Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the adult population in high-income countries and has become a leading indication for liver transplantation. NAFLD can progress to more severe conditions such as hepatocellular carcinoma. The gut microbiota dysbiosis has been firmly established as a contributing factor to NAFLD. In this study, we investigate the association between gut microbiota composition and NAFLD severity, focusing on the depletion of Adlercreutzia equolifaciens in patients with liver diseases. We explore the potential anti-inflammatory properties of A. equolifaciens as a therapeutic strategy for liver diseases.
Methods
- Participants: The study included patients with liver diseases such as NAFLD/NASH, along with healthy controls for comparison.
- Gut Microbiota Analysis: Shotgun metagenomic sequencing was performed to analyze the composition of the gut microbiota in patients and healthy controls.
- Identification of A. equolifaciens: The presence and abundance of A. equolifaciens in the gut microbiota were determined through genomic analysis.
- In vitro Studies: In vitro experiments were conducted to assess the anti-inflammatory properties of A. equolifaciens on human intestinal epithelial cells and hepatocytes. The NF-ΞΊB pathway was examined as a key inflammatory pathway.
- In vivo Mouse Model: A humanized mouse model of NAFLD was utilized to evaluate the effects of A. equolifaciens on weight gain, glycemia, and inflammatory markers. PCR analysis of fecal microbiota was performed to monitor the persistence of A. equolifaciens in the mouse gut.
Key Scientific Findings
Decreased Abundance of A. equolifaciens in NAFLD/NASH Patients:
- A. equolifaciens is depleted in patients with liver diseases such as NAFLD/NASH compared to healthy controls.
- The abundance of A. equolifaciens decreases as the disease progresses, suggesting a strong association with disease severity.
- Similar to other key protective bacteria in different pathologies, such as Faecalibacterium prauznitzii and Akkermancia muciniphila, A. equolifaciens plays a crucial protective role in maintaining gut health.
A. equolifaciens Presence in Human Gut:
- Genomic analysis reveals that A. equolifaciens strains are closely related, and the existence of subspecies is not supported by extensive genome comparison.
- While originally named for its equol production capacity, most strains of A. equolifaciens lack the equol production pathway, suggesting other metabolic functionalities may be significant.
- A. equolifaciens is depleted not only in liver diseases but also in other pathologies, including ulcerative colitis.
A. equolifaciens Presents Anti-Inflammatory Properties:
- In vitro experiments demonstrate that A. equolifaciens possesses anti-inflammatory properties by inhibiting the NF-ΞΊB pathway in intestinal epithelial cells and hepatocytes.
- The anti-inflammatory effect is not attributed to short-chain fatty acid production, as A. equolifaciens does not produce butyrate or propionate.
- In vivo mouse experiments show reduced weight gain and improved glycemia in mice administered A. equolifaciens, accompanied by lower expression of inflammatory markers.
A. equolifaciens exhibits promising anti-inflammatory properties in vitro and in vivo, suggesting its potential as a therapeutic candidate for liver diseases such as NAFLD/NASH. Further research is warranted to explore its mechanisms of action and assess its efficacy in clinical settings. A. equolifaciens may also have implications for other diseases, highlighting its role as a key commensal bacterium in maintaining gut and metabolic health.
Link to the article : https://tinyurl.com/48phsb73
