# The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option

## TL;DR

This study explores how gut bacteria may contribute to chronic intestinal pseudo-obstruction and shows that fecal microbiota transplantation can improve symptoms in mice and a human patient.

## Contribution

The study demonstrates that fecal microbiota transplantation can alleviate CIPO symptoms in mice and a patient by restoring gut microbiota balance.

## Key findings

- CIPO microbiota has reduced diversity and is dominated by Proteobacteria.
- Mice with CIPO microbiota show bowel distension and slow transit, linked to gene expression changes.
- FMT from healthy donors improved microbiota, intestinal function, and symptoms in mice and a CIPO patient.

## Abstract

Chronic intestinal pseudo-obstruction (CIPO) is characterized by bowel dilation and obstructive symptoms without any structural blockage. Although the microbiota is known to affect gastrointestinal function, its role in CIPO is poorly understood. We aimed to characterize the CIPO microbiota, investigate its role in disease expression and explore the therapeutic role of fecal microbiota transplantation (FMT). CIPO patients (n = 14) and healthy controls (HC, n = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.