Alteration of the Intestinal Microbiome

Fecal Microbiota Transplant and Probiotics for Clostridium difficile and Beyond

Stephen M Vindigni; Elizabeth K Broussard; Christina M Surawicz

Expert Rev Gastroenterol Hepatol. 2013;7(7):615-628.

Expert Commentary

Recurrent CDI is an excellent example of alteration of the microbiome, which leads to disease. The use of probiotics has had limited success in treatment of this illness. By contrast, FMT has been shown to be very effective and confirmed in one randomized controlled trial. The use of FMT requires regulation, and the FDA has recently announced that any practitioner must submit an Investigational New Drug application to perform it. FMT, which involves putting filtrate from a whole stool specimen from a healthy individual into the patient, is an effective but relatively crude way to treat this infection. Ultimately, we believe that researchers will identify the key important bacteria necessary to restore colonization resistance and they will become available for therapy. The role of the microbiome in the pathophysiology of and treatment of other diseases requires much further research and well-designed controlled trials before any manipulation of the fecal microbiome can be considered in these diseases.

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Box 1. Various diseases currently being evaluated through intestinal microbiome research ^†.
Fecal microbiota transplant Gastrointestinal disease Recurrent Clostridium difficile infection Inflammatory bowel disease Irritable bowel syndrome and chronic constipation Neurological disease Multiple sclerosis Parkinson's disease Hematologic disease Immune thrombocytopenic purpura Probiotics Gastrointestinal disease Prevention and treatment of C. difficile infection Prevention of antibiotic-associated diarrhea Inflammatory bowel disease, specifically ulcerative colitis and pouchitis Irritable bowel syndrome Traveler's diarrhea Helicobacter pylori infection Acute pancreatitis^‡ Hepatic encephalopathy Cardiovascular disease Atherosclerosis Hyperlipidemia Obesity and metabolic syndrome Diabetes mellitus Allergic disease Allergic rhinitis Dermatitis/eczema Oral disease Dental caries Gingivitis Periodontitis Halitosis Oral candidiasis Gynecological disease Bacterial vaginosis Vulvovaginal candidiasis Infectious disease Respiratory tract infections Ventilator-associated pneumonia HIV/AIDS Infectious mastitis Rheumatologic disease Spondyloarthritis Psychiatric disease Anxiety Depression
^†The effects of microbiome alteration have been studied in the context of the above diseases with varying results. This listing does not condone the use of FMT or probiotics in the prevention or treatment of any individual disease. ^‡Probiotics are advised against in the setting of acute pancreatitis.

Box 2. Future research questions.
Clostridium difficile infection Analysis of gender differences in CDI and recurrent CDI Evaluation of ethnic differences and geographic populations (USA versus Europe versus Asia) Analysis of aging effects on the microbiome Surveillance for increasing community-acquired strains of C. difficile Fecal microbiota transplant Donor stool acquisition and preparation Clinical efficacy of fresh versus frozen stool Development of synthetic stool Responsibility of identifying a donor: transplant recipient versus healthcare provider (i.e., establishing stool banks) Effectiveness Additional randomized controlled trials assessing colonoscopic FMT Clinical trials examining benefit of adjuvant therapies in combination with FMT (e.g., probiotics, monoclonal antibodies, antibiotics and vaccination) Clinical trials of FMT as first-line therapy for severe CDI cases Clinical trials evaluating FMT benefits in other diseases, including IBD and constipation-predominant IBS Analysis of host immune responses, including after treatment with FMT (i.e., alterations and sustainability of serum immunoglobulin levels) Health policy Responsibility for donor screening costs – donor vesus recipient Safety Long-term follow-up of patients post-FMT for monitoring of outcomes and safety Characterization of FMT risks in immunocompromised recipients Probiotics Additional analysis of most effective strains and adequate doses for the management of various diseases Characterization of the risks in immunocompromised hosts Consideration of FDA regulation given potential risks and benefits