Project description:Christensenella minuta was first formally described in 2012 as a member of a novel species, genus, and proposed family of Christensenellaceae. C. minuta was later shown in one study to be part of the most heritable taxonomic group in the human gut microbiome and to be enriched in people with low body mass index (BMI). Mouse work demonstrated that injection of cultured C. minuta into germ-free mice prevented the onset of obesity after a fecal transplant to the mice from high BMI individuals. Here we describe the genome sequence of C. minuta DSM 22607. Examination and analysis of the annotation revealed an unusually high number of genes predicted to be involved in carbohydrate metabolism, many of which were multiple homologs of RbsA, RbsB and RbsC, which together make up the Ribose ABC Transport System. These genes may be also involved in quorum sensing which could potentially relate to the importance of C. minuta in the gut microbiome.
Project description:Obesity is associated with gut microbiota dysbiosis, characterized by a high Firmicutes/Bacteroidetes ratio. Gut-dwelling bacteria of the Christensenellaceae family have been proposed to act as keystones of the human gut ecosystem and to prevent adipogenesis. The objectives of the present study were to demonstrate the antiobesity potential of a new strain of Christensenella minuta in preclinical models and explore related mechanisms of action. The antiobesity potential of C. minuta DSM33407 was assessed in a diet-induced obesity mouse model. Changes in hepatic lipid metabolism were explored using targeted transcriptomics. Effects on gut microbiota were further assessed in a humanized Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model inoculated with obese fecal samples. Shotgun metagenomics was applied to study microbial community structures in both models. C. minuta DSM33407 protected from diet-induced obesity and regulated associated metabolic markers such as glycemia and leptin. It also regulated hepatic lipid metabolism through a strong inhibition of de novo lipogenesis and maintained gut epithelial integrity. In the humanized SHIME® model, these effects were associated with modulations of the intestinal microbiota characterized by a decreased Firmicutes/Bacteroidetes ratio. These data indicate that C. minuta DSM33407 is a convincing therapeutic candidate for the management of obesity and associated metabolic disorders.
Project description: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.
Project description:D-allulose, which is one of the important rare sugars, has gained significant attention in the food and pharmaceutical industries as a potential alternative to sucrose and fructose. Enzymes belonging to the D-tagatose 3-epimerase (DTEase) family can reversibly catalyze the epimerization of D-fructose at the C3 position and convert it into D-allulose by a good number of naturally occurring microorganisms. However, microbial synthesis of D-allulose is still at its immature stage in the industrial arena, mostly due to the preference of slightly acidic conditions for Izumoring reactions. Discovery of novel DTEase that works at acidic conditions is highly preferred for industrial applications. In this study, a novel DTEase, DTE-CM, capable of catalyzing D-fructose into D-allulose was applications. In this study, a novel DTEase, DTE-CM, capable of catalyzing D-fructose into D-allulose was DTE-CM on D-fructose was found to be remarkably influenced and modulated by the type of metal ions (co-factors). The DTE-CM on D-fructose was found to be remarkably influenced and modulated by the type of metal ions (co-factors). The 50°C from 0.5 to 3.5 h at a concentration of 0.1 mM. The enzyme exhibited its maximum catalytic activity on D-fructose at pH 6.0 and 50°C from 0.5 to 3.5 h at a concentration of 0.1 mM. The enzyme exhibited its maximum catalytic activity on -fructose at pH 6.0 and 50°C with a K cat /K m value of 45 mM-1min-1. The 500 g/L D-fructose, which corresponded to 30% conversion rate. With these interesting catalytic properties, this enzyme could be a promising candidate for industrial biocatalytic applications.