The Human Microbiome and Fecal Microbial Transplantation

“The role of the infinitely small in nature is infinitely great” Louis Pasteur.

The microbiome refers to the aggregate of all microbial species while microbiota refers to individual bacterial species. Of recent there has been a lot of interest in the human microbiome and especially the gut microbiome and its’ role in disease. There are over 100 trillion organisms in the human body, comprising 90% of cells. There are 100 fold more genes in our gut than in the rest of us. Our flora, the ecosystem within us, is as unique as a fingerprint and a very important part of us. Firmicutes and Bacteroides comprise 90% of gut microbiota and diversity of gut flora appears to be a crucial factor in health. They play a role in inflammation, immunity, infection and metabolism.

The GI microbiome (GIMB) composed of 2000-5000 species functions almost like an independent organ, having, anatomy, physiology, ontogeny and can be disturbed in pathological conditions. It is acquired during the perinatal period and remains fairly constant in the absence of major dietary changes and use of frequent antibiotics.

Like other organs, it can therefore also be transplanted, and the recipient microbiome becomes similar to that of the donor¹.

Alteration in the GIMB is believed to play a role in a variety of illnesses including, recurrent C Difficile infection, obesity, psychological disorders, metabolic syndrome, autoimmune arthritis and inflammatory bowel disease. FMT involves the transfer of stool from a healthy donor to one with an illness. The procedure involves identifying a healthy donor, analogous to blood transfusion donors. The donor stool is prepared by mixing with saline, filtered and is delivered via colonoscopy or nasoduodenal tube. The colonoscopic route, albeit more expensive, is associated with less side effects. Home administered enemas are also used. Frozen stool tablets via stool banks are now available but not FDA approved.

Studies have shown an 80% response rate in recurrent C Difficile which is currently the only indication off clinical trial, for this procedure². C Difficile is acquired via the fecal oral route, with illness brought on by use of antibiotics or immunosuppression. Recurrent C Diff is associated with a different GIMB to healthy persons. It appears that the loss of diversity is as important as proliferation of certain species. With the restoration of the GIMB with FMT from a healthy gut, the infection resolves.

The data for use of FMT in ulcerative colitis is conflicting even though there is a demonstrated difference in the GIMB of patients with IBD compared to healthy controls^3 4. Some studies have shown improvement and others not, but there is a paucity of controlled trials. Conflicting study results are probably due to different modes of delivery, number of transplant episodes and donor differences. There are several trials underway which may shed light on the above.

Several institutions offer FMT, single donor, via colonoscopy, including Stony Brook University Hospital (SBUH). It is offered off trial in SBUH for recurrent C Diff and also on a trial protocol for C Diff and ulcerative colitis as well as medication refractory ulcerative colitis alone.

FMT and the study of the human GIMB is a burgeoning field. There are currently numerous studies underway using FMT for a variety of other diseases including obesity, NAFLD/NASH, IBS, DM II, Pancreatitis, MRSA enterocolitis, Drug resistant organisms, hepatic encephalopathy⁵.

¹ Khoruts A. J Clin Gastroenterol, 2010
² Drekonja et al. Ann Intern Med. 201; 162:630-638
³ Moayyedi et al, Gastro 2015
⁴ Rossen et al, Gastro 2015
⁵ Clinicaltrials.gov.2016

– Ramona Rajapakse, MD