Qixing Nie

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human gut. Accumulating evidence suggests that dietary fiber plays a crucial role in host health, yet most studies have focused on how the dietary fiber affects health through gut Bacteroides. More recently, gut Firmicutes have been found to possess many genes responsible for fermenting dietary fiber, and could also interact with the intestinal mucosa and thereby contribute to homeostasis. Consequently, the relationship between dietary fiber and Firmicutes is of interest, as well as the role of Firmicutes in host health. In this review, we summarize the current knowledge regarding the molecular mechanism of dietary fiber degradation by gut Firmicutes and explain the communication pathway of the dietary fiber-Firmicutes-host axis, and the beneficial effects of dietary fiber-induced Firmicutes and their metabolites on health. A better understanding of the dialogue sustained by the dietary fiber-Firmicutes axis and the host could provide new insights into probiotic therapy and novel dietary interventions aimed at increasing the abundance of Firmicutes (such as Faecalibacterium, Lactobacillus, and Roseburia) to promote health.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as β-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.