diabetes.

    “Female NOD mice displayed lower SCFA production than in male NOD mice, and their CRAMP levels could be restored by conventionalization with feces from males, resulting in protection from diabetes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Sun J Pancreatic beta-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota Immunity 2015 43 304 317 26253786 source

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    Premisecitation

    Diet profoundly influences gut microbiota composition and functions, and this effect can promote disease.

    “Diet profoundly influences gut microbiota composition and functions [57], an effect that can promote disease.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] David LA Diet rapidly and reproducibly alters the human gut microbiome Nature 2014 505 559 563 24336217 PMC3957428 source

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    Premisecitation

    TIV and other unadjuvanted vaccines induce IgG and IgM production in a TLR5-dependent manner through the microbiota in mice and possibly humans, as suggested by correlation between leukocyte TLR5 expression and anti-influenza antibody titers in vaccinees.

    “TIV (influenza trivalent inactivated) and other unadjuvanted vaccines were reported to induce IgG and IgM production in a TLR5-dependent manner through the microbiota in mice and, possibly, humans, as suggested by the correlation between leukocyte TLR5 expression levels and anti-influenza antibody titers in cohorts of vaccinees [48].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Oh JZ TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination Immunity 2014 41 478 492 25220212 PMC4169736 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Antibiotic treatment favors priming of diabetogenic T cells, promoting disease progression in NOD mice.

    “antibiotic treatment favored priming of diabetogenic T cells, thus promoting disease progression”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Sun J Pancreatic beta-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota Immunity 2015 43 304 317 26253786 source

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    Premisecitation

    Short-chain fatty acids drive CRAMP production in pancreatic β cells in mice, promoting a regulatory fate in macrophages and enhancing regulatory T cell priming.

    “SCFAs were reported to drive cathelicidin-related antimicrobial peptide (CRAMP) production in pancreatic β cells in mice, promoting a regulatory fate in macrophages, which enhanced the priming of Tregs [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Sun J Pancreatic beta-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota Immunity 2015 43 304 317 26253786 source

      Not checked in the free run.

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    Premisecitation

    The microbiota confers protection against pathogens, called colonization resistance, which antibiotic treatment can severely impair.

    “The microbiota can confer protection against pathogens, a phenomenon referred to as colonization resistance, which can be severely impaired by antibiotic treatment [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Buffie CG Pamer EG Microbiota-mediated colonization resistance against intestinal pathogens Nature reviews. Immunology 2013 13 790 801 PMC4194195 24096337 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a house dust mite model, mice fed a high fiber diet have increased circulating short-chain fatty acids; these prevent lung allergic inflammation by acting on GPR41 and promoting phagocytes with reduced Th2-polarizing capacity.

    “Mice fed a high fiber diet have shown increased levels of circulating SCFAs in a model of intranasal challenge with house dust mite (HDM) extract; the SCFAsprevented lung allergic inflammation by acting on the propionate receptor GPR41, and promoting the development of phagocytes with reduced Th2-polarizing capacity [46].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Trompette A Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis Nature medicine 2014 20 159 166 24390308 source

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    Premisecitation

    Personalized dietary interventions based on algorithm predictions significantly altered microbiota composition while improving glycemic control, suggesting that diet-based microbiome modulation could prevent diabetes-predisposing conditions.

    “personalized dietary interventions adopted on the basis of algorithm predictions, significantly altered microbiota composition while improving glycemic control, suggesting that modulation of microbiome configuration through diet could be used to prevent diabetes-predisposing conditions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Zeevi D Personalized Nutrition by Prediction of Glycemic Responses Cell 2015 163 1079 1094 26590418 source

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

    Premisecitation

    A correlation between certain bacterial taxa and type 2 diabetes has been proposed based on analyses of human gut metagenomes.

    “A correlation between certain bacterial taxa and type 2 diabetes has been proposed, based on analyses of human gut metagenomes [60, 61].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    • cites [61] Qin J A metagenome-wide association study of gut microbiota in type 2 diabetes Nature 2012 490 55 60 23023125 source

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    Premisecitation

    Androgens limit diabetes, possibly by reducing T cell proliferation and polarization toward a Th1 fate.

    “Androgens are in fact known to limit diabetes [43], possibly by reducing T cell proliferation and polarization towards a Th1 cell fate [44, 45].”
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    • cites [43] Fox HS Androgen treatment prevents diabetes in nonobese diabetic mice The Journal of experimental medicine 1992 175 1409 1412 1569406 PMC2119211 source

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    • cites [44] Roden AC Augmentation of T Cell Levels and Responses Induced by Androgen Deprivation The Journal of Immunology 2004 173 6098 6108 15528346 source

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    • cites [45] Kissick HT Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation Proceedings of the National Academy of Sciences of the United States of America 2014 111 9887 9892 24958858 PMC4103356 source

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    Premisecitation

    TIV-challenged antibiotic-treated and TLR5-deficient mice have defective antibody production, but flagellin administration restores the humoral response.

    “TIV-challenged antibiotic-treated (and TLR5-deficient, TLR5−/−) mice exhibited defective antibody production, but administration of the TLR5-agonist flagellin, restored the humoral response.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Oh JZ TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination Immunity 2014 41 478 492 25220212 PMC4169736 source

      Not checked in the free run.

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    Premisecitation

    Consumption of artificial sweeteners in mice and humans leads to deregulation of intestinal microbiota, with altered glycan degradation promoting decreased glucose tolerance, a pre-diabetic condition.

    “Consumption of artificial sweeteners in mice and humans has been shown to lead to deregulation of the intestinal microbiota, with altered glycan degradation capacity promoting decreased glucose tolerance, a pre-diabetic condition [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    In humans, recurrent C. difficile infection occurs in hospitalized patients, especially those receiving antibiotics, and causes diseases ranging from mild diarrhea to deadly toxic megacolon.

    “In humans, recurrent infection with C. difficile occurs in hospitalized patients, in particular those undergoing antibiotic treatment, causing diseases ranging from mild diarrhea to deadly toxic megacolon.”
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    • cites [53] van Nood E Duodenal infusion of donor feces for recurrent Clostridium difficile The New England journal of medicine 2013 368 407 415 23323867 source

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    Premisecitation

    Sensing of commensal-derived lipopolysaccharide is necessary for development of B1 cells in mouse spleen and for maintenance of basal circulating IgM, which protects in the cecal ligation and puncture sepsis model.

    “sensing of commensal-derived LPS has been shown to be necessary for the development of B1 cells in mouse spleen and for the maintenance of basal levels of circulating IgM, which exert a protective role in the cecal ligation and puncture (CLP)-induced sepsis model [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Colonization resistance operates through direct mechanisms not requiring host involvement and indirect mechanisms mediated by host response.

    “Colonization resistance takes place through direct (not requiring host involvement) or indirect mechanisms (ultimately mediated by the host response, as mentioned above for the modulation of AMPs) [18, 19].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Brandl K Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits Nature 2008 455 804 807 18724361 PMC2663337 source

      Not checked in the free run.

    • cites [19] Kinnebrew MA Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection The Journal of infectious diseases 2010 201 534 543 20064069 PMC2811237 source

      Not checked in the free run.

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    Premisecitation

    Metronidazole, but not streptomycin, reduces the thickness of the inner mucus layer in the large intestine in a NLRP6-dependent process and increases susceptibility to oral C. rodentium infection in mice.

    “Treatment with metronidazole, which selectively depletes anaerobes, but not streptomycin, reduced the thickness of the inner mucus layer in the large intestine (LI) – a process that depends on NLRP6 – and increased susceptibility to oral C. rodentium infection in mice [49, 50].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [49] Wlodarska M Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium-induced colitis Infection and immunity 2011 79 1536 1545 21321077 PMC3067531 source

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    Premisecitation

    Colonization resistance against C. difficile is present in healthy individuals, and transfer of healthy microbiota is currently used to treat recurrent infections.

    “Colonization resistance against C. difficile presents itself in healthy individuals, and transfer of healthy microbiota is currently being performed to treat patients with recurrent infections [53].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] van Nood E Duodenal infusion of donor feces for recurrent Clostridium difficile The New England journal of medicine 2013 368 407 415 23323867 source

      Not checked in the free run.

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    Premisecitation

    Reconstitution with C. scindens alone or within a bacterial consortium protects antibiotic-treated mice from C. difficile intestinal colonization.

    “Reconstitution with C. scindens alone or within a bacterial consortium, protected antibiotic-treated mice from C. difficile intestinal colonization.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Buffie CG Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile Nature 2015 517 205 208 25337874 PMC4354891 source

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    Premisecitation

    TLR5 signaling affects short-lived plasma cells, enhancing survival/differentiation and antibody production, and lymph node medullary cord macrophages, leading to production of plasma cell-sustaining factors TNF-α, IL-6, and APRIL.

    “TLR5 signaling had an effect on short-lived plasma cells, enhancing survival/differentiation and antibody production, as well as on lymph node (LN) medullary cord macrophages, leading to the production of plasma cell-sustaining factors such as TNF-α, IL-6, and APRIL.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Oh JZ TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination Immunity 2014 41 478 492 25220212 PMC4169736 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bifidobacterium longum protects mice from enterohemorrhagic E. coli O157 infection through short-chain fatty acids that prevent intestinal epithelial cell apoptosis and inflammation, preserve gut epithelium integrity, reduce Stx2 toxin spread into blood, and improve survival.

    “Bifidobacterium longum has been shown to protect mice from enterohemorrhagic E. coli O157 infection through the production of SCFAs, that prevent IEC apoptosis and inflammation, thus preserving gut epithelium integrity, and reducing the spread of Stx2 toxin into the bloodstream, ultimately improving host survival [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Fukuda S Bifidobacteria can protect from enteropathogenic infection through production of acetate Nature 2011 469 543 547 21270894 source

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    Premisecitation

    Low carbohydrate diet or treatment with selected antibiotics prevents polyp formation in this model.

    “low carbohydrate diet or treatment with selected antibiotics could prevent polyp formation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Belcheva A Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells Cell 2014 158 288 299 25036629 source

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    Premisecitation

    In vitro, B. thetaiotaomicron cleaves fucose from mucin and enhances virulence of E. coli.

    “In vitro, B. thetaiotaomicron can cleave off fucose from mucin and enhance virulence of E. coli.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [77] Pacheco AR Fucose sensing regulates bacterial intestinal colonization Nature 2012 492 113 117 23160491 PMC3518558 source

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    Premisecitation

    B. thetaiotaomicron carries sialidases that cleave sialic acid from mucus, although it lacks the enzymatic machinery to catabolize that sugar.

    “B. thetaiotaomicron also carries sialidases that can cleave sialic acid from mucus, although the bacterium lacks the enzymatic machinery necessary to catabolize such sugar [78].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Ng KM Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens Nature 2013 502 96 99 23995682 PMC3825626 source

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  • May combine two claims.

    Premisecitation

    Digoxin reduction by E. lenta is enhanced by other commensals but repressed by arginine, which can be supplemented through a high-protein diet.

    “This activity is enhanced in the presence of other commensals, but is repressed by arginine, which can be supplemented through a high-protein diet [72].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] Haiser HJ Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta Science 2013 341 295 298 23869020 PMC3736355 source

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  • May combine two claims.

    Premisecitation

    L-carnitine- or phosphatidylcholine-supplemented diets induce higher atheroma formation and wider aortic lesions in ApoE- mice, and disease is ameliorated by antibiotic treatment.

    “LC- or PC- supplemented diets were found to induce higher atheroma formation and wider aortic lesions in ApoE- mice, and disease was ameliorated by antibiotic treatment [68, 69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Koeth RA Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Nature medicine 2013 19 576 585 PMC3650111 23563705 source

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    • cites [69] Wang Z Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Nature 2011 472 57 63 21475195 PMC3086762 source

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  • May combine two claims.

    Premisecitation

    In conventional mice, antibiotics reduce commensals competing for sugars liberated before treatment, increasing nutrient availability and favoring pathogen expansion in a limited time window peaking at day 1 and ending at day 3 after antibiotic treatment.

    “In conventional mice, antibiotics reduce the amount of commensals competing for sugars liberated prior to treatment, increasing nutrient availability and favoring pathogen expansion througha limited time-window (peaking at day 1 and ending at day 3 post-antibiotic treatment for this study) [78].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Ng KM Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens Nature 2013 502 96 99 23995682 PMC3825626 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The microbiota can favor or amplify pathogen activity, and antibiotics play an important role in this process.

    “The microbiota can favor or amplify the activity of pathogens, and antibiotics play an important role in this process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In humans, phosphatidylcholine or L-carnitine administration augments TMA plasma levels and increases cardiovascular disease risk; antibiotic treatment dramatically reduces TMA levels.

    “Also in humans, PC or LC administration augmented TMA plasma levels, and increased the risk for cardiovascular disease; notably, antibiotic treatment dramatically reduced TMA levels in these subjects [68, 70].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Koeth RA Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Nature medicine 2013 19 576 585 PMC3650111 23563705 source

      Not checked in the free run.

    • cites [70] Tang WH Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk The New England journal of medicine 2013 368 1575 1584 23614584 PMC3701945 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low fat diet, antibiotic treatment, or pharmacological inhibition of microbial conversion of primary to secondary bile acids has a protective effect in this model.

    “Low fat diet, antibiotic treatment or pharmacological inhibition of microbial conversion of primary to secondary bile acids has had a protective effect in this model.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Yoshimoto S Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome Nature 2013 499 97 101 23803760 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vegan or vegetarian subjects have a reduced or non-existent capacity to produce TMA upon L-carnitine supplementation, proposed to be because their bacteria cannot perform this conversion.

    “Vegan or vegetarian subjects exhibited a reduced or non-existent capacity to produce TMA upon LC supplementation, and it was proposed that bacteria, presumably selected through the host’s diet, were incapable of performing this biochemical conversion [68].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] Koeth RA Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Nature medicine 2013 19 576 585 PMC3650111 23563705 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Upon expansion and DSS-induced epithelial damage, this pathobiont enters the circulation and induces IL1-β production by macrophages, promoting sepsis.

    “Upon expansion and DSS-induced epithelial damage, this pathobiont could enter the circulation and induce IL1-β production by macrophages, thus promoting sepsis [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Ayres JS Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota Nature medicine 2012 18 799 806 PMC3472005 22522562 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NLRP3 activation leads to IL1β production, fostering inflammation and inducing colitis, which can be ameliorated by antibiotic treatment.

    “Consequently, NLRP3 activation leads to production of IL1β, fostering inflammation and inducing colitis which can be ameliorated by antibiotic treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Seo SU Distinct Commensals Induce Interleukin-1beta via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury Immunity 2015 42 744 755 25862092 PMC4408263 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Obese mice harbor an altered microbiota enriched in Clostridia that produces high quantities of DCA, contributing to liver inflammation and predisposing the host to hepatic cancer.

    “Obese mice harbor an altered microbiota enriched in Clostridia that produces high quantities of DCA, contributing to liver inflammation, and predisposing the host to an increased risk of developing hepatic cancer [66].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Yoshimoto S Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome Nature 2013 499 97 101 23803760 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NLRP6-deficient mice harbor a microbiota more prone to induce colitis upon DSS treatment, and this phenotype can be transferred to healthy wild-type mice upon conventionalization.

    “NLRP6-deficient mice harbor a microbiota that is more prone to induce colitis upon DSS treatment, a phenotype that could be transferred to healthy WT mice upon conventionalization [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Elinav E NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis Cell 2011 145 745 757 21565393 PMC3140910 source

      Not checked in the free run.

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

    Premisecitation

    This nitrate-based growth advantage has been proposed as a leading cause of inflammation-related dysbiosis.

    “This has been proposed to be a leading cause of inflammation-related dysbiosis [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Winter SE Host-derived nitrate boosts growth of E. coli in the inflamed gut Science 2013 339 708 711 23393266 PMC4004111 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The persistent antibiotic effects in healthy volunteers include a dramatic loss of diversity and of specific taxa.

    “including a dramatic loss in diversity as well as in representation of specific taxa”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Jernberg C Long-term ecological impacts of antibiotic administration on the human intestinal microbiota The ISME journal 2007 1 56 66 18043614 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C-section-delivered infants have a microbiota resembling adult skin, with Streptococci as a dominant species.

    “the microbiota of C-section delivered infants resembles that populating the skin of adults, with Streptococci being a dominant species [85].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Dominguez-Bello MG Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns Proceedings of the National Academy of Sciences of the United States of America 2010 107 11971 11975 20566857 PMC2900693 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dendritic cell migration is not impaired in germ-free mice and is restored in conventional mice upon antibiotic treatment, implicating the microbiota in promoting scar formation.

    “DC migration was not impaired in GF mice, and was restored in conventional mice upon antibiotic treatment, implicating a role for the microbiota in promoting scar formation [79].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Fonseca DM Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity Cell 2015 163 354 366 26451485 PMC4826740 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At least three major forces drive antibiotic resistance: immune recognition and response, bacterial competition within communities, and exogenous antibiotic pressure.

    “at least 3 major forces drive the development and spread of antibiotic resistance in the host or in the environment: i) immune recognition and response; ii) bacterial competition within communities; iii) exogenous antibiotic pressure [97]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Modi SR Antibiotics and the gut microbiota The Journal of clinical investigation 2014 124 4212 4218 25271726 PMC4191029 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    That early macrolide-associated profile includes induction of antibiotic resistance genes and a decrease in bile salt hydrolases.

    “an induction of ARGs, and a decrease in bile salt hydrolases”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Korpela K Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children Nature communications 2016 7 10410 PMC4737757 26811868 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This immunological scar impairs mucosal immune responses and oral tolerance to food antigens.

    “This “immunological scar” has been found to impair mucosal immune responses as well as oral tolerance to food antigens.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Fonseca DM Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity Cell 2015 163 354 366 26451485 PMC4826740 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    That early macrolide-associated profile positively correlates with later asthma or increased body mass index.

    “Such profile positively correlated with either a later development of asthma, or an increase in body mass index [89].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Korpela K Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children Nature communications 2016 7 10410 PMC4737757 26811868 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An early survey found that a sizable fraction of the anaerobe compartment in healthy subjects is resistant to one or multiple antibiotics, and this proportion increases after antibiotic treatment.

    “An early survey suggested that a sizable fraction of the anaerobe compartment within the microbiota of healthy subjects is resistant to one or multiple antibiotics, with the proportion of such bacteria increasing following antibiotic treatment [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Levy SB High frequency of antimicrobial resistance in human fecal flora Antimicrobial agents and chemotherapy 1988 32 1801 1806 3266729 PMC176022 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The persistent antibiotic effects in healthy volunteers include emergence of antibiotic-resistant strains and upregulation of antibiotic resistance genes.

    “insurgence of antibiotic resistant strains, and up-regulation of antibiotic resistance genes (ARGs) [81]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Jernberg C Long-term ecological impacts of antibiotic administration on the human intestinal microbiota The ISME journal 2007 1 56 66 18043614 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This mechanism yields higher growth rates for the entire population than for isolated resistant clones, which have lower proliferation due to the metabolic cost of mutations.

    “This mechanism resulted in higher growth rates of the entire population when compared to those of isolated resistant clones, which displayed lower proliferative capacity due to the metabolic cost of acquired mutations [108].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Lee HH Bacterial charity work leads to population-wide resistance Nature 2010 467 82 85 20811456 PMC2936489 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The bacterial gene lpxF encodes a phosphatase that reduces LPS negative charge and impairs polymyxin B binding.

    “the bacterial gene lpxF, which encodes a phosphatase acting on LPS to diminish its negative charge and consequently, impair polymyxin B ligation to the bacterium [99].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Cullen TW Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation Science 2015 347 170 175 25574022 PMC4388331 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Because Bsa and vancomycin share a cell-wall target, strain Y acquires vancomycin resistance and greater virulence in infected mice.

    “as Bsa and vancomycin bind to a common target within the cell wall, the Y strain acquires resistance to the antibiotic, resulting in greater virulence in infected mice [100].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] Koch G Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition Cell 2014 158 1060 1071 25171407 PMC4163622 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Acquisition of antibiotic resistance modifies ecological interactions within a homogeneous bacterial community and contributes to community well-being.

    “This study highlighted how acquisition of antibiotic resistance modifies ecological interactions within a homogeneous bacterial community, contributing to its own well-being.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Lee HH Bacterial charity work leads to population-wide resistance Nature 2010 467 82 85 20811456 PMC2936489 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Twins have greater resistome similarity to each other than to unrelated infants or their mothers, suggesting vertical transmission is not crucial to resistome establishment.

    “twins display remarkably greater resistome similarity to each other than to unrelated infants or their mothers, suggesting that vertical transmission does not play a crucial role in its establishment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [105] Moore AM Gut resistome development in healthy twin pairs in the first year of life Microbiome 2015 3 27 26113976 PMC4480905 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pigs fed a growth-enhancing antibiotic cocktail for two weeks show increased ARG expression, including tolerance to drugs not administered.

    “pigs were fed a diet supplemented with a growth-enhancing antibiotic cocktail for two weeks. Subsequently, their microbiota showed increased expression of ARGs, conferring tolerance even to drugs that were not administered during the study [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Looft T In-feed antibiotic effects on the swine intestinal microbiome Proceedings of the National Academy of Sciences of the United States of America 2012 109 1691 1696 22307632 PMC3277147 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Antibiotic resistance is naturally present in bacterial communities including the gut microbiota, where it can be induced by several driving forces.

    “these data provide evidence that antibiotic-resistance is naturally present in bacterial communities, including the gut microbiota, where it can be induced by several driving forces.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Bacterial resistance can be induced and maintained by the immune response.

    “suggesting that bacterial resistance can be both induced and maintained by the immune response [99].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Cullen TW Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation Science 2015 347 170 175 25574022 PMC4388331 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The resistome expands over time, with the number of ARGs in the human microbiome positively correlating with age.

    “the resistome expands over time, as the number of ARGs within the human microbiome positively correlate with age [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Lu N DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related Scientific reports 2014 4 4302 24618772 PMC3950639 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Some of these soil bacterial resistance cassettes are flanked by transposable elements, suggesting horizontal gene transfer between soil and pathogenic bacteria.

    “Some cassettes were flanked by transposable elements, strongly suggesting horizontal gene transfer between soil-resident and pathogenic bacteria [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Forsberg KJ The shared antibiotic resistome of soil bacteria and human pathogens Science 2012 337 1107 1111 22936781 PMC4070369 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In that model, pPD1 transfers to commensal bacteria, raising the possibility of conjugation to VRE and suggesting caution for clinical use.

    “in this model, transfer of the plasmid to commensal bacteria was also observed, raising the possibility of pPD1 conjugation to VRE itself, and therefore, suggesting that caution should be taken with the clinical application of this approach.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Kommineni S Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract Nature 2015 526 719 722 26479034 PMC4978352 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The clindamycin resistance transfer factor gene BtgA has the highest number of SNPs within 200 human gut metagenomes, with other conjugal transfer factors following.

    “clindamycin resistance transfer factor gene (BtgA) has been identified as carrying the highest number of SNPs within 200 human gut metagenomes, and other conjugal transfer factors have followed in this ranking [112].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Schloissnig S Genomic variation landscape of the human gut microbiome Nature 2013 493 45 50 23222524 PMC3536929 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VRE colonizes the intestine after antibiotic treatment before spreading to the bloodstream and is a major threat for hospitalized patients.

    “VRE colonizes the intestine following antibiotic treatment, prior to spreading to the bloodstream, and thus, represents a major threat for hospitalized patients [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Ubeda C Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans The Journal of clinical investigation 2010 120 4332 4341 21099116 PMC2993598 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Antibiotic resistance regulates microbial interactions and shapes microbial communities, possibly playing a prominent role in gut microbiota ecology.

    “Thus, antibiotic resistance plays a strong role in regulating microbial interactions and shaping microbial communities, possibly representing a prominent factor in the ecological regulation of the gut microbiota.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Competence genes located in this region are upregulated by these drugs, promoting a state of competence.

    “Genes encoding for competence functions are located in this region, and consequently, they are upregulated in the presence of these drugs, promoting a state of competence.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [115] Slager J Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin Cell 2014 157 395 406 24725406 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Horizontal gene transfer can occur among commensals, environmental bacteria, or between the two.

    “HGT can take place among commensals, environmental bacteria or, importantly, between the two.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Hehemann JH Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota Nature 2010 464 908 912 20376150 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Improving sanitation, expanding vaccine use, and strengthening hospital infection control are effective tools for reducing the need for antibiotic therapies.

    “improving sanitation, expanding the use of vaccines, and strengthening hospital infection control have proven extremely effective tools in reducing the needs for antibiotic therapies.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Laxminarayan R Antibiotic effectiveness: balancing conservation against innovation Science 2014 345 1299 1301 25214620 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The SXT element has emerged commonly in V. cholerae isolates from patients in recent decades, potentially due to antibiotic-induced resistance transfer.

    “in recent decades, the SXT element has emerged, presenting itself quite commonly in V. cholerae isolates from patients, potentially a result of antibiotic-induced resistance transfer [113].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Beaber JW SOS response promotes horizontal dissemination of antibiotic resistance genes Nature 2004 427 72 74 14688795 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lactocillin, a thiopeptide from L. gasseri bgc66, inhibits S. aureus and G. vaginalis but not commensals.

    “Lactocillin, a thiopeptide encoded by one such cluster (i.e. bgc66 from L. gasseri), has been produced and characterized, showing strong inhibitory activity against common pathogens such as S. aureus and G. vaginalis, but not against commensals [122].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Donia MS A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics Cell 2014 158 1402 1414 25215495 PMC4164201 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Transformation, conjugation, and transduction are all implicated in transfer of antibiotic resistance genes.

    “All three mechanisms have been implicated in transfer of antibiotic resistance genes (Figure 3) [97, 110].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [97] Modi SR Antibiotics and the gut microbiota The Journal of clinical investigation 2014 124 4212 4218 25271726 PMC4191029 source

      Not checked in the free run.

    • cites [110] Costello EK The application of ecological theory toward an understanding of the human microbiome Science 2012 336 1255 1262 22674335 PMC4208626 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ecological modeling shows that when each bacterial strain protects only itself from a competitor-produced antibiotic, community fluctuations increase and one strain ultimately dominates.

    “ecological modeling has shown that in a bacterial consortium where every bacterial strain protects only itself from the action of a given antibiotic produced by a competing species (“rock, paper, scissors” model), fluctuations in the composition of the consortium increase, giving rise to a very unstable community that is ultimately dominated by one strain.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Kelsic ED Counteraction of antibiotic production and degradation stabilizes microbial communities Nature 2015 521 516 519 25992546 PMC4551410 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because Japanese diets are rich in seaweed porphyran, this finding implicates horizontal gene transfer between environmental and gut commensal bacteria.

    “As Japanese diets are highly enriched in seaweed containing porphyran, this work strongly implicated horizontal gene transfer between environmental and gut commensal bacterial species.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Hehemann JH Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota Nature 2010 464 908 912 20376150 source

      Not checked in the free run.

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

    Premisecitation

    Leaky protection conferred by an antibiotic-degrading species to surrounding bacteria is proposed to be of public benefit.

    “it has been proposed that leaky protection conferred by an antibiotic-degrading species to other surrounding bacteria is of public benefit [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Kelsic ED Counteraction of antibiotic production and degradation stabilizes microbial communities Nature 2015 521 516 519 25992546 PMC4551410 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    ARGs spread among bacteria through conjugation, transduction, and transformation, and antibiotic exposure promotes this process.

    “Thus, ARGs spread among bacteria through conjugation, transduction and transformation, and this process is promoted by antibiotic exposure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Ribocil binding inhibits translation of the ribB transcript in E. coli, causing cell death by riboflavin starvation.

    “Ribocil binding inhibits translation of ribB transcript in E. coli, inducing cell death by riboflavin starvation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [123] Howe JA Selective small-molecule inhibition of an RNA structural element Nature 2015 526 672 677 26416753 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    No resistance developed against the phagemids, and the system allowed discrimination of single polymorphic nucleotides.

    “no resistance developed against the phagemids, and the sensitivity of the system allowed discrimination of single polymorphic nucleotides.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [127] Bikard D Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials Nature biotechnology 2014 32 1146 1150 PMC4317352 25282355 source

      Not checked in the free run.

    • cites [128] Citorik RJ Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases Nature biotechnology 2014 32 1141 1145 PMC4237163 25240928 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Avidocin-CDs selectively targets C. difficile strain BI/NAP1/027 and promotes pathogen clearance in mice after oral administration.

    “the bacteriocin Avidocin-CDs, engineered to selectively target the clinically relevant C. difficile strain BI/NAP1/027, has been reported to promote pathogen clearance in mice upon oral administration.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [125] Gebhart D A modified R-type bacteriocin specifically targeting Clostridium difficile prevents colonization of mice without affecting gut microbiota diversity mBio 2015 6 PMC4453579 25805733 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Thuricin-CD is as effective as vancomycin or metronidazole against C. difficile without impacting microbiota composition in a fecal-culture colon model.

    “Thuricin-CD, a bacteriocin produced by Bacillus thuringiensis, has been shown to be as effective as vancomycin or metronidazole against C. difficile without impacting microbiota composition in a fecal-culture system that models human colon [124].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [124] Rea MC Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon Proceedings of the National Academy of Sciences of the United States of America 2011 108 Suppl 1 4639 4644 20616009 PMC3063588 source

      Not checked in the free run.

85 of 85

  • The paper relies on this without support.

    Findings from mouse models of microbiota-immune interactions and disease can be generalized to human physiology and disease.

    “Collectively, these murine studies show that commensal bacteria contribute to the maintenance of immune tolerance in the host, principally through induction of regulatory T cells.”

  • The paper relies on this without support.

    The human intestine is densely colonized with a wide variety of microbes.

    “As the human intestine is densely colonized with an amazing variety of microbes”
2 of 2

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?

  • Intake of antibiotics profoundly affects the composition and function of the gut microbiota and may introduce long-lasting adverse effects on the host.

    “Intake of antibiotics profoundly affects the composition and function of the gut microbiota, and may introduce long-lasting adverse effects on the host.129”

    From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [129]

  • Species richness and biodiversity were not fully recovered at six months, indicating long-lasting loss of unique bacterial species.

    “Notably, species richness and biodiversity were not fully recovered at six months, indicating long-lasting loss of unique bacterial species, consistent with previous studies (Becattini et al., 2016; Dethlefsen and Relman, 2011; Modi et al., 2014).”

    From Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans (2019) · cites this paper as Becattini et al., 2016

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 rodentium pathogen is assigned two genera

    Minor

    The body calls the pathogen *Clostridium rodentium*, while a cited reference names it *Citrobacter rodentium*. The paper therefore gives conflicting genus names for the rodentium infection discussed in mice.

1 of 1

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Authors
Becattini, S., Taur, Y., & Pamer, E. G.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Pamer, Eric G.
ORCID
Venue
Trends in Molecular Medicine
Publisher
Elsevier BV
Published
2016-06
Volume
22
Issue
6
Pages
458-478
ISSN
1471-4914 (ISSN-L)
DOI
10.1016/j.molmed.2016.04.003
PMC
PMC4885777
OpenAlex
W2381299150
Semantic Scholar
91637ceb5682b9b8cc4e5efc7e20535abee2ea75
Cited by
901
References
152
Citations by year
2026: 61 · 2025: 105 · 2024: 78 · 2023: 106 · 2022: 110 · 2021: 138 · 2020: 114 · 2019: 82 · 2018: 50 · 2017: 46 · 2016: 11
FWCI
5.72
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Molecular Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • National Institutes of Health (5k23ai095398-05)
  • National Cancer Institute (P01CA023766, P30CA008748)
  • National Institute of Allergy and Infectious Diseases (R01AI039031, R01AI095706, K23-AI095398, U01AI124275, R01AI042135)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Keywords
gut microbiota, antibiotics, antibiotic-induced dysbiosis, commensal bacteria, multidrug resistance, antimicrobial resistance, host-microbiota interactions, disease susceptibility
MeSH terms
Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Bacteria, Cell Line, Humans, Immune System, Drug Resistance, Bacterial, Mice

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 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

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

What counts as a claim ›How we measure confidence ›How we check this ›

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