Gut microbiota dysbiosis and diarrhea in kidney transplant recipientsOriginal paper
What was studied?
This study asked whether early diarrhea after kidney transplantation is linked to gut dysbiosis rather than infection. Researchers profiled the gut microbiota in serial stool samples using 16S ribosomal RNA gene V4-V5 deep sequencing. They also ran a multiplex PCR panel testing 22 bacterial, viral, and protozoan gut pathogens on diarrheal samples. PICRUSt was used to predict metabolic gene functions from the sequencing data. A hierarchical Bayesian logistic regression adjusted for repeated samples and clinical variables.
Who was studied?
The cohort was 71 adult kidney transplant recipients at a New York hospital, followed during the first 3 months after transplant. They provided 199 stool samples in total. Twenty-five recipients developed post-transplant diarrhea. Analysis compared 28 diarrheal samples from 18 subjects against 112 samples from 46 recipients without diarrhea. The study also followed 2 recipients with recurrent Clostridioides difficile who underwent fecal microbial transplantation.
What were the most important findings?
Diarrheal samples had significantly lower diversity than non-diarrheal samples (median Shannon index 2.4 vs 3.1, P below 0.001). Community structure separated clearly by ordination. Thirteen commensal genera were significantly less abundant during diarrhea, many from the Lachnospiraceae and Ruminococcaceae families (butyrate-producing Clostridia). Three genera were higher. Of 28 diarrheal samples, 26 were negative for all 22 tested pathogens; only 2 were positive. Diarrheal samples also showed lower predicted metabolic genes, including sugar-degrading pathways.
What are the greatest implications of this study?
The findings suggest early post-transplant diarrhea usually reflects loss of beneficial commensal bacteria, not common infections. This challenges routine assumptions that immunosuppressant dosing alone explains it. Dysbiosis persisted across mycophenolate mofetil dose groups, arguing the drug dose is not the sole driver. In two fecal transplant cases, diarrhea resolved as depleted taxa recovered. Being observational, the study cannot prove whether dysbiosis causes diarrhea or results from it. Restoring commensal bacteria is a plausible avenue for future treatment research.