Stephen J. Keely

This study reveals a previously unrecognized role for lithocholic acid (LCA) in chronically suppressing colonic epithelial chloride secretion. We demonstrate a genomic mechanism of action for LCA that is likely mediated by FXR-induced downregulation of CFTR expression and function. These findings highlight LCA as a key modulator of intestinal fluid and electrolyte transport and underline the therapeutic potential of targeting bile acids and their receptors for the treatment of diarrheal diseases.

These studies demonstrate for the first time that FXR activation inhibits cytokine-induced necroptosis in vitro, an effect that may underlie protection against dysregulated barrier function in the setting of intestinal inflammation. These data support the potential for targeting FXR to promote epithelial barrier function in treatment of IBD.

The complex microbial community residing in the human gut has long been understood to regulate gastrointestinal physiology and to participate in digestive diseases, but its extraintestinal actions and influences are increasingly recognized. This article discusses bidirectional interactions between the gut microbiome and athletic performance, metabolism, longevity and the ability of the gut–brain axis to influence cognitive function and mental health. image

Activation of the nuclear bile acid receptor, farnesoid X receptor (FXR), specifically upregulates ACE2 expression in undifferentiated colonic epithelial cells and inhibits virus-induced proinflammatory cytokine release. By virtue of these actions FXR represents a promising target for the development of new approaches to prevent intestinal manifestations of SARS-CoV-2 infection.

Bile salt hydrolase (BSH) and penicillin V acylase (PVA) are related enzymes that are classified as choloylglycine hydrolases (CGH). BSH enzymes have attracted significant interest for their ability to modulate the composition of the bile acid pool, alter bile acid signaling events mediated by the host bile acid receptors FXR and TGR5 and influence cholesterol homeostasis in the host, while PVA enzymes have been widely utilised in an industrial capacity in the production of semi-synthetic antibiotics. The similarities between BSH and PVA enzymes suggest common evolution of these enzymes and shared mechanisms for substrate binding and catalysis. Here, we compare BSH and PVA through analysis of the distribution, phylogeny and biochemistry of these microbial enzymes. The development of new annotation approaches based upon functional enzyme analyses and the potential implications of BSH enzymes for host health are discussed.

Bacterial metabolism of UDCA to LCA protects against DSS‐induced colonic inflammation by preventing epithelial apoptosis and promoting barrier function. In conditions of IBD, increased production of ...