Dataset Information

Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium Christensenella minuta.

ABSTRACT: Christensenella minuta are human gut dwelling bacteria that have been proposed as key members of the gut microbiome, regulating energy balance and adiposity of their host. We formerly identified that a novel strain of C. minuta (strain DSM33407) boosted microbiota diversity and stimulated deconjugation of the primary bile acid taurocholic acid in human samples. However, there is no description of a bile salt hydrolase (BSH) protein carried in the genome of C. minuta. Here, we identified and cloned a protein from C. minuta's genome that carries a potent BSH activity, which preferentially deconjugates glycine-conjugated bile acids. We then retrieved 14,319 putative BSH sequences from the NCBI database and filtered them using the UHGP database to collect a total of 6701 sequences that were used to build the most comprehensive phylogenetic tree of BSH-related enzymes identified in the human microbiome so far. This phylogenetic tree revealed that C. minuta's BSH amino acid sequence clusters away from others with a threshold of 70% identity. This is therefore the first description of C. minuta's BSH protein, which may be involved in its unique role within the human gut microbial ecosystem.

SUBMITTER: Dejean G

PROVIDER: S-EPMC8228234 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium Christensenella minuta.

Déjean Guillaume G Tudela Héloïse H Bruno Lisa L Kissi Déborah D Rawadi Georges G Claus Sandrine P SP

Microorganisms 20210609 6

Christensenella minuta are human gut dwelling bacteria that have been proposed as key members of the gut microbiome, regulating energy balance and adiposity of their host. We formerly identified that a novel strain of C. minuta (strain DSM33407) boosted microbiota diversity and stimulated deconjugation of the primary bile acid taurocholic acid in human samples. However, there is no description of a bile salt hydrolase (BSH) protein carried in the genome of C. minuta. Here, w ...[more]

PMID: 34207623

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Project description:The gut bacteria of the family Christensenellaceae are consistently associated with metabolic health, but their role in promoting host health is not fully understood. Here, we explored the effect of Christensenella minuta amendment on voluntary physical activity and the gut microbiome. We inoculated male and female germ-free mice with an obese human donor microbiota together with live or heat-killed C. minuta for 28 days and measured physical activity in respirometry cages. Compared to heat-killed, the live-C. minuta treatment resulted in reduced feed efficiency and higher levels of physical activity, with significantly greater distance traveled for males and higher levels of small movements and resting metabolic rate in females. Sex-specific effects of C. minuta treatment may be in part attributable to different housing conditions for males and females. Amendment with live C. minuta boosted gut microbial biomass in both sexes, immobilizing dietary carbon in the microbiome, and mice with high levels of C. minuta lose more energy in stool. Live C. minuta also reduced within and between-host gut microbial diversity. Overall, our results showed that C. minuta acts as a keystone species: despite low relative abundance, it has a large impact on its ecosystem, from the microbiome to host energy homeostasis.IMPORTANCEThe composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family Christensenellaceae has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live C. minuta influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed C. minuta. Importantly, live C. minuta boosts the biomass of the microbiome in the gut, and a higher level of C. minuta is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the Christensenellaceae can influence host energy homeostasis and health.

Project description:IntroductionGut microbes form complex networks that significantly influence host health and disease treatment. Interventions with the probiotic bacteria on the gut microbiota have been demonstrated to improve host well-being. As a representative of next-generation probiotics, Christensenella minuta (C. minuta) plays a critical role in regulating energy balance and metabolic homeostasis in human bodies, showing potential in treating metabolic disorders and reducing inflammation. However, interactions of C. minuta with the members of the networked gut microbiota have rarely been explored.MethodsIn this study, we investigated the impact of C. minuta on fecal microbiota via metagenomic sequencing, focusing on retrieving bacterial strains and coculture assays of C. minuta with associated microbial partners.ResultsOur results showed that C. minuta intervention significantly reduced the diversity of fecal microorganisms, but specifically enhanced some groups of bacteria, such as Lactobacillaceae. C. minuta selectively enriched bacterial pathways that compensated for its metabolic defects on vitamin B1, B12, serine, and glutamate synthesis. Meanwhile, C. minuta cross-feeds Faecalibacterium prausnitzii and other bacteria via the production of arginine, branched-chain amino acids, fumaric acids and short-chain fatty acids (SCFAs), such as acetic. Both metagenomic data analysis and culture experiments revealed that C. minuta negatively correlated with Klebsiella pneumoniae and 14 other bacterial taxa, while positively correlated with F. prausnitzii. Our results advance our comprehension of C. minuta's in modulating the gut microbial network.ConclusionsC. minuta disrupts the composition of the fecal microbiota. This disturbance is manifested through cross-feeding, nutritional competition, and supplementation of its own metabolic deficiencies, resulting in the specific enrichment or inhibition of the growth of certain bacteria. This study will shed light on the application of C. minuta as a probiotic for effective interventions on gut microbiomes and improvement of host health.

Project description:Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.

Dataset Information

Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium Christensenella minuta.

Publications

Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium <i>Christensenella minuta</i>.

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