Pangenome analysis of : a collection of diverse bile acid and steroid metabolizing commensal gut bacterial strains.

is a commensal gut bacterium capable of forming the secondary bile acids deoxycholic acid and lithocholic acid from the primary bile acids cholic acid and chenodeoxycholic acid, respectively, as well as converting glucocorticoids to androgens. Historically, only two strains, ATCC 35704 and VPI 12708, have been characterized and to any significant extent. The formation of secondary bile acids is important in maintaining normal gastrointestinal function, in regulating the structure of the gut microbiome, in the etiology of such diseases such as cancers of the GI tract, and in the prevention of infection.

: an endocrine keystone species in the mammalian gut.

is a keystone human gut microbial taxonomic group that, while low in abundance, has a disproportionate effect on bile acid and steroid metabolism in the mammalian gut. Numerous studies indicate that the two most studied strains of (i.e.

Another renaissance for bile acid gastrointestinal microbiology.

The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota.

The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology.

Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived "primary" bile acids from "secondary" bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction.

Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes.

The gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B- orientation in which the sterol rings are "kinked", as well as small quantities of A/B- oriented "flat" stereoisomers known as "primary allo-bile acids". While the complex multi-step bile acid 7α-dehydroxylation pathway has been well-studied for conversion of "kinked" primary bile acids such as cholic acid (CA) and chenodeoxycholic acid (CDCA) to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, the enzymatic basis for the formation of "flat" stereoisomers allo-deoxycholic acid (allo-DCA) and allo-lithocholic acid (allo-LCA) by Firmicutes has remained unsolved for three decades.

Feeding mode influences dynamic gut microbiota signatures and affects susceptibility to anti-CD3 mAb-induced intestinal injury in neonatal mice.

Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of β-diversity including expansion of and in the ileum of FF pups compared with DF pups by postnatal day (P)2.

Diversity and distribution of sulfur metabolic genes in the human gut microbiome and their association with colorectal cancer.

Background: Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Microbial sulfidogenesis produces genotoxic hydrogen sulfide (HS) in the human colon using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates; however, the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr).

Results: Here, we show that genes for microbial sulfur metabolism are more abundant and diverse than previously observed and are statistically associated with CRC.

Sas20 is a highly flexible starch-binding protein in the Ruminococcus bromii cell-surface amylosome.

Ruminococcus bromii is a keystone species in the human gut that has the rare ability to degrade dietary resistant starch (RS). This bacterium secretes a suite of starch-active proteins that work together within larger complexes called amylosomes that allow R. bromii to bind and degrade RS.

Special Issue: Microbial Impact on Cholesterol and Bile Acid Metabolism.

An important current focus in microbiome science is the biotransformation and degradation of cholesterol, steroids, and bile acids [...

Bile Acids, Gut Microbes, and the Neighborhood Food Environment-a Potential Driver of Colorectal Cancer Health Disparities.

Bile acids (BAs) facilitate nutrient digestion and absorption and act as signaling molecules in a number of metabolic and inflammatory pathways. Expansion of the BA pool and increased exposure to microbial BA metabolites has been associated with increased colorectal cancer (CRC) risk. It is well established that diet influences systemic BA concentrations and microbial BA metabolism.

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine.

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcription factor farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood.

Support policies that foster a healthy food environment and incentivize healthy food purchases to mitigate cancer inequities.

The COVID-19 pandemic has highlighted the inequitable access to resources, leading to a disproportionate burden of disease in vulnerable communities in the USA. However, these inequities in health outcomes are not limited to COVID-19. Approximately 18% of cancers are related to dietary behaviors and excess body weight.

Completion of the gut microbial epi-bile acid pathway.

Bile acids are detergent molecules that solubilize dietary lipids and lipid-soluble vitamins. Humans synthesize bile acids with α-orientation hydroxyl groups which can be biotransformed by gut microbiota to toxic, hydrophobic bile acids, such as deoxycholic acid (DCA). Gut microbiota can also convert hydroxyl groups from the α-orientation through an oxo-intermediate to the β-orientation, resulting in more hydrophilic, less toxic bile acids.

Bariatric surgery stirs symbionts to counteract diabesity by CA(7)Sting a liver-generated bile acid into the mix.

Obesity and diabetes are major health challenges for the 21 century. Effective treatments affect nutrient signaling along the gut microbiome-bile acid axis. In this issue of Cell, Chaudhari et al.

Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega.

Bile acids (BAs) and glucocorticoids are steroid hormones derived from cholesterol that are important signaling molecules in humans and other vertebrates. Hydroxysteroid dehydrogenases (HSDHs) are encoded both by the host and by their resident gut microbiota, and they reversibly convert steroid hydroxyl groups to keto groups. Pairs of HSDHs can reversibly epimerize steroids from α-hydroxy conformations to β-hydroxy, or β-hydroxy to ω-hydroxy in the case of ω-muricholic acid.

Development of a novel model of cholecystectomy in subsequently ovariectomized mice and characterization of metabolic and gastrointestinal phenotypes: a pilot study.

Background: Cholecystectomy (XGB) is the most common abdominal surgery performed in the United States and is associated with an increased post-surgery incidence of metabolic and gastrointestinal (GI) diseases. Two main risk factors for XGB are sex (female) and age (40-50 yr), corresponding with onset of menopause. Post-menopausal estrogen loss alone facilitates metabolic dysfunction, but the effects of XGB on metabolic and GI health have yet to be investigated in this population.

Gut feelings about bacterial steroid-17,20-desmolase.

Advances in technology are only beginning to reveal the complex interactions between hosts and their resident microbiota that have co-evolved over centuries. In this review, we present compelling evidence that implicates the host-associated microbiome in the generation of 11β-hydroxyandrostenedione, leading to the formation of potent 11-oxy-androgens. Microbial steroid-17,20-desmolase cleaves the side-chain of glucocorticoids (GC), including cortisol (and its derivatives of cortisone, 5α-dihydrocortisol, and also (allo)- 3α, 5α-tetrahydrocortisol, but not 3α-5β-tetrahydrocortisol) and drugs (prednisone and dexamethasone).

The gut bacterium produces secondary bile acids and influences liver physiology in gnotobiotic mice.

is a newly described mouse gut bacterium which metabolizes cholic acid (CA) to deoxycholic acid (DCA) via 7α-dehydroxylation. Although bile acids influence metabolic and inflammatory responses, few models exist for studying their metabolism and impact on the host. Mice were colonized from birth with the simplified community Oligo-MM with or without .

A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity.

Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera.

Infection with Bacteroides Phage BV01 Alters the Host Transcriptome and Bile Acid Metabolism in a Common Human Gut Microbe.

Gut-associated phages are hypothesized to alter the abundance and activity of their bacterial hosts, contributing to human health and disease. Although temperate phages constitute a significant fraction of the gut virome, the effects of lysogenic infection are underexplored. We report that the temperate phage, Bacteroides phage BV01, broadly alters its host's transcriptome, the prominent human gut symbiont Bacteroides vulgatus.

Effects of taurocholic acid metabolism by gut bacteria: A controlled feeding trial in adult African American subjects at elevated risk for colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer and second leading cause of cancer death in the United States. Recent evidence has linked a high fat and animal protein diet and microbial metabolism of host bile acids as environmental risk factors for CRC development. We hypothesize that the primary bile salt taurocholic acid (TCA) is a key, diet-controlled metabolite whose use by bacteria yields a carcinogen and tumor-promoter, respectively.

Conceptualizing the Vertebrate Sterolbiome.

Vertebrates synthesize a diverse set of steroids and bile acids that undergo bacterial biotransformations. The endocrine literature has principally focused on the biochemistry and molecular biology of host synthesis and tissue-specific metabolism of steroids. Host-associated microbiota possess a coevolved set of steroid and bile acid modifying enzymes that match the majority of host peripheral biotransformations in addition to unique capabilities.