Microbial Therapeutics in Liver Disease

The intestinal microbiota has long been recognized to play important roles in the pathogenesis and natural history of liver diseases, and antibiotics are routinely used to mitigate some of the common complications of liver cirrhosis. However, progression of liver diseases is associated with decreased microbial diversity in the gut and loss of microbiota-derived signals and metabolites that play important physiologic functions in the host. Therefore, there is growing interest in using live microbial therapeutics that target the intestinal microbiota in patients with liver disease with the objective of restoring these lost activities. Such therapeutics are categorized by regulatory agencies as live biotherapeutic products, which is a new class of drugs that requires development of its own pharmacologic discipline. Currently, the only clinically available representative of this drug class is fecal microbiota transplant (FMT), which can be used in treatment of Clostridioides difficile infections after failure of standard therapies. During the past decade FMT has evolved from crude preparations of homogenized stool to purified, encapsulated microbiota suitable for oral administration. Here we review the liver disease-associated changes in the intestinal microbiota composition and functions and the challenges that need to be tackled in development of live biotherapeutic products for liver diseases.