By Will Boggs MD

NEW YORK (Reuters Health) - Fecal microbiota transplantation can be effective for recurrent Clostridium difficile infection, but new-onset obesity could follow transplant of stool from an overweight donor, say the authors of a case report.

"Fecal transplant has helped a lot of people who have run out of other options," Dr. Colleen R. Kelly, from Warren Alpert School of Medicine of Brown University, Providence, Rhode Island, told Reuters Health by email. "However, there is a lot we don't know in terms of side effects/risks and long-term safety."

Dr. Kelly and Dr. Neha Alang, from Newport Hospital, Rhode Island, report the case of a 32-year-old woman with recurrent C. difficile infection who received a fecal microbiota transplant from her 16-year-old daughter.

She had no further recurrence of her C. difficile infection after the transplant, according to the February 1 Open Forum Infectious Diseases online report.

Prior to her illness, she had always been of normal weight. In the 16 months after her fecal microbiota transplant, the patient reported an unintentional weight gain of 34 pounds. By 36 months post-transplant, she had gained another seven pounds despite efforts to diet and exercise.

"This patient's weight gain was dramatic and disturbing," Dr. Kelly said. "She told me she felt like a 'switch flipped' in her body after the fecal transplant, and she has been unable to get back to a healthy weight despite great efforts."

In the meantime, her daughter's weight increased from about 140 pounds (BMI=26.4) to 170 pounds.

Animal models support the notion that fecal microbiota transplantation can trigger or contribute to obesity. Unfortunately, the researchers note, they did not have microbiome sequencing to compare the patient and the donor.

Dr. Kelly also said that other factors could have contributed to her weight gain: "She was ill for a while; perhaps weight gain related to increased intake, which she kept up after getting better. . . . Perhaps genetics . . . her daughter was heavy before she was. Patient remembers going on oral contraceptives shortly after; another possible factor."

"(We) need much more research and probably a national registry to follow these patients for a period of time after fecal transplant," Dr. Kelly said. "There is a lot of excitement around fecal transplantation right now for other things; we must remember it's experimental and unproven therapy."

In the meantime, the authors recommend selecting non-overweight donors for fecal microbiota transplantation.

Dr. Ana A. Weil and Dr. Elizabeth L. Hohmann, from Massachusetts General Hospital and Harvard Medical School, Boston, wrote an editorial related to this report. They told Reuters Health in a jointly authored email, "Groups using family members or intimate partners as donors have proposed and used less rigorous lab testing and phenotyping of donors for numerous practical reasons."

"We don't yet know the entire spectrum of risks and benefits, for the short and the long term," they added. "For that reason, we should use caution in choosing donors, and more importantly in choosing patients who are deemed in need of fecal microbiota transplant (FMT). Yet, (we) would emphasize that for some patients FMT can be life-changing and even life-saving, such as patients with recurrent severe C. difficile infection."

"At this point the data on FMT is overwhelmingly positive," Dr. Natasha Bagdasarian, from Wayne State University, Detroit, Michigan, who recently reviewed the diagnosis and treatment of C. difficile infection (CDI) in adults, told Reuters Health by email. "This procedure has been used successfully for severe and refractory cases of CDI, with few reports of adverse outcomes."

"I do not think that this case report describing weight gain after FMT should make clinicians hesitate in using the procedure to treat those patients who are experiencing the consequences of refractory CDI, which include dehydration, weight loss, repeat admissions to the hospital, electrolyte imbalances, kidney injury, sepsis and even death," she said.

"The authors seem to imply that the daughter in the case was a 'non-ideal' donor because she was overweight," Dr. Bagdasarian said. "However, I would like to point out that her BMI was 26.4 at the time of FMT, which is only slightly higher than the ideal range, and was in fact similar to the BMI of the recipient at the time of FMT. Given the logistics of finding and screening a donor prior to FMT, it may not always be practical to find a donor with an ideal BMI."

Dr. Josbert Keller, from Medisch Centrum Haaglanden, The Hague, The Netherlands, has studied and reported on both CDI and FMT. He told Reuters Health by email, "This is a case report, that does not prove any direct association between weight gain and FMT. However, all physicians treating patients with FMT should be aware that unexpected side effects can occur."

"The exact role of the microbiota in health and disease is largely unknown," Dr. Keller said. "FMT is a novel and unstandardized treatment approach and may be less safe than expected; very few reports about the long-term consequences have been published."

Dr. Keller concluded, "I believe that donors should be entirely healthy. Obesity is in my opinion a reasonable exclusion criteria, because the microbiota of obese patients differs from the microbiota of healthy/lean persons."

Dr. Arnab Ray, head of the Gastroenterology Section at Ochsner Clinic Foundation, New Orleans, Louisiana, told Reuters Health by email, "I've treated about 60 patients with fecal transplant and I had a case similar to this a few weeks ago. My patient was extremely grateful for eradicating her C diff, but she had unintentionally gained 10 pounds since the procedure despite dieting and exercise. In her case, she had no one to donate stool to her (her only friend was a service dog), so we had to use an anonymous tandem donor who had recently donated to a family member."

"This case sheds light on the problems of finding an ideal donor for a fecal transplant, namely that we don't know how to define one, and it is difficult to find an ideal donor when 1 out of 3 adults in this country are obese," Dr. Ray said. "I work with OpenBiome, the country's first frozen stool bank to provide fecal material for my patients from healthy donors. We need to support and standardize endeavors such as this."

"In my practice, I would say at least 80% of my recurrent C. diff. patients are women," he added. "There is something about their microbiota which seems to make them more susceptible to this disease. We need to find out why."

Dr. Ray works with Rebiotix, a company that is working to develop a standardized fecal transplant product. The study authors make no disclosures.


Open Forum Infect Dis 2015.