Dysosmobacter: from a serendipitous discovery to a next-generation beneficial gut commensal linked to health

Dysosmobacter is a genus of strictly anaerobic, butyrate-producing bacteria of the family Oscillospiraceae that was first described in 2020 with the human faecal type species Dysosmobacter welbionis J115^T. The organism was recovered by chance during a targeted attempt to isolate new Subdoligranulum species, a project that failed in its original aim but yielded a bacterium that fulfilled the criteria for an entirely new genus. Since then, D. welbionis has emerged as one of the best-supported examples of a candidate next-generation beneficial microbe. It is carried by roughly two thirds to more than 90% of adults depending on the cohort and detection method, its faecal abundance correlates inversely with fasting glucose and glycated haemoglobin, and, in contrast to most microbiome markers, live supplementation of the type strain reproducibly improves diet-induced insulin resistance, brown adipose tissue thermogenesis and hepatic steatosis in mice. At the biochemical level D. welbionis is distinguished by a non-canonical route that converts myo-inositol to butyrate, by the production of bioactive lipids that act as peroxisome proliferator-activated receptor gamma agonists and by the capacity to convert cholesterol to poorly absorbed coprostanol. A rapidly growing body of clinical and veterinary literature now places Dysosmobacter at the crossroads of metabolic disease, liver disease, cardiovascular health, oncology, the gut-brain axis and drug-microbiome interactions. This review provides a comprehensive overview of the genus. It brings together its discovery, taxonomy, physiology and genomics, its ecology and prevalence in humans and animals, the mechanistic and preclinical evidence, the expanding catalogue of human disease associations and the prospects and hurdles for its development as a live biotherapeutic.