Manipulating the Human Microbiome to Manage Disease

More than a decade after the launch of the Human Microbiome Project, research in this field has grown exponentially, with studies associating microbial states or species with disorders including novel infectious etiologies and complex human disease. Scientists are searching for the potential utility of the microbiome (the community of bacteria, fungi, and viruses in an environment), with particular focus on manipulating microbial communities as novel therapeutic modalities. This Viewpoint highlights current applications of microbiome science to human health and examines successes and remaining challenges.

Fecal microbiome transplantation (FMT) has demonstrated the potential for normal human-associated microbes to ameliorate or even cure disease. In 2013, van Nood et al1 reported the results of a single-center trial that used duodenal infusion of donor feces to manage recurrent Clostridioides difficile infection (CDI; formerly known as Clostridium difficile). Forty-three patients were randomized to receive FMT, oral vancomycin, or vancomycin plus bowel lavage. The trial was terminated early when FMT was deemed more effective than antibiotic therapy, with 13 recipients (81%) cured by a single infusion. In total, 15 participants (94%) who received FMT had resolution of CDI compared with 4 (31%) who received antibiotics alone and 3 (23%) who received antibiotics plus lavage. Additional studies have shown that FMT can be used to treat CDI. However, questions about the how and why of the clinical effectiveness of FMT remain unanswered. For instance, do donor strains stably colonize the gut? Are complex communities of fecal microbes required for success? Mechanistic studies are required to understand the differential responses in FMT recipients as well as safe therapeutic and experimental implementation, given the potential for FMT-related transmission of serious viral infections or multidrug-resistant bacteria.

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