Autoimmune liver diseases pose a serious challenge to modern medicine, as many patients fail to respond to existing therapies, which are often accompanied by severe side effects. Current data support the use of bacteriophages to restore immune homeostasis and reduce inflammation in certain liver diseases*.

Autoimmune liver diseases include such major entities as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. The etiology of these diseases is complex and poorly understood, and autoimmune processes are only one link in their pathogenesis. Immunosuppressive therapy is effective in only some patients, but in others, it does not produce a satisfactory response. Treatment of patients with primary biliary cirrhosis and primary sclerosing cholangitis is particularly challenging.

Recently, data has accumulated on the beneficial effects of bacteriophages in autoimmune processes in the liver. Studies have shown that when administered orally, bacteriophages accumulate in Kupffer cells—specialized liver macrophages—and, by modulating their activity, reduce autoimmune damage to the organ. This approach is safe and virtually free of side effects, making it particularly attractive compared to traditional immunosuppressive therapy. Bacteriophages also reduce reactive oxygen species in the liver, inhibit the activation of TLR-4 and NF-κB, and inhibit proinflammatory and procoagulant platelet activity. They simultaneously stimulate the production of protective anti-inflammatory factors: interleukin-10 and interleukin-1 receptor antagonist.

There is evidence that, in addition to autoimmune factors, infectious factors play a role in the pathogenesis of primary sclerosing cholangitis: destruction of the intestinal mucosa by intestinal bacterial toxins facilitates the translocation of bacteria into the bloodstream, their entry into the liver, and the development of inflammation. Thus, bacteriophages can serve as both immunomodulatory and antimicrobial agents.

Recently, a biotech company announced** that it is preparing to test a phage preparation for the treatment of primary sclerosing cholangitis. Company representatives note that while studying the mechanisms of intestinal barrier dysfunction in this disease, a specific strain of the bacterium Klebsiella pneumoniae capable of destroying intestinal epithelium was discovered in the intestinal microbiome of patients. Researchers believe that this strain plays a key role in the pathogenesis of primary sclerosing cholangitis. Now that the target bacterium is known, it's time to create an effective phage cocktail to destroy it.

* Górski A, Jończyk‐Matysiak E, Łusiak‐Szelachowska M et al. Therapeutic potential of phages in autoimmune liver diseases // Clin Exp Immunol, 2018, 192(1): 1–6. doi: 10.1111/cei.13092

** BiomX licenses novel targets for phage therapy program