Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity

Abstract

The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies.

Keywords: Dysbiosis; Fecal; Gut; Microbiome; Therapeutic; Transplant.

Fig. 1

Alternative stable states (ball and cup model) of human gut microbial ecosystems. Here we conceptualize the ecological stability of the human gut microbiota as inferred through its species richness. The gut microbial ecosystem is represented as a ball that exists within an equilibrium represented as a cup. The depth of each cup is symbolic of the resilience of a given ecosystem and is related to species richness, where lower diversity leads to lower resilience and the greater the likelihood that the “ball” will roll out of the “cup” into a new state of equilibrium that may be less stable that the first. Perturbational stresses caused by numerous factors such as poor diet, disease state, drug use (including antimicrobials), immunosenescence as examples can impact bacterial diversity and force the ecosystem into a less-stable equilibrium state. Repeated stresses can cause a situation where function may be reduced to the point that dysbiosis and the development of disease ensue.