Cited by 420Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesProbiotics and Fermented Foods

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Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems

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Xu, Yu, Wang, Ning, Tan, Hor-Yue, Li, Sha, Zhang, Cheng, Feng, Yibin·2020·Frontiers in Microbiology

DOI 10.3389/fmicb.2020.00219PMC PMC7046546

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Abstract

Obesity and its metabolic syndrome, including liver disorders and type 2 diabetes, are a worldwide epidemic and intimately linked to diet. The gut microbiota interaction has been pointed out as a hot topic research at treating obesity and related metabolic diseases by influencing energy metabolism and immune system. In terms of the novel identified beneficial microbes, Akkermansia muciniphila (A.muciniphila ) is colonized in the mucosa layer of the gut and modulates basal metabolism. A.muciniphila is consistently correlated with obesity. The causal beneficial impact on A.muciniphila-treated obesity is coming to light, which is proved by a variety of animal models and human studies. A.muciniphila has been characterized as a beneficial player in body metabolism and create a great expectation for treatments of the metabolic disorders associated with obesity, as well as considered as new generation therapeutic agents. This paper aimed to was to investigate the underlying basic mechanism of A.muciniphila-related obesity and host interactions in recent discoveries, facilitating to establish the causal relationship in human and the A.muciniphila-associated therapeutic supplement.

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FIGURE 1 Molecular modulation of A. muciniphila in lipid and liver disorder: in yellow are the circulation mechanisms of A. muciniphila in hyperlipidemia and liver disorder. In green are the metabolite mechanisms of A. muciniphila in lipid metabolism in tissue and atherosclerosis.CC BY · PubMed Central

FIGURE 2 Cross talk in host-A. muciniphila interactions and the associated improvement in obesity disease. After the colonization of A. muciniphila, the state of homeostasis and symbiotic relationships is improved by immunity activity. This state includes obesity and its associated liver disorder changes in the host; the gut barrier is restored either physically (at the mucous layer or the level of tight junctions) or at the level of the gut ecosystem, and reduced inflammatory responses are often induced by endotoxemia or LPS via TLRs and downstream cytokines, which improve intestinal permeability. TG, total triglyceride; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; LPS, lipopolysaccharide; TLR, Toll-like receptors; IFNγ, Interferon-γ; TNF, tumor necrosis factor, IL-2, interleukin-2.CC BY · PubMed Central

FIGURE 3 Mechanisms of signaling due to A. muciniphila action in obesity. A. muciniphila can decrease the serum level of inflammatory cytokines such as IL-2, IFN-γ, IL-12p40, and MCP-1. Meanwhile, A. muciniphila decreases the lipid overload process associated with the LDL receptor pathway by decreasing apoB48 and apoB100 on LDLs. Moreover, short-chain fatty acid production stimulated by A. muciniphila is involved in signaling to the host by inhibiting histone deacetylase (HDAC) or by activating G-protein-coupled receptors, which triggers other metabolic pathways, together resulting in immune stimulation including macrophage transmigration and Treg proliferation changes. A. muciniphila regulates the intestinal permeability and gut barrier by tight-junction proteins such as Claudin 3 (Cldn3), Occludi(Ocln), and Cannabinoid Receptor 1 (Cnr1) and reverses the high enzyme expression of flavin-containing monooxygenase 3 (FMO3), which modulates TMA conversion into TMAO in the liver.CC BY · PubMed Central

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Authors: Xu, Y., Wang, N., Tan, H.-Y., Li, S., Zhang, C., & Feng, Y.
Affiliations: University of Hong Kong (HK)
Corresponding author: Feng, Yibin
ORCID: Xu, Yu
Wang, Ning
Tan, Hor-Yue
Li, Sha
Zhang, Cheng
Feng, Yibin
Venue: Frontiers in Microbiology
Publisher: Frontiers Media SA
Published: 2020-02-21
Volume: 11
Pages: 219-219
ISSN: 1664-302X (ISSN-L)
DOI: 10.3389/fmicb.2020.00219
PMC: PMC7046546
OpenAlex: W3008005014
Cited by: 420
References: 112
Citations by year: 2026: 32 · 2025: 56 · 2024: 61 · 2023: 74 · 2022: 106 · 2021: 66 · 2020: 25
FWCI: 6.49
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Microbiology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
The HKU Scholars Hub (University of Hong Kong) (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: University of Hong Kong (104003919, 104004092, 200007008)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords: Akkermansia muciniphila, obesity, gut microbiota, lipid metabolism, immune response, metabolic syndrome, type 2 diabetes, liver disease, mucosa, energy metabolism, probiotic therapy, host-microbe interactions

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Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems

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