Phage therapy: Targeting intestinal bacterial microbiota for the treatment of liver diseases Original paper

What was studied?

This paper reviews the role of phage therapy in targeting the intestinal bacterial microbiota for the treatment of liver diseases. It highlights the growing interest in using phages as a therapeutic strategy to manipulate the microbiota and address liver conditions associated with microbial imbalances, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and cirrhosis. The review also discusses phage therapy’s ability to precisely target harmful bacterial populations without causing extensive disruption to the overall gut microbiome.

Who was studied?

The studies referenced in the review predominantly focus on animal models, particularly mice, and clinical case studies involving human patients with liver diseases. The populations studied range from those with liver conditions such as NAFLD, alcoholic liver disease, primary sclerosing cholangitis, and cirrhosis, to patients undergoing phage therapy for various bacterial infections. The paper also references clinical trials that assess the effectiveness and safety of phage treatments, as well as preclinical studies exploring phages’ potential in microbiome manipulation.

Most important findings

The review presents several key findings regarding the potential of phage therapy in liver diseases. It identifies specific bacterial genera in the gut microbiota, such as Bacteroides, Blautia, Dorea, and Prevotella, that are more abundant in patients with liver conditions, suggesting they could be potential targets for phage therapy. The paper also discusses how phages can selectively reduce the abundance of these pathobionts, helping to restore a balanced microbiota. Moreover, phages’ role in reducing inflammation and alleviating liver disease symptoms is emphasized, with studies showing that phages targeting Enterococcus faecalis or Klebsiella pneumoniae can improve liver function in animal models of alcohol-induced liver injury and cirrhosis.

Another important finding is that the use of engineered or synthetic phages, which are designed to broaden the host range and reduce resistance, offers a promising way to overcome challenges associated with natural phages. The paper also mentions that synthetic biology platforms can create phages tailored to target specific bacterial strains, enhancing the precision of phage therapy.

Key implications

Phage therapy’s potential for liver disease treatment highlights its ability to target specific gut bacteria linked to the progression of liver conditions. This targeted approach could offer a more effective and less disruptive alternative to broad-spectrum antibiotics, which can exacerbate dysbiosis. Phage therapy also holds promise for combating antimicrobial-resistant infections, a growing concern in clinical settings. However, the review emphasizes that clinical trials are still necessary to validate the safety and efficacy of phage therapy for liver diseases. Further research should focus on identifying the most suitable bacterial targets, optimizing phage cocktails, and ensuring that phage treatment does not induce significant resistance or cause off-target effects.