Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

Abstract

Bile salt hydrolases (BSHs) catalyze the ''gateway'' reaction in a wider pathway of bile acid modification by the gut microbiota. Because bile acids function as signaling molecules regulating their own biosynthesis, lipid absorption, cholesterol homeostasis, and local mucosal defenses in the intestine, microbial BSH activity has the potential to greatly influence host physiology. However, the function, distribution, and abundance of BSH enzymes in the gut community are unknown. Here, we show that BSH activity is a conserved microbial adaptation to the human gut environment with a high level of redundancy in this ecosystem. Through metagenomic analyses we identified functional BSH in all major bacterial divisions and archaeal species in the gut and demonstrate that BSH is enriched in the human gut microbiome. Phylogenetic analysis illustrates that selective pressure in the form of conjugated bile acid has driven the evolution of members of the NtnCGH-like family of proteins toward BSH activity in gut-associated species. Furthermore, we demonstrate that BSH mediates bile tolerance in vitro and enhances survival in the murine gut in vivo. Overall, we demonstrate the use of function-driven metagenomics to identify functional anchors in complex microbial communities, and dissect the gut microbiome according to activities relevant to survival in the mammalian gastrointestinal tract.bile modification ͉ microbiota ͉ functional anchor ͉ GI survival

‘The way to a man's heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk

“…They also proposed the term 'metabolic endotoxemia' to describe the chronic low-grade systemic inflammation characteristic of obesity and type 2 diabetes (16) . Improved gut barrier activity resulted from prebiotic induction of the gut hormone glucagon-like peptide-2, a result confirmed in a later animal experiment (78) . More recently, Everard et al (155) confirmed Cani's earlier work that the prebiotic oligofructose could reduce gut permeability and associated metabolic endotoxemia and obesity in high-fat-fed animals through induction of intestinal endocannabinoids.…”

“…Similarly, SCFA have been shown to regulate adipocyte hormone production, not least of leptin (75) , the obesity hormone, and to control inflammatory processes in adipose tissue (76) , processes intimately involved in CVD risk, and possibly also impact on the way energy is stored or burnt in the body controlling adiposity and thermogenesis (15,77) . Microbial deconjugation of BA and the enterohepatic circulation of BA is a core activity of the human gut microbiota and is thought to directly regulate cholesterol levels in the blood (78,79) . Conjugated BA are secreted into the small intestine to aid micelle formation and fat absorption.…”

Temporal variation selects for diet–microbe co-metabolic traits in the gut of Gorilla spp

“…Thus, these data may also provide hints to possible energy storage mechanisms in lowland gorillas, similar to those taking place in humans under high-caloric diets (Jones et al, 2008;Martin et al, 2007). Furthermore, fat deposition and storage are important evolutionary discriminant features between humans and non-human primates (Horrobin, 1999;Navarrete et al, 2011).…”

Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial

“…7,8,11 Follow-up studies confirmed that germ-free animals have elevated conjugated bile acids throughout the intestine with no deconjugation and strongly decreased fecal excretion. 9 It has been hypothesized that increases in deconjugated bile acids may result in reduced farnesoid X receptor activation, increased cholesterol catabolism, reduced inhibition of liver X receptor (LXR) and upregulation of adenosine triphosphate-binding cassette (ABC)G5/G8 transporters. These transporters efflux cholesterol from hepatocytes and enterocytes 18 and are stimulated in the presence of deconjugated bile acids.…”

“…8 This was substantiated by showing that germ-free animals have elevated levels of conjugated bile acids throughout the intestine, significantly reduced fecal biliary excretion and three times the bile-acid concentration in bile. [9][10][11] Further, it was shown that mice treated with oral antibiotics for 3 days increased biliary bile-acid output threefold, whereas fecal output decreased by 70%. 12 In addition, porcine studies have demonstrated that increasing the bile salt hydrolase (BSH) activity of the intestinal microflora results in a significant increase in the deconjugated bile-acid pool 13 and a reduction in circulating cholesterol.…”