Breakthrough discovery: Key genes in probiotic B. longum unveiled, paving the way for targeted constipation relief

Texas: Researchers have pinpointed the specific genes within the probiotic Bifidobacterium longum that enhance intestinal motility, potentially reducing constipation. The study, published in the journal Cell Host & Microbe, reveals that B. longum strains with the abfA cluster of genes play a key role in promoting the gut's utilization of arabinan, an indigestible fiber.

Qixiao Zhai, co-senior author of the paper and a researcher at Jiangnan University, explains, "We established the causal link between a genetic variant—the abfA cluster—and the key functional difference of probiotic B. longum in multiple model organisms, including mice and humans, providing mechanistic and ecological insights into how a single gene cluster can affect the gut motility of hosts through arabinan metabolism."

Gastrointestinal motility issues are linked to gut microbial dysbiosis, characterized by a decrease in beneficial microorganisms, some of which are probiotics. Although probiotics are commonly used to alleviate symptoms, their effectiveness varies among strains within the same species. The study aims to address the elusive mechanisms behind this variability.

Gastrointestinal motility

Jiachao Zhang, the study's second co-senior author from Hainan University, highlights the need for "proof-of-concept studies based on a human cohort in combination with evidence from animal studies" to guide translational research.

The researchers, including Shi Huang from the University of Hong Kong, identified and validated key genetic factors affecting gastrointestinal motility by isolating 185 B. longum strains from 354 Chinese subjects. They found that the abfA cluster regulates constipation relief in mice by enhancing arabinan utilization.

Gene-knockout experiments further validated the abfA cluster's role in improving gastrointestinal transit time in mice with constipation. A clinical trial and human-to-mouse fecal microbiota transplantation experiments, combined with metagenomics and metabolomics, confirmed the abfA cluster's functional roles in alleviating constipation in humans.

Therapeutic target for constipation in humans

Supplementation with abfA-cluster-carrying B. longum enriched arabinan-utilizing residents, increased beneficial metabolites, and improved constipation symptoms in the clinical trial. The abfA cluster's prevalence in gut residents suggests it as a potential therapeutic target for constipation in humans and a biomarker for gastrointestinal diseases.

Shi Huang emphasizes the study's broader implications, stating, "Our proof-of-concept study also established generalizable principles for the rational development of colonizable, functional probiotics with persistent treatment efficacy in multiple model organisms."