Effect of Intestinal Carriage of *Pilosibacter Rotomagensis* on Intestinal Inflammatory Activity

Condition(s) studied

Investigational drug(s) / intervention(s)

Microbiota suspension: If the patient agrees to participate, the stool sample will be used for both fecal calprotectin analysis (standard care) and the analysis of gut microbiota and short-chain fatty acids (research protocol). The purpose of this stool collection is to address the primary and secondary objectives of the present study.

Study summary

Crohn's disease is a chronic inflammatory condition that can affect the entire digestive tract. The terminal ileum is the segment most frequently involved, and approximately one-third of patients present with disease limited to the ileum. In such cases, surgical resection to remove all inflammatory lesions may be performed. This procedure prevents recurrence in about 50% of patients within five years of surgery.

The post-operative setting offers a prime opportunity to study the early pathophysiological stages of Crohn's disease and the risk factors for recurrence. While smoking is a well-established risk factor for recurrence, the role of other factors-such as a fistulizing phenotype or a history of small-bowel resection-remains a subject of debate. Meanwhile, the role of the gut microbiota in this process remains largely unclear. Currently, the prevention of post-operative recurrence relies exclusively on smoking cessation and biologic therapies. However, the efficacy of these biologics-particularly anti-TNFα (Tumor Necrosis Factor alpha) agents-is reduced in patients who received prior treatment with these drugs before surgery. Notably, the proportion of such pre-treated patients has risen over the last two decades, reaching 50%. Consequently, there is a need to expand the range of strategies available to prevent post-operative recurrence. A better understanding of host-gut bacteria interactions could help prevent postoperative recurrence. To date, only \*Faecalibacterium prausnitzii\* and Adherent-Invasive \*Escherichia coli\* (AIEC) have been associated with a lower and higher risk of postoperative recurrence, respectively. However, a randomized controlled trial showed that antibiotic treatment aimed at eradicating AIEC was no more effective than a placebo in Crohn's disease. These trial results reinforce the value of a strategy based on identifying anti-inflammatory bacterial species that may play a protective role against postoperative recurrence.

\*Pilosibacter rotomagensis\* is a bacterial species recently isolated from humans by the INSERM U1073 team; it may play a key role in intestinal physiology. This species is distinguished by its high capacity to produce short-chain fatty acids-particularly butyrate-and by anti-inflammatory properties observed in various \*in vitro\* cellular models.

The hypothesis of this project is that carriage of \*Pilosibacter rotomagensis\* could play a protective role against postoperative recurrence in ileal Crohn's disease.

Eligibility

Primary outcome measure(s)

• Association between intestinal inflammatory activity and the carriage rInvestigating the aate of *Pilosibacter rotomagensis — 1 day
  Investigating the association between intestinal inflammatory activity and the carriage rate of \*Pilosibacter rotomagensis following resection for isolated ileal Crohn's disease by measuring fecal calprotectin levels

Trial sites (1)

More University Hospital, Rouen trials in France