Therapeutic manipulation of the microbiota: past, present, and considerations for the future.
BACKGROUND
The growing appreciation of the potential role of indigenous microbiota in disease has resulted in a concomitant interest in manipulating the microbiome for therapeutic effect. The most successful example of microbiota manipulation for treatment of a disease is in recurrent infection with the bacterial pathogen Clostridium difficile.


OBJECTIVE
This review provides historic perspectives on development of microbiota transplantation and reviews evidence for its use in recurrent C. difficile infection.


METHODS
A PubMed search of the terms ([fecal transplant OR fecal transplantation] AND difficile) to 9 June 2016 yielded 415 articles.


BACKGROUND
Recent work has pointed to potential mechanisms by which microbiota restoration in the form of faecal transplantation has been efficacious. This includes studies of microorganisms associated with successful faecal transplantation in human and animal studies and a focus on bacterial bile acid metabolism as a mechanism that mediates colonization resistance against the pathogen. The potential use of microbiota manipulation for other diseases such as inflammatory bowel diseases and metabolic disorders will be discussed. The case will be made that the lessons learned from treatment of recurrent C. difficile infection may not necessarily translate to use of faecal transplantation or other methods to alter the microbiome for the treatment of other diseases.


CONCLUSIONS
A key conclusion that can be drawn is that understanding of the precise role of the microbiota in the pathogenesis of a specific disease is necessary prior to determining if microbiota manipulation represents a novel treatment therapy.
Department of Internal Medicine/Infectious Diseases Division, Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: youngvi@umich.edu.
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D000818:Animals; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000628:therapy*; D004195:Disease Models, Animal; D000069467:Fecal Microbiota Transplantation / Q000266:history / Q000379:methods*; D005243:Feces / Q000382:microbiology; D049673:History, 20th Century; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D064307:Microbiota
Clostridium difficile; Colonization resistance; Faecal microbiota transplant; Microbiome; Microbiota