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

The CIPO microbiota exhibited reduced microbial diversity compared to healthy controls.

• CIPO patients (n=14) and healthy controls (HC, n=12) were recruited from Italy and Canada.
• Microbiota profiles were assessed by 16S rRNA sequencing.
• The CIPO microbiota showed dominance of Proteobacteria relative to healthy controls.
• Metabolic functions were also altered in the CIPO microbiota as assessed by PICRUSt.

Germ-free mice colonized with CIPO microbiota developed marked bowel distension and slow intestinal transit.

• Germ-free NIH Swiss mice were colonized with either HC or CIPO microbiota.
• Intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT).
• Mice colonized with CIPO microbiota developed marked bowel distension compared to HC microbiota-colonized mice.
• Slow intestinal transit was observed in CIPO microbiota-colonized mice.

CIPO microbiota-colonized mice showed altered expression of multiple genes related to immunity, the intestinal barrier, and neuromuscular function.

• Gene expression was assessed using NanoString® technology.
• Altered gene expression was observed across categories including immunity, intestinal barrier function, and neuromuscular function.
• These changes were associated with the bowel distension and slow intestinal transit phenotype observed in CIPO microbiota-colonized mice.

FMT from a healthy control improved microbiota profile, intestinal transit, and bowel distension in CIPO microbiota-colonized mice.

• FMT was performed using fecal material from a healthy control donor.
• Following FMT, mice showed improvement in intestinal transit as assessed by videofluoroscopy.
• Bowel distension was reduced following FMT as assessed by CT.
• The microbiota profile of CIPO mice improved following FMT from a healthy control.

A single CIPO patient treated with FMT from a healthy control experienced marked clinical improvement sustained for 8 years.

• The FMT was performed on a selected CIPO patient.
• Clinical improvement included improvement in the microbiota profile following FMT.
• The clinical improvement was described as 'marked' and was sustained for 8 years post-FMT.
• This finding in the patient was consistent with the results observed in the mouse model.

The gut microbiota plays a functional role in disease expression of CIPO, as demonstrated by the germ-free mouse colonization model.

• Germ-free NIH Swiss mice were used to isolate the effect of the microbiota from other host factors.
• Colonization with CIPO microbiota was sufficient to recapitulate key features of CIPO including bowel distension and slow transit.
• This causal relationship supports the microbiota as a contributor to CIPO disease expression rather than merely an association.
• The findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.