Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment

Area of Science:

• Hepatology
• Gastroenterology
• Microbiology
• Mitochondrial Biology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, characterized by complex multifactorial pathology.
• Mitochondrial dysfunction and gut microbiota dysbiosis are key contributors to MASLD pathogenesis.
• Emerging research highlights the critical interplay between gut microbiota and host mitochondria, influencing metabolic health.

Purpose of the Study:

• To review the role of gut microbiota metabolites in MASLD.
• To emphasize the impact of these metabolites on mitochondrial function within the context of MASLD.
• To discuss current and potential therapeutic strategies targeting the gut microbiota for MASLD management.

Main Methods:

• Literature review of studies investigating the gut microbiota, metabolites, and mitochondrial function in MASLD.
• Analysis of the mechanisms by which microbial metabolites influence host mitochondrial physiology.
• Synthesis of information on therapeutic interventions modulating the gut microbiota for MASLD.

Main Results:

• Gut microbiota metabolites are identified as crucial mediators influencing extraintestinal organs, including the liver, in MASLD.
• Specific metabolites significantly impact mitochondrial dysfunction, contributing to key pathological features of MASLD such as steatosis, oxidative stress, inflammation, and fibrosis.
• Restoring gut microbiota balance through various interventions shows promise for improving MASLD.

Conclusions:

• The gut microbiota and its metabolites play a pivotal role in the development and progression of MASLD, particularly through their effects on mitochondrial function.
• Targeting gut microbiota composition and function represents a promising therapeutic avenue for MASLD.
• Further research into microbiota-based therapies like probiotics, prebiotics, and fecal microbiota transplantation is warranted for effective MASLD management.