Dataset Information

Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice.

ABSTRACT: Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptin ^db/db mice for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and reduced glucose output. We also found that CB0313.1 modulated gut microbiota composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes, reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased butyrate-producing bacteria. Changes in gut microbiota following CB0313.1 treatment were associated with enhanced peroxisome proliferator-activated receptor-? (PPAR?), insulin signaling molecules and mitochondrial function markers. Together, our study suggests that CB0313.1 may act as a beneficial probiotic for the prevention and treatment of hyperglycemia and associated metabolic dysfunction.

SUBMITTER: Jia L

PROVIDER: S-EPMC5539151 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice.

Jia Lingling L Li Dongyao D Feng Ninghan N Shamoon Muhammad M Sun Zhenghua Z Ding Lei L Zhang Hao H Chen Wei W Sun Jia J Chen Yong Q YQ

Scientific reports 20170801 1

Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptin <sup>db/db</sup> mice for 5 weeks ...[more]

PMID: 28765642

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Project description:Clostridium butyricum, the type species of the genus Clostridium, is considered an obligate anaerobe, yet it has been shown to grow in the presence of oxygen. C. butyricum strains atypically producing the botulinum neurotoxin type E are the leading cause of type E human botulism in Italy. Here, we show that type E botulinum neurotoxin-producing C. butyricum strains growing exponentially were able to keep growing and producing toxin in vitro upon exposure to air, although less efficiently than under ideal oxygen-depleted conditions. Bacterial growth in air was maintained when the initial cell density was higher than 103 cells/ml. No spores were detected in the cultures aerated for 5 h. To understand the biological mechanisms allowing the adaptation of vegetative cells of C. butyricum type E to oxygen, we compared the proteome and metabolome profiles of the clostridial cultures grown for 5 h under either aerated or anaerobic conditions. The results indicated that bacterial cells responded to oxygen stress by slowing growth and modulating the expression of proteins involved in carbohydrate uptake and metabolism, redox homeostasis, DNA damage response, and bacterial motility. Moreover, the ratio of acetate to butyrate was significantly higher under aeration. This study demonstrates for the first time that a botulinum neurotoxin-producing Clostridium can withstand oxygen during vegetative growth. IMPORTANCE Botulinum neurotoxins, the causative agents of the potentially fatal disease of botulism, are produced by certain Clostridium strains during vegetative growth, usually in anaerobic environments. Our findings indicate that, contrary to current understanding, the growth of neurotoxigenic C. butyricum strains and botulinum neurotoxin type E production can continue upon transfer from anaerobic to aerated conditions and that adaptation of strains to oxygenated environments requires global changes in proteomic and metabolic profiles. We hypothesize that aerotolerance might constitute an unappreciated factor conferring physiological advantages on some botulinum toxin-producing clostridial strains, allowing them to adapt to otherwise restrictive environments.

Project description:The human gut is colonized by a complex microbiota with multiple benefits. Although the surface-attached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease.

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Dataset Information

Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice.

Publications

Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice.

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