Bile salt hydrolases: Gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract.
Foley MH, O'Flaherty S, Barrangou R, Theriot CM
PLoS Pathog. 03 2019. doi: 10.1371/journal.ppat.1007581
COMMENT: Bile salts hydrolases (BSH) are homotetrameric proteins predominantly expressed in the bacterial cytoplasm. Their function is to initiate bile acids metabolism by the hydrolysis and deconjugation of bile acids. Deconjugated bile acids can generate secondary bile acids, which have important effects in the host and resident microbiota. So, BSH enzymes could be a tool to manipulate the microbiota. The authors summarize the current knowledge of BSH enzymes and discuss their potential to impact the microbiome, host physiology and disease.
About the influence of BSHs on the composition of the GIT microbiota:
The broad distribution and abundance of BSHs in the GIT suggests that bile acid deconjugation is a selected adaptive trait of several bacterial species for symbiosis or pathogenesis within the host.
Bacterial pathogens, like some commensals, use BSHs to persist and survive during host infection. Brucella abortus BSH activity leads to membrane modifications resisting phagocytosis and Listeria monocytogenes exploits its BSH for survival in the bile acid-rich liver and gall bladder. Alternatively, BSH activity can provide protection from pathogens. Microbiome-encoded BSHs and secondary bile acid metabolism are associated with colonization resistance against pathogens such as Clostridioides difficile.
The bile acid pool, influenced in part by microbial-encoded BSHs, in turn shapes the microbiome composition and function. This bidirectional relationship can occur directly through inhibiting the growth of bile acid susceptible species or by inducing the germination of others. Indirectly, bile acids can modulate the expression of host intestinal innate immune factors such as intestinal antimicrobial peptides and inducible nitric oxide synthase (iNOS) that select for certain gut inhabitants. Deconjugated bile acids alone have been shown to drive phylum level shifts favoring the firmicutes at the expense of the bacteroidetes.
Bile acid dysregulation has been implicated in diseases such as nonalcoholic fatty liver disease, liver tumorigenesis and autism spectrum disorder, though the role of BSHs in their etiology is not well understood.
Given that a single bacterial enzyme can have a profound impact on human health and disease, there are many unanswered questions regarding BSH biology that need to be addressed before this enzyme can be used as a therapeutic tool.