Health and Disease: Akkermansia muciniphila, the Shining Star of the Gut Flora

Abstract

Akkermansia muciniphila (A. muciniphila) has drawn much attention as an important gut microbe strain in recent years. A. muciniphila can influence the occurrence and development of diseases of the endocrine, nervous, digestive, musculoskeletal, and respiratory systems and other diseases. It can also improve immunotherapy for some cancers. A. muciniphila is expected to become a new probiotic in addition to Lactobacillus and Bifidobacterium. An increase in A. muciniphila abundance through direct or indirect A. muciniphila supplementation may inhibit or even reverse disease progression. However, some contrary findings are found in type 2 diabetes mellitus and neurodegenerative diseases, where increased A. muciniphila abundance may aggravate the diseases. To enable a more comprehensive understanding of the role of A. muciniphila in diseases, we summarize the relevant information on A. muciniphila in different systemic diseases and introduce regulators of A. muciniphila abundance to promote the clinical transformation of A. muciniphila research.

Fig. 1.

Changes in A. muciniphila abundance and regulators of A. muciniphila. Abnormal abundance of A. muciniphila can occur in the endocrine, nervous, digestive, respiratory, and motor systems. Under the influence of various factors, A. muciniphila abundance changes and affects the progression of these diseases.

Fig. 2.

The regulatory mechanism of A. muciniphila in obesity. Amuc_1100 promotes p-Akt^thr and Akt^ser expression to enhance insulin sensitivity. Amuc_1100 improves intestinal permeability activation by regulating Cldn3 expression and the Cnr1/CB1 axis in vivo. Cldn3 expression regulated by Amuc_1100 also contributes to the improvement of intestinal permeability. P9 recognizes and binds to the ligand ICAM-2. P9 then induces GLP-1 secretion by promoting p-CREB and p-HSP27 expression levels. P9 promotes thermogenesis and improves obesity and glucose homeostasis in high-fat diet-fed mice by activating the GLP-1R signaling pathway and IL-6. A. muciniphila administration inhibits adipogenesis in adipocytes via the SERPINA3/CTSB axis. It also increases 2-pg and 1-pg levels in circulating blood and activates peroxisome proliferator-activated receptor alpha (PPARα) to regulate lipid metabolism. A. muciniphila reduces carbohydrate absorption by reducing GLUT2, GLUT5, and SGLT1 expression. A. muciniphila reduces the expression levels of the hepatic lipogenesis markers SREBP-1c, ACC, and FAS.

Fig. 3.

Fig. 4.

The regulatory role of A. muciniphila in neoplastic disease. Amuc_1434 induces G0/G1 cell cycle arrest by promoting p53 expression in colorectal cancer. Amuc_1434 inhibits the proliferation of LS174T cells through regulation of Muc2. Amuc_1434 activates death receptors and mitochondrial apoptosis pathways to promote apoptosis in LS174T cells. In colorectal cancer, A. muciniphila induces M1-like macrophage polarization by regulating the TLR2/NLRP3 and NF-κB pathways; activated NLRP3 in Kupffer cells promotes the recruitment of NK cells to kill tumor cells. A. muciniphila extracellular vesicles enhance the anti-prostate cancer immune response of cytotoxic T lymphocytes by increasing the proportion of GZMB⁺CD8⁺ T cells and IFNγ⁺CD8⁺ T cells.