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Whole Genome Sequence of SNUG61027 Akkermansia muciniphila

ABSTRACT: Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice

PROVIDER: PRJEB42664 | ENA |

REPOSITORIES: ENA

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Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease

Project description:The gut microbiome is a key factor regulating energy-metabolism, glucose tolerance and the immune system. Akkermansia muciniphila has been identified as being beneficial gut bacterium for metabolic diseases, including obesity and type 2 diabetes (T2D); however, the molecular mechanisms involved in host interactions have yet to be known. Here, we described the effects of A. muciniphila on thermogenesis and GLP-1 secretion through the specific secretory protein produced by A. muciniphila and its mode of action. A. muciniphila significantly elevated thermogenesis with induction of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and systemic glucagon-like peptide-1 (GLP-1) secretion. Using fast protein liquid chromatography (FPLC) and liquid chromatography (LC)-mass spectrophotometry (MS)/MS analysis, we discovered that a novel 84-kDa protein, P9 is secreted by A. muciniphila and this protein improves obesity and glucose tolerance by inducing GLP-1 secretion and BAT thermogenesis. P9 induces GLP-1 secretion with direct interaction with the specific host protein, intercellular adhesion molecule-2 (ICAM-2), via IL-6 dependent pathway. This novel host-microbe interaction between P9 and ICAM-2 may become a therapeutic target for metabolic diseases.

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Project description:Akkermansia muciniphila is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of A. muciniphila in regulating intestinal homeostasis remain to be explored. Here, we discovered that A. muciniphila was dramatically increased during colitis recovery, and its colonization greatly increased goblet cells to protect the intestinal barrier in mice. Amuc_0904, a previously uncharacterized A. muciniphila outer membrane protein, was identified to induce goblet cell differentiation.We want to find the receptors that 904 interacts with cells to explore the detailed mechanism.

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Project description:Akkermansia muciniphila, a common member of the human gut microbiota, is considered to be a beneficial resident of the intestinal mucus layer. Surface-exposed molecules produced by this organism likely play important roles in colonization and communication with other microbes and the host, but the protein composition of the outer membrane has not been characterized thus far. Herein we identify A. muciniphila proteins after enrichment and fractionation of the outer membrane proteome of A. muciniphila.

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