Probiotics Reduce Immunosuppression-Related Diarrhea in Kidney Transplant Patients

Jim Kling

May 05, 2010

May 5, 2010 (San Diego, California) — Patients taking the immunosuppressant mycophenolate mofetil (MMF; CellCept, Roche) after a kidney transplant experienced a large improvement in diarrhea symptoms when treated with a multistrain probiotic formula, according to a study presented here at the American Transplant Congress 2010, the joint annual meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.

Immunosuppression frequently leads to gastrointestinal (GI) complications, including immunosuppression-associated diarrhea (IAD). MMF is associated with an adverse event rate of diarrhea and other GI issues of nearly 50%. After organ transplantation, physicians are sometimes forced to alter the immunosuppression regimen to accommodate these problems, but that can lead to increased risk for rejection, noted presenter William Marks, MD, PhD, chief of the Organ Transplant Program at the Swedish Medical Center in Seattle, Washington, at the time the study was conducted, and currently executive medical director at Alexion Pharmaceuticals in Cheshire, Connecticut.

Immunosuppressants can lead to diarrhea by altering microbiota populations in the gut, leading to a reduction of short-chain fatty acids. Dr. Marks and colleagues investigated whether the ingestion of probiotics could restore microbiota balance and bolster short-chain fatty acid production.

Patients undergoing kidney transplantation were recruited for a single-site study and assigned to receive a probiotic blend of Bifidobacterium lactis, B bifidum, B longum, Lactobacillus acidophilus, L rhamnosus, and L paracasei (21 patients), or placebo (22 patients). Probiotic capsules contained about 50 billion colony-forming units. Patients were directed to take 2 capsules twice a day, starting before surgery and continuing for 4 months. Patients were followed for 5 months, with analysis of stool samples and daily questionnaires to document bowel habits. The researchers defined IAD as 2 or more successive days with at least 2 loose stools per day that were unrelated to other illnesses or medications.

Nineteen of 21 patients in the probiotic group completed the study, as did 16 of 22 patients that were randomized to receive placebo. Ten of 16 (62.5%) patients receiving placebo experienced IAD, compared with 3 of 19 (15.8%) patients receiving probiotics (P = .006). Subjects receiving probiotics also had reduced severity of diarrhea symptoms, and experienced no adverse effects.

"This was quite dramatic — a 71.6% reduction in risk of diarrhea," Dr. Marks said during his report. He believes that the multistrain probiotic formula might be superior to single-strain formulas.

Probiotics "are something we've been using for years. In India, we make yogurt at home. [With it], you can repopulate the GI tract," Muralikrishna Golconda, MD, MRCP, professor of internal medicine at the University of California-Davis Medical Center, told Medscape Transplantation.

The research "is interesting. If the drug dose is reduced (because of diarrhea), the patient is at increased risk for rejection. If you can reduce diarrhea, you can use the full dose of the drug," Dr. Golconda added.

The study did not receive commercial support. One of the authors of the study is employed by Prothera, which manufactures the supplement and provided capsules for the study. Dr. Golconda has disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2010: Abstract 96. Presented May 2, 2010.

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