Source: IBS Days 2026 abstract book.

 

On behalf of IBS Days 2026 conference, we have interviewed Prof. Carmelo Scarpignato on evidence-based approaches for gut microbiota modulation in IBS. Prof. Carmelo Scarpignato is a clinical pharmacologist and gastroenterologist, teaching at different European Universities. His main scientific interests are pathophysiology and therapy of digestive diseases, microbiota-directed therapies, nutraceuticals, and GI-targeted medical devices.

 

What is the rationale supporting the role of gut microbiome in IBS pathophysiology?

Accumulating evidence indicates that alterations of the gut microbiome are not merely associated with IBS but contribute to symptom generation in a substantial proportion of patients. Compared with healthy individuals, patients with IBS often exhibit a state of dysbiosis characterized by reduced microbial diversity, depletion of beneficial commensal bacteria, and enrichment of potentially pathogenic taxa. These changes may influence gastrointestinal function through multiple mechanisms, including modulation of intestinal permeability, activation of mucosal immune responses, alteration of bile acid metabolism, and production of bioactive metabolites that affect gut motility and visceral sensitivity. Dysbiosis has also been implicated in disturbances of the bidirectional gut–brain axis, thereby contributing to symptom generation and persistence1,2,3.

“An altered gut microbiome may contribute to symptom development in at least a proportion of IBS patients, providing a biological rationale for microbiota-targeted therapeutic interventions”.

In addition, a subset of patients with IBS, particularly those with diarrhea-predominant symptoms, may exhibit small intestinal bacterial overgrowth (SIBO), a condition characterized by an excessive number and/or abnormal distribution of bacteria within the small intestine4. Although the precise causal relationships remain incompletely understood, accumulating evidence suggests that both dysbiosis and SIBO may contribute to symptom development in at least a proportion of IBS patients, providing a strong biological rationale for microbiota-targeted therapeutic interventions, such as diet, gut-directed antibiotics, probiotics, postbiotics, and, in selected cases, fecal microbiota transplantation (FMT)2,5.

 

What are the pros and cons of breath tests for detecting SIBO in patients with suggestive symptoms and risk factors?

SIBO refers to a clinical condition, characterized by malabsorption or/and gas-related symptoms. The key concept is that in SIBO bacteria move upstream into the small intestine, where they ferment carbohydrates before absorption can occur. This premature and excessive fermentation increases gas production and reduces nutrient absorption, leading to bloating, abdominal distension and flatulence. It is important to emphasize that SIBO is not simply a matter of bacterial quantity. A bacterial count above 10³ CFU/mL may define SIBO microbiologically, but the clinical consequences appear to depend largely on the type of bacteria present. When the overgrowth consists mainly of oral flora, intestinal permeability remains essentially normal. Conversely, contamination by colonic-type bacteria is associated with a significant increase in intestinal permeability, which may represent the primum movens of a series of pathophysiology events leading to symptom generation6.

While duodenal aspirate and culture remain the gold standard for diagnosing SIBO, their invasive nature and high cost limit their routine use. As a result, breath tests have become the most widely used diagnostic tools, with the glucose breath test generally providing greater sensitivity and diagnostic accuracy than the lactulose breath test. Different microbial ecosystems are linked to different clinical phenotypes, with hydrogen and hydrogen sulfide producers predominating in IBS-D, whereas methane-producing microorganisms are more frequently associated with IBS-C.

Thus, microbial composition and metabolic activity may be key determinants of symptom expression, rather than simply bacterial abundance. When properly performed, a positive breath test represents an important predictor of response to rifaximin. Indeed, in SIBO-positive IBS patients, global symptom relief is achieved in up to 70% of cases, compared with the 10% in unselected population7.

 

Which levels of gut microbiome manipulation exist in IBS?

The interventions for manipulating the gut microbiome in patients with IBS range from 1) microbiome modulation with diet and rifaximin, 2) microbial supplementation with probiotics, 3) administration of microbiota-derived products (postbiotics), and 4) complete ecosystem replacement by FMT.

Diet is the first, the safest and quickest method of microbiome manipulation. Examples include increased soluble fiber, reduction of highly processed food, Mediterranean diet and low-FODMAP diet. The principal effect of dietary modifications is not to change bacterial species directly but rather to modify substrate availability, microbial metabolism, short-chain fatty acid production, gas production, and bile acid metabolism. This represents ecological modulation rather than microbial replacement8.

“Diet is the first, the safest and quickest method for gut microbiome manipulation, representing ecological modulation rather than microbial replacement”.

The availability of gut-directed antibiotics has enabled the treatment of dysbiosis while avoiding many of the adverse consequences typically associated with systemic antimicrobial therapy. Experimental and clinical evidence indicate that rifaximin behaves as a eubiotic agent, meaning that it modulates microbial function without profoundly disrupting the overall microbial ecosystem9,10. In addition, it displays anti-inflammatory properties that are independent of its antimicrobial activity. Its favorable safety profile and minimal systemic absorption make it an attractive microbiota-targeted therapeutic option in selected patients with IBS, in whom it induces symptom relief that is sustained after treatment discontinuation11. Although current guidelines, including the recent Italian guidelines, suggest rifaximin use in IBS patients without constipation, there is a biologically plausible rationale for its use in selected patients with IBS-C, particularly those characterized by excessive methane production and prolonged colonic transit time12.

Probiotics represent another microbiota-directed therapeutic approach in IBS that may improve symptoms by restoring microbial balance, enhancing intestinal barrier function, modulating mucosal immune responses, and influencing gut–brain signaling. Although efficacy appears to be strain-specific and results across studies are heterogeneous, selected probiotic preparations have demonstrated beneficial effects on abdominal pain, bloating, and overall symptom burden in patients with IBS13. An evaluation of strain-specific and outcome-specific efficacy of probiotics in IBS concluded that only four probiotics demonstrated a significant reduction in abdominal pain: Bacillus coagulans MTCC5260, Lactiplantibacillus plantarum 299v, Saccharomyces boulardii CNCM I-745 and Saccharomyces cerevisiae CNCM I-385614.

“While the British Society of Gastroenterology, the World Gastroenterology Organization, and the more recent Italian guidelines consider probiotics a therapeutic option for global IBS symptoms, albeit with weak recommendations and low-quality evidence, the American College of Gastroenterology and the American Gastroenterological Association do not currently recommend their routine use because of insufficient and heterogeneous evidence”.

Growing evidence suggests that restoration of short-chain fatty acid (SCFA) production is associated with improvement in IBS symptoms and may represent an important therapeutic target. This is particularly relevant for diarrhea-predominant IBS, which is often characterized by a deficiency of SCFA-producing bacteria15. Among the various postbiotic compounds, butyric acid and its salts, particularly sodium butyrate, are the most extensively investigated owing to their beneficial effects on epithelial barrier integrity, mucosal immune regulation, intestinal inflammation, and visceral sensitivity16.

“Microbiota-directed therapies have a strong biological rationale in the treatment of IBS and other disorders of gut–brain interaction. Therapeutic success may depend less on which microorganisms are present than on what they do”.

Through these mechanisms, postbiotics may contribute to symptom improvement in IBS. A very recent meta-analysis showed that postbiotic interventions significantly improve abdominal pain and overall IBS severity while maintaining a safety profile comparable to placebo. Although the therapeutic potential of postbiotics has been recognized by the International Scientific Association for Probiotics and Prebiotics (ISAPP), major clinical guidelines do not currently recommend their use in the management of IBS.

FMT is a therapeutic strategy aimed at restoring intestinal microbial homeostasis through the transfer of a healthy donor’s fecal microbiota to a recipient. The most recent meta-analysis concluded that FMT may reduce IBS symptoms at 12 weeks compared with placebo, but the evidence remains very uncertain because of the considerable heterogeneity among studies, including differences in study design, FMT protocols, donor selection, and diagnostic criteria17. Future identification of predictors of response and standardization of donor selection, preparation procedures, and administration protocols may improve the consistency of clinical outcomes18.

 

Which are the more effective and safer strategies currently available for modifying the gut microbiome in IBS? And which are the less effective or less safe strategies available for modifying the gut microbiome in IBS?

The safest intervention is not necessarily the most effective, and the most effective intervention is not always the safest. The most natural and safe way to modify gut microbiota is certainly represented by diet. Nutraceuticals (i.e., selected probiotics and selected postbiotics) are effective but not in all IBS patients, with good safety profile, better for postbiotics, especially in vulnerable populations. From a pharmacological standpoint, rifaximin is very effective and safe, particularly those with SIBO or with putative SCFA- and bile acid-modifying taxa. FMT displays the greatest efficacy, allowing a complete microbiota replacement but with some safety concerns extending beyond conventional adverse events and including infectious, immunological, metabolic, and theoretical long-term risks.

However, IBS is a heterogeneous disorder in which microbiome-targeted interventions are unlikely to provide universal benefit. Precision-based approaches, taking into account IBS subtype, baseline microbiota composition, and dietary context, will therefore be essential to fully exploit their therapeutic potential. There is therefore no single “best” microbiome therapy for IBS. The optimal intervention depends on the patient’s clinical phenotype, underlying pathophysiology and microbial profile.

 

What will the next 10 years of gut microbiome research and clinical applications in IBS look like?

“We will probably stop treating IBS as a single disorder and instead manage biologically defined subgroups using personalized microbiome-based strategies”.

Over the next decade, gut microbiome research in IBS is expected to evolve from descriptive studies of dysbiosis toward precision microbiome medicine. Rather than focusing solely on taxonomic alterations, future investigations will increasingly emphasize microbial function, integrating metagenomics with metabolomics, transcriptomics, proteomics, and host immune profiling to identify clinically relevant microbial signatures and biomarkers predictive of treatment response.

This approach is expected to enable a more refined phenotyping of IBS, distinguishing subgroups characterized by specific pathophysiological mechanisms, such as altered bile acid metabolism, methane production, post-infectious dysbiosis, impaired intestinal barrier function, or disturbances of the gut–brain axis. Ultimately, we will probably stop treating IBS as a single disorder and instead manage biologically defined subgroups using personalized microbiome-based strategies.

 

Story source: The answers to the interview questions were provided by Prof. Carmelo Scarpignato. Note: Content may be edited for style and length.

 

References:

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