Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection

Abstract

As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in the development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of fecal microbiota transplantation. We discuss opportunities for treatment of other diseases with fecal microbiota transplantation, based on findings from small clinical and preclinical studies.

Keywords: Cancer; Fecal Microbiota Transplantation; Inflammation; Metabolic Syndrome; Microbial Manipulation.

Figure 1:. Potential Application of FMT to Cancer Therapy

Intrinsic and extrinsic factors can disrupt healthy intestinal microbiota and increase susceptibility to cancer. Replacement of the intestinal microbiota with FMT might be used to prevent or treat different forms of cancer including colorectal, liver, and pancreatic cancer.

Figure 2:. Synergy of the Intestinal Microbiota With the Immune System in Cancer

Treatment Specific microbes or their products could increase the activities of chemotherapeutic or immune checkpoint inhibitor therapy, perhaps through interactions with immune cells.

Figure 3:. Searching for Microbe-based Therapeutic Targets

Microbe-based therapies could replace the entire intestinal microbiota, such as in FMT (first generation), involve specific combinations of microbes (second generation), or microbe-derived compounds (third generation). Studies are underway identify the microbes or products that are altered during disease development and therefore might be therapeutically targeted, or microbes or molecules with therapeutic effects. Once identified, these require validation and prospective clinical studies.