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Engineered Akkermansia muciniphila: A promising agent against diseases (Review).

ABSTRACT: Achieving a harmonious gut microbial ecosystem has been hypothesized to be a successful method for alleviating metabolic disorders. The administration of probiotics, such as Lactobacillus and Bifidobacteria, is a known traditional and safe pathway to regulate human commensal microbes. With advancements in genetic sequencing and genetic editing tools, more bacteria are able to function as engineered probiotics with multiple therapeutic properties. As one of the next-generation probiotic candidates, Akkermansia muciniphila (A. muciniphila) has been discovered to enhance the gut barrier function and moderate inflammatory responses, exhibit improved effects with pasteurization and display beneficial probiotic effects in individuals with obesity, type 2 diabetes, atherosclerosis and autism-related gastrointestinal disturbances. In view of this knowledge, the present review aimed to summarize the effects of A. muciniphila in the treatment of metabolic disorders and to discuss several mature recombination systems for the genetic modification of A. muciniphila. From gaining an enhanced understanding of its genetic background, ingested A. muciniphila is expected to be used in various applications, including as a diagnostic tool, and in the site-specific delivery of therapeutic drugs.

SUBMITTER: Zou Y

PROVIDER: S-EPMC7668130 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Engineered Akkermansia muciniphila: A promising agent against diseases (Review).

Zou Yixuan Y Chen Tingtao T

Experimental and therapeutic medicine 20201029 6

Achieving a harmonious gut microbial ecosystem has been hypothesized to be a successful method for alleviating metabolic disorders. The administration of probiotics, such as Lactobacillus and Bifidobacteria, is a known traditional and safe pathway to regulate human commensal microbes. With advancements in genetic sequencing and genetic editing tools, more bacteria are able to function as engineered probiotics with multiple therapeutic properties. As one of the next-generation probi ...[more]

PMID: 33209129

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Project description:Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7-8 per group) and continuously administrated A. muciniphila MucT or PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota analysis on the 15th day, and acute liver injury was induced by Concanavalin A (Con A, 15 mg/kg) injection through the tail vein. Samples (blood, liver, ileum, colon) were assessed for liver injury, systemic inflammation, and intestinal barrier function. We found that oral administration of A. muciniphila decreased serum ALT and AST and alleviated liver histopathological damage induced by Con A. Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-γ, IL-12p40, MCP-1, MIP-1a, MIP-1b) were substantially attenuated. A. muciniphila significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence analysis indicated that A. muciniphila increased microbial richness and diversity. The community structure of the Akk group clustered distinctly from that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and Bacteroidetes abundance decreased. Correlation analysis showed that injury-related factors (IL-12p40, IFN-γ, DR5) were negatively associated with specific genera (Ruminococcaceae_UCG_009, Lachnospiraceae_UCG_001, Akkermansia), which were enriched in mice pretreated with A. muciniphila. Our results suggested that A. muciniphila MucT had beneficial effects on immune-mediated liver injury by alleviating inflammation and hepatocellular death. These effects may be driven by the protective profile of the intestinal community induced by the bacteria. The results provide a new perspective on the immune function of gut microbiota in host diseases.

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Engineered Akkermansia muciniphila: A promising agent against diseases (Review).

Publications

Engineered <i>Akkermansia muciniphila</i>: A promising agent against diseases (Review).

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