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Cited by 320Gastrointestinal motility and disordersGut microbiota and healthProbiotics and Fermented Foods

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

Open access
Distrutti, Eleonora, Monaldi, Lorenzo, Ricci, Patrizia, Fiorucci, Stefano·2016·World Journal of Gastroenterology
DOI 10.3748/wjg.v22.i7.2219PMC PMC4734998
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Abstract

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that disturbed gut microbiota contributes to irritable bowel syndrome (IBS) and that microbiota manipulation is a promising therapeutic strategy. Probiotics have the most supportive evidence, while prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation require further randomized controlled trials.

Key findings

  • IBS affects 10%-15% of the general population, and most data support altered luminal and mucosal microbiota in IBS subgroups versus healthy individuals, including decreased Lactobacilli and Bifidobacteria, increased aerobes, and higher mucosal bacteria; a high Firmicutes:Bacteroidetes ratio is found in some IBS patients and appears to correlate with depression and anxiety.
  • Probiotics show the strongest evidence: Moayyedi et al examined 18 RCTs including 1650 IBS patients and found probiotics significantly better than placebo for overall symptoms, with significant improvement in pain, flatulence, and bloating but not urgency; Hungin et al selected 19 studies including 1807 patients and reported responder rates of 18%-80% in IBS versus 5%-50% in healthy controls, with a favorable safety profile.
  • Didari et al meta-analyzed 15 trials including 882 patients with D-IBS, C-IBS, and A-IBS and found probiotics more effective than placebo in reducing abdominal pain after 8 and 10 wk, with a higher effect at week 8; Table 2 grades evidence as high for global symptom relief and abdominal pain, moderate for bloating/distension, bowel habit, and quality of life, low for constipation and flatus, and very low for diarrhea.
  • Rifaximin evidence comes from TARGET 1 and TARGET 2, which included 1260 patients with IBS without constipation: adequate relief of global IBS symptoms was 40.7% vs 31.7% for rifaximin vs placebo, and adequate relief of bloating, abdominal pain, and stool consistency was 40.2% vs 30.2%; FMT data are limited, with Borody et al reporting approximately 50% symptom relief in an early case series and Pinn et al reporting 70% resolution or improvement in refractory IBS patients.

Methods

  • Narrative review; no primary data are presented.
  • The paper synthesizes human microbiota studies in IBS and therapeutic trials, including meta-analyses and RCTs; for probiotics, it focuses on meta-analyses and extensive reviews published in the last 5 years that screened RCTs in IBS patients.
  • Main analysis is qualitative synthesis of microbiota alterations and therapeutic evidence; no formal systematic search strategy or quantitative pooling is described.

Limitations

  • The paper states that probiotic trials are highly heterogeneous, often have inadequate sample size, poor study design, and use various probiotic strains; meta-analyses recommend additional RCTs with appropriate endpoints and design.
  • It states that prebiotic results are conflicting and may exacerbate IBS symptoms, synbiotic experience is limited with poor-quality studies, FMT data on IBS are scanty and randomized placebo-controlled studies are required, and rifaximin is effective in less than 50% of patients, has been studied mainly in non-constipated IBS, and has unknown long-term and microbiota effects.
  • Evident from the text: as a narrative review, it does not report a systematic search, formal risk-of-bias assessment, or quantitative synthesis for most therapeutic sections.

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

Integrity signals

Registry

Crossref · 10.3748/wjg.v22.i7.2219

Cites

318 of 318 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 186 cited sources checked · 0 supported · 0 flagged

  • Findingcitation
    § Perturbation in microbiota composition

    A higher degree of temporal instability of the microbiota among IBS patients has been detected.

    “Furthermore, a higher degree of temporal instability of the microbiota among IBS patients has been detected.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3963]

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  • Findingcitation
    § Perturbation in microbiota composition

    Mucosal bacteria are more abundant in IBS patients than in healthy controls.

    “Finally mucosal bacteria have also been found to be more abundant in IBS patients than in healthy controls (Table 1).”
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    • cites [3963]

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  • Findingcitation
    § Perturbation in microbiota composition

    Approximately 10% of IBS patients report that their symptoms began following an episode of infectious diarrhea (post-infectious IBS).

    “Second, it has been reported that approximately 10% of IBS patients refer that their symptoms began following an episode of infectious diarrhea [7577] , the so-called post infectious IBS (PI-IBS), a condition with a clear infective trigger that may alter the normal intestinal microbiota.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7577]

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  • Findingcitation
    § Probiotics

    Probiotic administration was significantly better than placebo at improving overall IBS symptoms.

    “Indeed, probiotic administration was significantly better than placebo at improving overall symptoms.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [142] source

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  • Findingnone given
    § Luminal metabolism

    Studies that have examined the effect of probiotics supplementation on fecal SCFAs in humans have provided conflicting results.

    “studies that have examined the effect of probiotics supplementation on fecal SCFAs in humans have provided conflicting results”
    Quote in the paperNot a substantial claim
  • May combine two claims. 31
  • Classified as probably not a substantial claim. 9
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingcitation
    § Perturbation in microbiota composition

    In IBS patients compared with healthy subjects, microbial diversity is reduced, the proportion of specific bacterial groups is altered, and the degree of variability in microbiota composition is different.

    “Using culture-based techniques and a 16S rRNA gene-based phylogenetic microarray analysis, it has been demonstrated that the diversity of microbial population is reduced, the proportion of specific bacterial groups is altered and the degree of variability in the microbiota composition is different in IBS patients when compared with healthy subjects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3963]

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    Findingcitation
    § Perturbation in microbiota composition

    IBS patients have decreased amounts of Lactobacilli and Bifidobacteria and increased amounts of aerobes relative to anaerobes.

    “Examples of these modifications are a decreased amount of Lactobacilli and Bifidobacteria along with an increased amount of aerobes relatively to anaerobes in IBS patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3963]

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    Findingcitation
    § Probiotics

    Probiotics had a favorable safety profile with no difference in adverse events among the 23 specific probiotic treatments and placebo.

    “Probiotics had a favorable safety profile with no difference in adverse events among the 23 specific probiotic treatments and placebo [173] .”
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    • cites [173] source

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  • May combine two claims.

    Findingcitation
    § Probiotics

    Probiotics showed a statistically significant effect in improving individual IBS symptoms such as pain, flatulence and bloating, but not urgency.

    “Moreover probiotics showed a statistically significant effect in improving individual symptoms such as pain, flatulence and bloating, but not urgency.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [142] source

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

    Findingnone given
    § Luminal metabolism

    Studies demonstrating a strong correlation between the assumption of probiotics and the level of fecal SCFAs in IBS patients are lacking.

    “studies demonstrating a strong correlation between the assumption of probiotics and the level of fecal SCFAs in IBS patients are lacking”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning
    § PREBIOTICS

    Few studies have evaluated the efficacy of prebiotics in IBS and existing results are conflicting.

    “However, few studies have evaluated the efficacy of prebiotics in IBS and existing results are conflicting.”
    Quote in the paperNot a substantial claim

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

    Findingnone given
    § ANTIBIOTICS

    The effect of rifaximin on gut microbiota composition is essentially unknown.

    “the effect of rifaximin on gut microbiota composition is essentially unknown”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning
    § FECAL TRANSPLANTATION IN IBS: A NEW LIFE FOR AN OLD TREATMENT?

    Only anecdotal data have been reported about the efficacy of FMT for IBS treatment, and results are far from conclusive.

    “To date, only anecdotal data have been reported about the efficacy of FMT for IBS treatment, results being far conclusive.”
    Quote in the paperSubstantial claim

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

    Findingnone given
    § CONCLUSION

    All metaanalysis point out the weakness of the majority of the studies and recommend additional RCT trials to confirm the positive findings reported by small studies.

    “all metaanalysis point out to the weakness of the majority of the studies and recommend additional RCT trials to confirm the positive findings reported by small studies”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning
    § Abstract

    Probiotics appear an attractive option for IBS in terms of both efficacy and safety.

    “In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Perturbation in microbiota composition

    There is increasing evidence of activation of the intestinal immune system in IBS leading to micro-inflammation, with increased mucosal intraepithelial lymphocytes, mast cells and 5-hydroxytryptamine-secreting enterochromaffin cells.

    “First, there is increasing evidence of an activation of the intestinal immune system in IBS leading in a micro-inflammation, with studies demonstrating increased concentrations of mucosal intraepithelial lymphocytes [65,66] , mast cells [6669] and 5hydroxytryptaminesecreting enterochromaffin cells [65] .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [65] source

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    • cites [66] source

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  • Classified as probably not a substantial claim.

    Premisecitation
    § Perturbation in microbiota composition

    The Rome Team Working Group concluded there is good evidence supporting that the intestinal microbiota is perturbed in patients with IBS.

    “Consistent with this view, the clinical guidance regarding the modulation of intestinal microbiota in IBS provided by the Rome Team Working Group has recently concluded that there is good evidence supporting the concept that the intestinal microbiota is perturbed in patients with IBS [64] .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] source

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  • May combine two claims. The quote only partly states this claim.

    Interpretationreasoning
    § Microbiota and colo-intestinal motility

    In IBS, altered composition and/or activity of microbiota may disrupt microbiota-gut-brain communication, leading to immune activation, production of proinflammatory cytokines, production of SCFAs toxic at high concentration, HPA axis activation, and altered intestinal motility and sensation.

    “In irritable bowel syndrome (IBS), the altered composition and/or activity of microbiota may induce a disruption of this communication leading to activation of immune system and production of proinflammatory cytokines”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Mechanisms by which gut microbiota modulates motility, visceral sensitivity, and neuroimmune signaling in animal models also operate in human IBS.

  • May combine two claims.

    Interpretationcitation
    § Microbiota and colo-intestinal motility

    Gut microbiota modulates gut motor function, which in turn can alter intestinal microbiota composition.

    “Nonetheless gut microbiota modulates gut motor function, which in turn can alter the intestinal microbiota composition.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [93] Caenepeel P, Janssens J, Vantrappen G, Eyssen H, Coremans G. Interdigestive myoelectric complex in germ-free rats. Dig Dis Sci 1989;34:1180-1184. source

      Not checked in the free run.

    • cites [94] source

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    • cites [95] Husebye E, Hellström PM, Midtvedt T. Intestinal microflora stimulates myoelectric activity of rat small intestine by promoting cyclic initiation and aboral propagation of migrating myoelectric complex. Dig Dis Sci 1994;39:946-956. source

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    • cites [96] Husebye E, Hellström PM, Sundler F, Chen J, Midtvedt T. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am J Physiol Gastrointest Liver Physiol 2001;280:G368-G380. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Composition of intestinal microbiota in IBS

    Probiotics might reshape the intestinal ecosystem, generating an ecological milieu unfavorable for the growth of harmful species by increasing the number of Lactobacilli and Bifidobacteria that stabilize the intestinal microbiota.

    “However, it has been suggested that probiotics might reshape the intestinal ecosystem generating an ecological milieu that is unfavorable for the growth of harmful species by increasing the number of Lactobacilli and Bifidobacteria [199] that will stabilize the intestinal microbiota [174,179] .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [199] source

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    • cites [174] source

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    • cites [179] source

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    • Rests on an assumption: The clinical benefits of probiotics in IBS are mediated by their effects on gut microbiota composition or function.

  • May combine two claims.

    Premisecitation
    § Epithelial barrier/intestinal inflammation/immune activation

    Saccharomyces boulardii supplementation increased the tissue IL-10/IL-12 ratio and ameliorated the quality of life of D-IBS.

    “as well as an increase in the tissue IL-10/IL-12 ratio ameliorating the quality of life of DIBS [232]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [232] source

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    Premisecitation
    § Epithelial barrier/intestinal inflammation/immune activation

    Saccharomyces boulardii supplementation induced a significant decrease in blood and tissue levels of proinflammatory cytokines IL8 and TNFa and an increase in antiinflammatory IL-10 levels.

    “Saccharomyces boulardii supplementation induced a significant decrease in blood and tissue levels of proinflammatory cytokines IL8 and TNFa and an increase in antiinflammatory IL-10 levels”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [232] source

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

    Premisecitation
    § Luminal metabolism

    Bifidobacterium lactis Bb12 increased the fecal level of acetate and lactate in preterm infants.

    “the Bifidobacterium lactis Bb12 increased the fecal level of acetate and lactate in preterm infants [243]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [243] source

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    Premisecitation
    § Luminal metabolism

    Acetic and propionic acid-producing bacteria lead to enhanced production of SCFAs that are toxic at high concentrations and stimulate 5-HT release from intestinal nerve endings.

    “leading to en hanced production of SCFAs that are toxic at high concentrations and stimulate 5-HT release from the intestinal nerve endings [239]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [239] source

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    Premisecitation
    § Dysfunction of the brain-gut axis and psychological distress

    Bifidobacterium animalis subsp lactis BB12 and Propionibacterium jensenii 702 improved the immune environment of stressed animals and protected against stress-induced disturbances in adult gut microflora.

    “but also improved the immune environment of stressed animals and protected against stress induced disturbances in adult gut microflora [246]”
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    • cites [246] source

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    Premisecitation
    § Luminal metabolism

    Bifidobacteria-fermented milk increased fecal butyrate, propionate and short-chain fatty acid concentrations but ameliorated symptoms in patients affected by UC.

    “bifidobacteriafermented milk increased fecal butyrate, propionate and short-chain fatty acid concentrations but ameliorated symptoms in patients affects by UC [242]”
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    • cites [242] source

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    Premisecitation
    § Dysfunction of the brain-gut axis and psychological distress

    Bifidobacterium animalis subsp lactis BB12 and Propionibacterium jensenii 702 induced activation of neonatal stress pathways and an imbalance in gut microflora.

    “Bifidobacterium animalis subsp lactis BB12 ® and Propionibacterium jensenii 702 induced activation of neonatal stress pathways and an imbalance in gut microflora”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [246] source

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    Premisecitation
    § Dysfunction of the brain-gut axis and psychological distress

    The gut microbiota modulates the CNS via the ENS, the ANS, the HPA axis and vice versa.

    “There are evidence that the gut microbiota modulates the CNS via the ENS, the ANS, the HPA axis and vice versa [124,213]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [124] source

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    Interpretationreasoning
    § Dysfunction of the brain-gut axis and psychological distress

    Intestinal dysbiosis may lead to alteration of the brain-gut axis and probiotics may restore the normal interaction among all components of this pathway.

    “An intestinal dysbiosis may lead to alteration of brain-gut axis and probiotics may restore the normal interaction among all components of this pathway.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § PREBIOTICS

    Long-chain polyunsaturated fatty acids have been tested as active prebiotics.

    “long-chain polyunsaturated fatty acids have been tested as active prebiotics [254]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Interpretationreasoning
    § PREBIOTICS

    Clinical response to prebiotics may be dependent on the prebiotic type and dose, with low doses ineffective and high doses stimulating colonic gas production.

    “The clinical response may be dependent on the prebiotic type and dose, taking into account that low doses may be ineffective and high doses may stimulate colonic gas production.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § PREBIOTICS

    Lactulose and bran, successfully used for constipation, tend to produce substantial amounts of gas and abdominal pain and may aggravate symptoms of IBS.

    “lactulose and bran, that are successfully used for constipation, tend to produce substantial amounts of gas and abdominal pain and may aggravate symptoms of IBS [269271]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [269271]

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    Premisecitation
    § PREBIOTICS

    GOS lowered flatulence and bloating while also improving the anxiety score in IBS.

    “GOS lowering flatulence and bloating while also improving the anxiety score [83]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2009;29:508-518. source

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  • May combine two claims.

    Premisecitation
    § PREBIOTICS

    Fructose and sorbitol mixtures produce a modest increase in stool weight but often increase flatulence and bloating in both healthy volunteers and IBS patients.

    “fructose and sorbitol mixtures produce a modest increase in stool weight, they often increase flatulence and bloating in both healthy volunteers and IBS patients [272,273]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [272] Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology 1990;99:1016-1020. source

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    • cites [273] Symons P, Jones MP, Kellow JE. Symptom provocation in irritable bowel syndrome. Effects of differing doses of fructose-sorbitol. Scand J Gastroenterol 1992;27:940-944. source

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  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § SYNBIOTICS

    Limited experience and the poor quality of published studies do not allow any recommendation on synbiotic use in IBS.

    “the limited experience and the poor quality of published studies do not allow any recommendation on their use in IBS”
    Quote in the paperSubstantial claim

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    Premisecitation
    § SYNBIOTICS

    Few open label trials and PCT studies have evaluated the efficacy of synbiotics in both functional pain and IBS, all demonstrating a superiority of probiotic/prebiotic combinations vs placebo.

    “Few open label trials [64,279] and PCT studies have evaluated the efficacy of synbiotics in both functional pain [280] and IBS, all demonstrating a superiority of the probiotic/prebiotic combinations vs placebo [281283]”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [64] source

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    • cites [279] Saneian H, Pourmoghaddas Z, Roohafza H, Gholamrezaei A. Synbiotic containing Bacillus coagulans and fructo-oligosaccharides for functional abdominal pain in children. Gastroenterol Hepatol Bed Bench 2015;8:56-65.

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    • cites [280] source

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    • cites [281283]

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    Premisecitation
    § ANTIBIOTICS

    These broad-spectrum antibiotics are absorbable, causing local and systemic side effects.

    “however, these drugs are absorbable causing local and systemic side effects”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [287] source

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    • cites [288] source

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    Premisecitation
    § ANTIBIOTICS

    A pooled analysis by Schoenfeld et al confirmed the safety and tolerability profile of rifaximin in comparison with placebo, with similar incidence of drug-related adverse events.

    “a pooled analysis by Schoenfeld et al [292] has confirmed the safety and tolerability profile of rifaximin in comparison with placebo, with similar incidence of drug-related adverse events”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [292] source

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  • May combine two claims.

    Interpretationcitation
    § ANTIBIOTICS

    Rifaximin has virtually no systemic absorption, is effective in improving IBS symptoms with a low bacterial resistance profile and has a favorable side-effects profile.

    “rifaximin has virtually no systemic absorption, is effective in improving IBS symptoms with low bacterial resistance profile and has a favorable sideeffects profile”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § FECAL TRANSPLANTATION IN IBS: A NEW LIFE FOR AN OLD TREATMENT?

    A large case series of CDI patients has showed rapid response and a cure rate of nearly 90%, without significant adverse event rate.

    “a large case series of CDI patients has showed rapid response and a cure rate of nearly 90%, without significant adverse event rate [295]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [295] source

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  • May combine two claims.

    Premisecitation
    § FECAL TRANSPLANTATION IN IBS: A NEW LIFE FOR AN OLD TREATMENT?

    The first case series on FMT in IBS also included IBD and CDI patients and did not show any distinction within the results between these different diseases.

    “however, the study also included IBD and CDI patients and did not show any distinction within the results between these different diseases”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [305] Borody TJ, George L, Andrews P, Brandl S, Noonan S, Cole P, Hyland L, Morgan A, Maysey J, Moore-Jones D. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med J Aust 1989;150:604. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given
    § CONCLUSION

    To date, probiotic supplementation and antimicrobial therapy with not absorbable antibiotics are promising treatment for IBS.

    “to date, probiotic supplementation and antimicrobial therapy with not absorbable antibiotics are promising treatment”
    Quote in the paperSubstantial claim

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

    Interpretationnone given
    § CONCLUSION

    FMT might be a reasonable option for treating IBS, as it is an inexpensive and easy treatment.

    “FMT might be a reasonable option for treating IBS, as it is an inexpensive and easy treatment”
    Quote in the paperNot a substantial claim
38 of 38

  • The paper relies on this without support.

    Mechanisms by which gut microbiota modulates motility, visceral sensitivity, and neuroimmune signaling in animal models also operate in human IBS.

    “antibiotics-induced intestinal dysbiosis mo dified colonic painrelated and motor responses by upregulation of TLR4 and TLR7 and downregulation of the antinociceptive cannabinoid 1 and mu-opioid receptor in mice [115] .”

  • The paper relies on this without support.

    The clinical benefits of probiotics in IBS are mediated by their effects on gut microbiota composition or function.

    “probiotics have been shown effective in modulating several mechanisms that might have a mechanistic role in IBS pathogenesis, including effects on composition of intestinal microbiota”

  • The paper relies on this without support.

    Heterogeneous probiotic trials can be pooled to support a general conclusion that probiotics are efficacious in IBS.

    “although a number of metaanalysis or systemic reviews indicate that probiotics may be helpful in the treatment of IBS symptoms, their conclusions vary because of inadequate sample size, poor study design and use of various probiotic strains in the reviewed studies.”

  • The authors state this as an assumption.

    IBS is characterized by impaired intestinal motor functions and by gas retention.

    “From almost 4 decades, the assumption that IBS is characterized by impaired intestinal motor functions [205207] and by gas retention [208] has driven the treatment of IBS to small bowel and colonic dys motilities.”

  • The paper relies on this without support.

    Persistence of IBS-like symptoms occurs in a small percentage of patients after a documented episode of intestinal bacterial or viral infection.

    “it is widely accepted that persistence of IBS-like symptoms occurs in a small percentage of patients after a documented episode of intestinal bacterial or viral infection”

  • The paper relies on this without support.

    IBS is characterized by increased intestinal permeability, a biomarker of impaired epithelial barrier function.

    “animal and epidemiological studies indicate that IBS is characterized by an increased intestinal permeability, a biomarker of impaired epithelial barrier function”

  • The paper relies on this without support.

    Probiotics have a short lifespan within the gut and need repeated doses to keep a constant level.

    “An important safety feature of probiotics is that they have a short lifespan within the gut and need repeated doses to keep a constant level.”

  • The paper relies on this without support.

    Alteration in the gut microbiota composition is a relevant pathogenetic factor in IBS.

    “The alteration in the gut microbiota composition is increasingly considered to be a relevant pathogenetic factor in IBS, leading to the use of antibiotics as a treatment for this multifactorial syndrome.”

  • The paper relies on this without support.

    Small intestinal bacterial overgrowth may be relevant to at least a subset of IBS patients.

    “a SIBO may be relevant to at least a subset of IBS patients, thus justifying an antimicrobial approach”
9 of 9

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?

  • Long-term PPI use facilitates the induction of enteric infection, and, through secondary changes in microbiota composition, these drugs may influence gut-brain axis functions, prompting IBS onset.

    “As previously stated, the long-term PPI use facilitates the induction of enteric infection, and, through secondary changes in microbiota composition, these drugs may influence gut–brain axis functions, prompting IBS onset[117,118].”

    From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [117]

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

    “Patients with IBS with constipation also exhibit a higher proportion of Clostridium, Escherichia coli, Salmonella, Shigella, and Pseudomonas in the gut microbiota [13].”

    From Chronic constipation and gut microbiota: current research insights and therapeutic implications (2024) · cites this paper as [13]

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. 10.1136/gut.45.2008.ii43 · DOI · Paper page
  2. 10.1111/j.1365-2982.2009.01447 · DOI
  3. 10.1111/j.1365-2982.2011.01783 · DOI
  4. 10.7326/0003-4819-145-8200610170-00004 · DOI

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Authors
Distrutti, E., Monaldi, L., Ricci, P., & Fiorucci, S.
Affiliations
University of Perugia (IT)
Corresponding author
Distrutti, Eleonora
ORCID
Venue
World Journal of Gastroenterology
Publisher
Baishideng Publishing Group Inc.
Published
2016-02-21
Volume
22
Issue
7
Pages
2219-2241
ISSN
1007-9327 (ISSN-L)
DOI
10.3748/wjg.v22.i7.2219
PMC
PMC4734998
OpenAlex
W2275770700
Semantic Scholar
0efe65174da858617b153324292cf2bd638fa446
Cited by
320
References
318
Citations by year
2026: 7 · 2025: 19 · 2024: 14 · 2023: 29 · 2022: 37 · 2021: 48 · 2020: 40 · 2019: 46 · 2018: 35 · 2017: 30 · 2016: 15
FWCI
7.14
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Gastroenterology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
gut microbiota, irritable bowel syndrome, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, lactobacilli, Bifidobacterium, dysbiosis, antibiotic therapy, treatment options
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Anti-Bacterial Agents, Bacteria, Humans, Intestines, Treatment Outcome, Probiotics, Irritable Bowel Syndrome, Host-Pathogen Interactions, Prebiotics, Synbiotics

About these checks

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

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

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

Statistics and arithmetic are recomputed, not judged.

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

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

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