Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease
Abstract
Objective: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila , a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD. Design: The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A. muciniphila abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of A. muciniphila on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed. Results: Patients with ASH exhibited a decreased abundance of faecal A. muciniphila when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in A. muciniphila abundance. Ethanol-induced intestinal A. muciniphila depletion could be restored by oral A. muciniphila supplementation. Furthermore, A. muciniphila administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. A. muciniphila also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically ameliorated hepatic injury and neutrophil infiltration. Conclusion: Ethanol exposure diminishes intestinal A. muciniphila abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. A. muciniphila promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from A. muciniphila supplementation.
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Akkermansia muciniphila is beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes.
“Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia and has been shown to be beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes (Grander et al., 2018; Qin et al., 2012).”
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 Grander et al., 2018
Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia.
“Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia and has been shown to be beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes (Grander et al., 2018; Qin et al., 2012).”
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 Grander et al., 2018
Probiotics such as Lactobacillus, Bifidobacterium, and Ackermannia may enhance intestinal integrity through various mechanisms, normalizing intestinal cytokine levels, balancing intestinal immunity, and reducing inflammation.
“Probiotics such as Lactobacillus, Bifidobacterium, and Ackermannia may enhance intestinal integrity through a variety of mechanisms [21–24], normalizing intestinal cytokine levels, balancing intestinal immunity, and reducing inflammation.”
The role of mucins during liver disease remains controversial as mucin deficiency protects from alcohol induced hepatitis in mice, while enhanced mucus thickness relates to improved liver function in another study of experimental ALD.
“Interestingly, the role of mucins (the glycoproteins that compose the mucus) during liver disease remains controversial as mucin deficiency protects from alcohol induced hepatitis in mice32, while enhanced mucus thickness relates to improved liver function in other study of experimental ALD33.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [33]
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Therapeutic Targeting of Myeloperoxidase Attenuates NASH in Mice
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- Authors
- Grander, C., Adolph, T. E., Wieser, V., Lowe, P., Wrzosek, L., Gyongyosi, B., Ward, D. V., Grabherr, F., Gerner, R. R., Pfister, A., Enrich, B., Ciocan, D., Macheiner, S., Mayr, L., Drach, M., Moser, P., Moschen, A. R., Perlemuter, G., Szabo, G., Cassard, A. M., & Tilg, H.
- Affiliations
- Innsbruck Medical University (AT)
- University of Massachusetts Chan Medical School (US)
- Inserm (FR)
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
- University Hospital Zurich (CH)
- Corresponding author
- Tilg, Herbert
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-05-26
- Volume
- 67
- Issue
- 5
- Pages
- 891-901
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2619680342
- Cited by
- 618
- References
- 58
- Citations by year
- 2026: 47 · 2025: 58 · 2024: 88 · 2023: 82 · 2022: 90 · 2021: 77 · 2020: 86 · 2019: 44 · 2018: 36 · 2017: 10
- FWCI
- 19.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-LABX-0033)
- National Institute on Alcohol Abuse and Alcoholism (R01AA017729)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Akkermansia muciniphila, alcoholic liver disease, alcoholic steatohepatitis, intestinal barrier integrity, leaky gut, mucus production, tight junctions, neutrophil infiltration, hepatic steatosis
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Ethanol, Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Feces, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Liver, Liver Diseases, Alcoholic, Male, Mice, Inbred C57BL, Middle Aged, Mice, Verrucomicrobia
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