A Shigella species variant is causally linked to intractable functional constipation

Area of Science:

• Gastroenterology
• Microbiology
• Pathogen Discovery

Background:

• Intractable functional constipation (IFC) is a severe form of constipation with an unknown cause.
• Previous research has not identified the specific etiology of IFC.

Purpose of the Study:

• To investigate the hypothesis that IFC results from infection by a pathogenic bacterium.
• To identify the causative agent and mechanism behind IFC.

Main Methods:

• Isolation and identification of bacteria from IFC patients.
• In vitro and in vivo studies using bacterial isolates and animal models.
• Analysis of bacterial metabolites, specifically docosapentenoic acid (DPA).
• Detection of bacteria and DPA in patient stool samples.

Main Results:

• A Shigella species, named peristaltic contraction-inhibiting bacterium (PIB), was isolated from IFC patients.
• PIB inhibited colonic peristalsis via DPA production, inducing constipation in mice.
• PIB-specific phages reversed constipation.
• PIB was detected in 56% of IFC patients but not in controls.
• Elevated DPA levels were found in 44.12% of IFC patients but not in controls.

Conclusions:

• Shigella sp. PIB is identified as a critical causative pathogen for IFC.
• Fecal PIB and DPA detection offers a reliable diagnostic method for IFC.
• This discovery opens new avenues for understanding and classifying constipation.