Dataset Information

L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota.

ABSTRACT: A previously unknown metabolic pathway for the utilization of l-galactose was discovered in a prevalent gut bacterium, Bacteroides vulgatus. The new pathway consists of three previously uncharacterized enzymes that were found to be responsible for the conversion of l-galactose to d-tagaturonate. Bvu0219 (l-galactose dehydrogenase) was determined to oxidize l-galactose to l-galactono-1,5-lactone with kcat and kcat/Km values of 21 s(-1) and 2.0 × 10(5) M(-1) s(-1), respectively. The kinetic product of Bvu0219 is rapidly converted nonenzymatically to the thermodynamically more stable l-galactono-1,4-lactone. Bvu0220 (l-galactono-1,5-lactonase) hydrolyzes both the kinetic and thermodynamic products of Bvu0219 to l-galactonate. However, l-galactono-1,5-lactone is estimated to be hydrolyzed 300-fold faster than its thermodynamically more stable counterpart, l-galactono-1,4-lactone. In the final step of this pathway, Bvu0222 (l-galactonate dehydrogenase) oxidizes l-galactonate to d-tagaturonate with kcat and kcat/Km values of 0.6 s(-1) and 1.7 × 10(4) M(-1) s(-1), respectively. In the reverse direction, d-tagaturonate is reduced to l-galactonate with values of kcat and kcat/Km of 90 s(-1) and 1.6 × 10(5) M(-1) s(-1), respectively. d-Tagaturonate is subsequently converted to d-glyceraldehyde and pyruvate through enzymes encoded within the degradation pathway for d-glucuronate and d-galacturonate.

SUBMITTER: Hobbs ME

PROVIDER: S-EPMC4108180 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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l-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota.

Hobbs Merlin Eric ME Williams Howard J HJ Hillerich Brandan B Almo Steven C SC Raushel Frank M FM

Biochemistry 20140707 28

A previously unknown metabolic pathway for the utilization of l-galactose was discovered in a prevalent gut bacterium, Bacteroides vulgatus. The new pathway consists of three previously uncharacterized enzymes that were found to be responsible for the conversion of l-galactose to d-tagaturonate. Bvu0219 (l-galactose dehydrogenase) was determined to oxidize l-galactose to l-galactono-1,5-lactone with kcat and kcat/Km values of 21 s(-1) and 2.0 × 10(5) M(-1) s(-1), respectively. The kinetic produc ...[more]

PMID: 24963813

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Project description:Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a prevalent mutualist across human populations and confers multiple health benefits such as immunoregulation, antiobesity, and coronary artery disease intervention. However, its role in antihyperlipidemia has not been systematically characterized. This study sought to identify the effect of B. vulgatus Bv46 on hyperlipidemia. Hyperlipidemic rats were modeled by feeding them a high-fat diet for 6 weeks. The effect of B. vulgatus Bv46 supplementation was evaluated by measuring anthropometric parameters, lipid and inflammation markers, and the liver pathology. Multi-omics was used to explore the underlying mechanisms. The ability of B. vulgatus Bv46 to produce bile salt hydrolase was confirmed by gene annotation and in vitro experiments. Oral administration of B. vulgatus Bv46 in hyperlipidemic rats significantly reduced the body weight gain, food efficiency, and liver index, improved the serum lipid profile, lowered the levels of serum inflammatory cytokines, promoted the loss of fecal bile acids (BAs), and extended the fecal pool of short-chain fatty acids (SCFAs), especially propionate and butyrate. B. vulgatus Bv46 induced compositional shifts of the gut microbial community of hyperlipidemic rats, characterized by a lower ratio of Firmicutes to Bacteroidetes with an increase of genera Bacteroides and Parabacteroides. After intervention, serum metabolite profiling exhibited an adaptation in amino acids and glycerophospholipid metabolism. Transcriptomics further detected altered biological processes, including primary bile acid biosynthesis and fatty acid metabolic process. Taken together, the findings suggest that B. vulgatus Bv46 could be a promising candidate for interventions against hyperlipidemia. IMPORTANCE As a core microbe of the human gut ecosystem, Bacteroides vulgatus has been linked to multiple aspects of metabolic disorders in a collection of associative studies, which, while indicative, warrants more direct experimental evidence to verify. In this study, we experimentally demonstrated that oral administration of B. vulgatus Bv46 ameliorated the serum lipid profile and systemic inflammation of high-fat diet-induced hyperlipidemic rats in a microbiome-regulated manner, which appears to be associated with changes of bile acid metabolism, short-chain fatty acid biosynthesis, and serum metabolomic profile. This finding supports the causal contribution of B. vulgatus in host metabolism and helps to form the basis of novel therapies for the treatment of hyperlipidemia.

Project description:The Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has significant clinical potential for patients with acute liver failure (ALF). However, the experimental evidence of the effect of QCLGF on ALF and the associated mechanisms remain elusive. We aimed to evaluate the function of QCLGF in ALF and the underlying mechanism. ALF was induced in rats by intraperitoneal injection of D-GalN (1100 mg/kg). The Qingchangligan formula was administered to the rats (6.725 g/kg · d) for 5 days, and the model group and the control group were given the same amount of physiological saline. Then 16S rRNA gene sequencing, high performance gas chromatography-mass spectrometry (GC-MS), and RNA-seq analysis were performed on the samples. The levels of ALT and AST in the ALF rats were abnormal (5322.08 ± 566.27 U/L and 7655.95 ± 1238.08 U/L, respectively) compared with the normal control (98.98 ± 6.90 U/L and 99.63 ± 10.94 U/L, respectively). The levels of ALT and AST in the QCLGF rats (2997.67 ± 469.24 U/L and 4158.40 ± 596.07 U/L, respectively) were closer the normal control group. Liver HE staining showed that the degree of liver damage in the QCLGF rats was lighter than that in the ALF rats. The overall structure of the gut microbiota after ALF was significantly altered, including Proteobacteria, Blautia, Romboutsia, Parabacteroides, UCG-008, Parasutterella, Ruminococcus, norank_f:Lachnospiraceae, the Eubacterium_xylanophilum_group, Oscillibacter, and Eisenbergiella. QCLGF balanced the structure and abundance of intestinal flora. The levels of D(+)galactose, isopropyl beta-D-1-thiogalactopyranoside and D-mannitol were lighter in the plasma of the ALF rats than in the normal control rats, but there were significantly elevated levels of those metabolites in the QCLGF rats. The gene expression changed significantly in the ALF rats. QCLGF regulated the expression of THBS1 and the KEGG pathways of carbohydrate metabolism, lipid metabolism, signal transduction, the immune system, and infectious disease: bacterial. QCLGF may alleviating intestinal flora disorder, regulating galactose metabolism and downregulating the expression of THBS1 to alleviate D-GalN induced acute liver failure.

Dataset Information

L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota.

Publications

l-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota.

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