Therapies to modulate gut microbiota: Past, present and future

Abstract

The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.

Keywords: Fecal microbiota transplantation; Microbial replacement therapies; Clostridioides difficile infection; Microbiome; Microbiota; Inflammatory bowel disease

Core tip: The human gut microbiota comprises of a diverse array of microorganisms responsible for the maintenance of health. Disruption of this microbial milieu has been implicated in various disorders. These include, but are not limited to, diseases such as Clostridioides difficile infection and inflammatory bowel disease. Microbial replacement therapy or fecal microbiota transplantation is highly effective for treating recurrent Clostridioides difficile infection. Its role in other gastrointestinal and non-gastrointestinal disorders is under investigation. This review summarizes the current indications and evidence for the use of such therapies, and briefly touches upon potential therapeutic applications in the future.