Gut Bacteria Encode Reductases that Biotransform Steroid Hormones.

The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the Δ-3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ isomerase, and Δ-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5β-reductase and Δ-3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5β- and Δ-reduced derivatives.

Gut Microbial Utilization of the Alternative Sweetener, D-Allulose, via AlsE.

D-allulose, a rare sugar with emerging potential as a low-calorie sweetener, has garnered attention as an alternative to other commercially available alternative sweeteners, such as sugar alcohols, which often cause severe gastrointestinal discomfort. D-allulose-6-phosphate 3-epimerase (AlsE) is a prokaryotic enzyme that converts D-allulose-6-phosphate into D-fructose-6-phopshate, enabling its use as a carbon source. However, the taxonomic breadth of AlsE across gut bacteria remains poorly understood, hindering insights into the utilization of D-allulose by microbial communities.

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen.

Metabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen.