Scientists have determined which genes in the probiotic Bifidobacterial longum increases the intestinal motility. They discovered that B. longum strains with the abfA cluster of genes can reduce constipation by improving the gut’s utilization of arabinan, an indigestible fiber.
One of the paper’s co-senior authors from the Qixiao Zhai of Jiangnan University said that they have recognized the causal connection between a genetic variant–the abfA cluster–to the key functional difference of probiotic B. longum in many model organisms, including mice and humans, and provided mechanistic and ecological insights into how a single gene cluster can affect the gut motility of hosts through arabinan metabolism.
Impaired gastrointestinal motility has been implicated in gut microbial dysbiosis, which is categorized by a substantial reductionin the plenty of useful microorganisms, some of which are conservatively known as probiotics. Orally administered probiotics have therefore been typically used to reduce symptoms.
Yet the therapeutic effect of probiotics for constipation often differs substantially across strains within the same species. Due to elusive mechanisms, the rational choice of probiotics remains challenging for patients and medical care professionals.
In addition, most indications on the beneficial effects of probiotics on gut motility mainly emerged from studies using a mouse model.
The study’s second co-senior author, Jiachao Zhang from Hainan University said that, Probiotic strains were often effective in animal models but failed in human clinical trials or were poorly validated in humans. Proof-of-concept trials built on a human cohort in combining with evidence from animal studies are required for translational study.
Zhai, Zhang, and Shi Huang of the University of Hong Kong, the document’s third co-senior author, set out to recognize and methodically authenticate the key genetic influences of exogenous probiotics or resident gut microbiota affecting gastrointestinal motility. They isolated 185 B. longum strains from 354 Chinese individuals who ranged in age from 0 to 108 years.
From a comprehensive library of wild B. longum strains, they discovered that the active alleviation of constipation in mice is controlled by the abfA cluster. This key genetic factor preferentially improves the utilization of arabinan–a common constituent of plant polysaccharides, an indigestible fiber for humans, and a poorly accessible source of nutrients for normal gut microbes.
The scientists further authenticated the abfA cluster’s practical roles using gene-knockout tests. In mice with constipation, B. longum, but not an abfA mutant, enhanced gastrointestinal transit time, an effect that was reliant on dietary arabinan.
To establish its functional roles for ameliorating constipation in humans, the scientists used a clinical trial and a human-to-mouse faecal microbiota transplantation experiment in combination with metagenomics and metabolomics.
Across human cohorts, abfA-cluster abundance in the faecal microbiomes forecast transplantation and constipation of abfA cluster-enriched human microbiota to mice with constipation enhanced gut motility.
Notably, other than B. longum, the abfA gene/cluster is prevalent in gut residents, regulating symptoms in both humans and mice. The authors informs that the abfA cluster is a gut-microbiome therapeutic mark for constipation in humans. However, the results suggest that genetic factors governing the unique metabolic capability of probiotics should be mainly considered for screening probiotics or inferring their treatment efficacy for gastrointestinal diseases.
Huang said that, collectively, this study identified and systematically characterized a key genetic factor responsible for arabinan utilization that addressed one critical challenge in the probiotic field, namely widespread yet unknown strain specificity in probiotic treatment efficacy.
Our proof-of-concept study also recognized generalizable principles for the rational development of colonizable, functional probiotics with persistent treatment efficacy in many model organisms. Additionally, the abfA cluster is so prevalent in the gut microbiota which can be developed as a simple yet powerful biomarker for gastrointestinal diseases.
