D1.344 - Role of nodular lymphoid hyperplasia as immunologic precursor of IBD development in patients with IBS-like symptoms: an observational, ambispectic, muliticenter study “The NILO study”

Irritable bowel syndrome (IBS) and chronic inflammatory bowel diseases (IBD) share overlapping pathophysiological mechanisms, including dysbiosis, impaired intestinal barrier function, and immune dysregulation, while maintaining distinct clinical and diagnostic profiles. Lymphoid follicular hyperplasia (LFH), detectable through ileocolonoscopy and histopathology in IBS-like patients, represents an immunological alteration potentially indicative of a preclinical phase of IBD. However, the prognostic value of LFH remains poorly characterized, warranting further investigation into its utility as a biomarker for IBD progression.

The primary objective is to evaluate the incidence and risk factors of IBD development in IBS-like patients with LFH by characterizing their immunophenotypic profiles. Secondary aims include the identification of molecular, serological, and fecal biomarkers associated with LFH and the assessment of gut microbiota composition and intestinal epithelial barrier integrity.

This multicenter, ambispective, observational cohort study includes a retrospective phase (2011–2023) and a prospective phase with a 10-year follow-up. The study population comprises adults aged 18–70 years, categorized into three cohorts: (1) IBS-like patients with diffuse ileal and/or colonic LFH; (2) IBS-like patients with LFH associated with IBD; and (3) IBS-like patients without LFH (control group).

The study integrates clinical, endoscopic, histopathological, and biomarker data. Serological (e.g., C-reactive protein, serum zonulin), fecal (e.g., calprotectin), and molecular biomarkers will be analyzed. Gut microbiota composition will be characterized using high-throughput sequencing technologies. Immunophenotypic profiling of peripheral blood and intestinal biopsy samples will identify immune cell subsets and activation markers associated with LFH. Statistical analyses, including multivariate regression and survival models, will evaluate predictors of IBD progression.

The study aims to establish LFH as an early immunological marker of IBD progression, identifying specific biomarkers and immune profiles (e.g., IgG subclasses, eosinophil cationic protein, C-reactive protein, IgA, IgG, IgM, total IgE, and specific IgE for staphylococcal enterotoxins, Alt a 1, Aspergillus fumigatus, and Alternaria alternata) and lymphocyte typing, that may predict the transition from IBS-like symptoms to chronic intestinal inflammation.

This study aims to elucidate the pathophysiological role of LFH in IBS-like conditions and its progression to IBD. Early identification of high-risk individuals could enable precision medicine approaches, fostering targeted preventive and therapeutic strategies in chronic intestinal disorders.