Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis
Open accessAbstract
The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut–liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD.
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Recent research found that A. muciniphila increases mitochondrial oxidation and bile acid metabolism in the gut-liver axis, leading to the reshaping of gut microbiota.
“Recent research found that A. muciniphila increases mitochondrial oxidation and bile acid metabolism in the gut–liver axis, leading to the reshaping of gut microbiota (Rao et al., 2021).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Rao et al., 2021
The Results report increased mitochondrial markers and lipid-oxidation activity in treated mice, along with changes consistent with improved bile acid metabolism in the gut–liver axis. The Discussion says enhanced bile acid metabolism *might* help remodel gut microbiota composition; it does not establish that the observed changes led to microbiota reshaping. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Rao, Y., Kuang, Z., Li, C., Guo, S., Xu, Y., Zhao, D., Hu, Y., Song, B., Jiang, Z., Ge, Z., Liu, X., Li, C., Chen, S., Ye, J., Huang, Z., & Lu, Y.
- Affiliations
- Sun Yat-sen University (CN)
- Sun Yat-sen University
- RMIT University
- Corresponding author
- Rao, Yong
- Lu, Yongjun
- ORCID
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2021-01-01
- Volume
- 13
- Issue
- 1
- Pages
- 1-19
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC8158032
- OpenAlex
- W3165210923
- Cited by
- 356
- References
- 70
- Citations by year
- 2026: 65 · 2025: 112 · 2024: 67 · 2023: 51 · 2022: 46 · 2021: 14 · 2017: 1
- FWCI
- 13.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion)
- Funders
- National Natural Science Foundation of China (81930098 to ZSH, 21672265 and 81872732 to ZSH, 81703336 to YR)
- Science and Technology Program of Guangzhou (201704020104 to ZSH)
- Science and Technology Development in Guangdong Province (2016A020217004 to ZSH)
- Natural Science Foundation of Guangdong Province (2017A030308003 to ZSH)
- Guang Dong Cheung Kong Philanthropy Foundation to YJL
- Fundamental Research Funds for the Central Universities
- Guang Dong Cheung Kong Philanthropy Foundation
- Outstanding Talents of Guangdong Special Plan (2019JC05Y456)
- the Science and Technology Program of Guangzhou (201704020104)
- Special Fund for Science and Technology Development in Guangdong Province (2016A020217004)
- the Natural Science Foundation of Guangdong Province (2017A030308003)
- Guangdong key areas R & D projects (2018B020205002)
- Key projects of National Natural Science Foundation of China (81930098)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- Akkermansia muciniphila, non-alcoholic fatty liver disease, L-aspartic acid, gut-liver axis, bile acid metabolism, hepatic steatosis, oxidative stress, apoptosis, gut microbiota, high-fat high-cholesterol diet, obesity, mitochondrial oxidation, antibiotic-treated mice
- MeSH terms
- Gastrointestinal Microbiome, Akkermansia, Animals, Aspartic Acid, Bacteria, Fatty Liver, Humans, Liver, Male, Mice, Inbred C57BL, Gastrointestinal Tract, Mice, Diet, High-Fat
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