Gut Microbiome in Patients With Post-infectious Irritable Bowel Syndrome

Fondazione Policlinico Universitario Agostino Gemelli IRCCS315 enrolled

Overview

Observational, multicenter, prospective study aimed at characterizing the gut microbiome in patients with post-infectious irritable bowel syndrome (PI-IBS) using whole genome sequencing (WGS). The study will compare microbiome composition and function between PI-IBS patients and two control groups (post-infectious subjects without irritable bowel syndrome -IBS- and healthy controls), with the goal of identifying reproducible microbial signatures and target taxa associated with disease and symptom severity.

The human gut microbiome plays a key role in host physiology, including immune regulation, metabolism, and protection against pathogens. Alterations in microbiome composition (dysbiosis) have been associated with multiple diseases, including post-infectious irritable bowel syndrome (PI-IBS), a condition that develops after acute gastroenteritis and represents a well-defined model of microbiome disruption. MicroRestore-1 is a national, multicenter, prospective observational study designed to characterize the gut microbiome of patients with PI-IBS and identify microbial signatures associated with the disease. The study represents Aim 1 of a broader research program investigating precision microbiome modulation strategies. A total of 315 participants will be enrolled, including 105 PI-IBS patients, 105 post-infectious subjects without IBS, and 105 healthy controls. PI-IBS will be diagnosed according to Rome IV criteria. Eligible participants will undergo baseline clinical assessment, including symptom evaluation using the IBS Severity Scoring System (IBS-SSS), medical history, dietary habits, and lifestyle factors. Stool samples will be collected at baseline and, for PI-IBS patients, at monthly follow-up visits for three months. Control subjects will provide a single sample at enrollment. All samples will be processed and stored under standardized conditions and analyzed centrally. Microbiome analysis will be performed using whole genome shotgun sequencing, enabling high-resolution taxonomic and functional profiling. Bioinformatic and statistical analyses, including machine learning approaches, will be used to identify microbial signatures discriminating PI-IBS patients from controls and to explore associations between microbiome features and disease activity. The primary objective is to identify reproducible microbial signatures and target taxa associated with PI-IBS. Secondary objectives include comparing microbiome composition and function across study groups and evaluating correlations between microbiome features and symptom severity. This study is expected to provide foundational data for the development of precision microbiome-based therapeutic strategies in PI-IBS.

Study Type

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

PI-IBS patients (n = 105) * Inclusion criteria * Age ≥ 18 years old * PI-IBS diagnosed according to Rome IV criteria (33). * Diagnosis no earlier than 3 months before enrollment. * Written informed consent and compliance with study procedures. * Exclusion criteria * Chronic organic gastrointestinal (GI) disorders (e.g. Inflammatory Bowel Disease -IBD), metabolic syndrome, obesity, diabetes, GI cancers, systemic autoimmune disorders. * History of major abdominal surgery. Control cohort #1 - Post-infectious non-IBS (n = 105) * Inclusion criteria * Age ≥ 18 years old * History of acute infectious gastroenteritis \>6 months before enrollment. * Complete recovery without persistent GI symptoms. * Exclusion criteria * Current or past diagnosis of IBS. * Any chronic GI or systemic disorders. Control cohort #2 - Healthy subjects (n = 105) * Inclusion criteria * Age ≥ 18 years old * Healthy donors from FMT program or blood donor program. * No history of GI or systemic disorders. * Exclusion criteria * Any GI or systemic chronic condition. * Recent antibiotics/probiotics (\<4 weeks). * Chronic medication affecting microbiome composition (e.g. PPI)

Outcomes

Primary Outcomes

Identification of microbial signatures discriminating PI-IBS from controls

Identification of reproducible gut microbiome signatures, including taxonomic and functional profiles, that discriminate patients with post-infectious irritable bowel syndrome (PI-IBS) from control groups using whole genome shotgun sequencing and machine learning approaches.

Time frame: Baseline up to 30 months (end of study)

Secondary Outcomes

Association between microbiome features and disease severity

Evaluation of associations between gut microbiome composition and function and disease activity, as measured by the IBS Severity Scoring System (IBS-SSS).