What is already known
Constipation — a condition characterized by uncomfortable or infrequent bowel movements — affects about 10% to 15% of people worldwide. Beneficial gut microorganisms, some of which are known as probiotics, are often used to relieve constipation. However, their effect is variable and the mechanisms through which they ease gut motility remain elusive.
What this research adds
Researchers isolated 185 strains of the probiotic Bifidobacterium longum from 354 people and found that a cluster of genes called abfA reduced constipation in mice. The abfA cluster appeared to improve the gut’s utilization of arabinan, an indigestible fiber commonly found in sugar beet, seeds and roots. In humans, the abundance of the abfA cluster in gut microbiotas predicted constipation, and transferring microbiota enriched in abfA cluster from humans to constipated mice improved the animals’ gut motility.
Conclusions
The findings suggest that the genetic features of bacteria should be taken into account when screening for probiotics to treat gastrointestinal conditions. The work also indicates that the abfA cluster might be used as therapeutic target for constipation in humans.
Constipation — a condition characterized by uncomfortable or infrequent bowel movements — affects about 10% to 15% of people worldwide. Researchers have now identified the genes that allow the beneficial microbe Bifidobacterium longum to enhance gut motility.
The findings, published in Cell Host & Microbe, suggest that a specific cluster of microbial genes might be used as therapeutic target for constipation in humans.
Bifidobacterium longum and other beneficial gut microorganisms known as probiotics are often used to relieve constipation. However, their effect is variable and the mechanisms through which they ease gut motility remain elusive.
“Probiotic strains were often effective in animal models yet failed in human clinical trials or were poorly validated in humans,” says study co-author Jiachao Zhang at Hainan University in Haikou, China. “Proof-of-concept studies based on a human cohort in combination with evidence from animal studies are urgently needed for translational research.”
To work out how gut bacteria can help relieve constipation, Zhang and his colleagues isolated 185 strains of Bifidobacterium longum from 354 people.
Genetic factor
By comparing the genetic features of several strains of B. longum, the researchers discovered that a cluster of genes called abfA reduced constipation in mice. The abfA cluster improves the gut’s utilization of arabinan, an indigestible fiber commonly found in sugar beet, seeds and roots, the team found.
Arabinan is typically a poorly accessible source of nutrients for gut microbes, but not for microbes that carry the abfA cluster, the authors say. “This abfA cluster confers B. longum a unique arabinan-utilization ability, facilitating their adaptation and colonization to host gut.”
To further investigate the role of abfA in relieving constipation, the team transferred microbiota enriched in abfA cluster from humans to constipated mice. The procedure improved the mice’s gut motility and increased the levels of beneficial metabolites.
Constipation biomarker
The abundance of the abfA cluster in gut microbiotas could predict people who suffered from constipation, suggesting that abfA-cluster abundance may be used as a biomarker of constipation.
The results indicate that the genetic features of bacteria should be taken into account when screening for probiotics to treat gastrointestinal conditions. “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,” the researchers say. “These findings demonstrate a role for microbial abfA cluster in ameliorating [constipation], establishing principles for genomics-directed probiotic therapies.”
The work, they add, also highlights how examining genetic deficits for digesting dietary fiber in the human gut microbiota may help to fight many other conditions caused by microbial dysbiosis.
