Utilizing the gut microbiome as a therapeutic target for liver disease – Narrative review

Liver diseases pose a significant burden on public health worldwide, with chronic liver disease accounting for over 50,000 deaths annually in the USA alone. Chronic liver disease involves persistent inflammation, destruction, and regeneration of liver tissue, with various etiologies such as nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), hepatitis, hepatotoxicity, and autoimmune disease. Recent research has underscored the pivotal role of the gut microbiome in liver health and disease progression. This review delves into the intricate interplay between the gut microbiome and the liver, highlighting key mechanisms and exploring potential therapeutic strategies targeting the gut microbiome for liver disease management.

Gut Microbiome and Liver Disease Progression
The gut microbiome, comprising a diverse array of microorganisms, plays a vital role in maintaining digestive health and immune homeostasis. Dysbiosis, an imbalance in the gut microbial community, can disrupt these functions, leading to a leaky gut barrier and translocation of bacterial products into the liver. This, in turn, triggers inflammatory responses and contributes to liver disease progression. Bile acids (BAs), modulated by gut microbiota, also play a crucial role in antibacterial and immune defenses. Dysbiosis impacts BA regulation through the farnesoid X receptor (FXR), further exacerbating liver disease.

Elements of Gut Microbiome Contributing to Liver Disease
The composition of the gut microbiome is influenced by multiple factors, including diet, lifestyle, and microbial agents. Variations in microbial populations serve as markers of liver disease and offer insight into disease progression. For instance, NAFLD patients exhibit decreased Bacteroidetes and increased Prevotella and Porphyromonas, while cirrhotic patients often show an increase in Enterobacteriaceae and Enterococcus. These changes highlight the potential for microbiome-targeted therapies in restoring balance and mitigating liver damage.

Prebiotics and Probiotics: Therapeutic Approaches
Prebiotics and probiotics, individually or in combination (synbiotics), represent promising therapeutic strategies for liver disease. Probiotics, consisting of live, nonpathogenic microorganisms, can restore gut microbiome balance. Prebiotics, on the other hand, are substrates that selectively stimulate the growth and/or activity of beneficial gut bacteria.

1. Probiotics: Clinical studies have demonstrated the efficacy of probiotics in treating various liver conditions, including minimal hepatic encephalopathy (MHE) and NAFLD. A study on MHE patients found that probiotics, either alone or in combination with lactulose, improved symptoms. Similarly, a prospective trial on NAFLD patients showed that lifestyle modifications coupled with probiotic supplementation significantly improved NAFLD activity score, inflammation, and fibrosis.
2. Prebiotics: Although research on prebiotics in liver disease is less extensive, they have shown potential in improving gut barrier function, host immunity, and reducing pathogenic subpopulations.

Fecal Microbiota Transplantation (FMT)
FMT, an innovative therapy involving the transplantation of gut microbiota from a healthy donor into a recipient, has emerged as a promising treatment option for liver diseases refractory to standard treatments. FMT has shown success in restoring gut microbiome balance and alleviating symptoms in various liver diseases, including NASH and cirrhosis. However, further research is needed to establish its long-term safety and efficacy.

Conclusions
The gut microbiome is intricately linked to liver health and disease progression. Dysbiosis can contribute to liver damage by disrupting gut barrier function and promoting inflammatory responses. Prebiotics, probiotics, and FMT represent promising therapeutic strategies that aim to restore gut microbiome balance and mitigate liver disease. Further research is essential to optimize these therapies and explore their potential in various liver disease etiologies. By targeting the gut microbiome, we may unlock new avenues for managing and treating liver diseases, ultimately improving patient outcomes.

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https://www.xiahepublishing.com/2994-8754/JTG-2023-00027

The study was recently published in the Journal of Translational Gastroenterology.

Journal of Translational Gastroenterology (JTG) dedicates to improving clinical diagnosis and treatment, advancing understanding of the molecular mechanisms, and promoting translation from bench to bedside of gastrointestinal, hepatobiliary, and pancreatic diseases. The aim of JTG is to provide a forum for the exchange of ideas and concepts on basic, translational, and clinical aspects of gastroenterology, and promote cross-disciplinary research and collaboration.

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