Role of the intestinal microbiota in diarrhea after kidney transplant

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Intestinal dysbiosis is thought to be at the root of diarrhea in kidney transplant recipients. This is an important finding to consider to improve diagnosis and management.

 

In the year following their kidney transplant, patients may suffer from diarrhea which impairs their quality of life and can lead to rejection of the graft–or even to death. A team in New York attempted to determine the extent to which the intestinal microbiota of patients could be involved in the occurrence of this diarrhea. The researchers collected stool samples from 71 kidney transplant recipients on the first, second, fourth and twelfth weeks after transplant. Twenty-five of these patients suffered from diarrhea, of whom eighteen were able to provide samples.

Deleterious changes in 16 bacterial genera

It emerged that the patients suffering from diarrhea had an intestinal microbiota that was less diversified and less abundant in 13 commensal bacterial genera (in particular Ruminococcus, Dorea, Coprococcus and Bacteroides) already identified by this same team in a previous study. Conversely, the proportions of Enterococcus, Escherichia and Lachnoclostridium were higher, even in the samples collected outside of the antibiotic prophylaxis period–as immunosuppressive treatment can promote infection. Moreover, apart from two samples positive for Yersinia enterocolitica, no patient was infected by a pathogen known to trigger diarrhea–whether of viral, parasitic or bacterial origin. Assay of mycophenolate mofetil (MMF), one of the standard anti-rejection treatments, was also performed: some practitioners in fact choose to reduce the MMF dose to alleviate the diarrhea, potentially increasing the risk of rejection. Here, reduction of the MMF dose (1g versus 2g per day) did not have a major impact on the occurrence of diarrhea.

Less fermented carbohydrates

Is the diarrhea then caused by the intestinal dysbiosis, or does it cause the dysbiosis? In two patients the diarrhea stopped in the month following a fecal microbiota transplant which restored the proportions of the 16 altered bacterial genera, suggesting that an intestinal dysbiosis might be at the root of a metabolic disorder responsible for diarrhea. The researchers consider that the mechanism at work is likely to be the following: most of the bacteria whose level was reduced degrade complex carbohydrates–glucose, fructose, pectin, and others–and produce butyric acid, a short chain fatty acid (SCFA) necessary to the proper functioning of colonic cells. If these results were confirmed in other studies, particularly in studies including the diet of kidney transplant recipients, correction of intestinal dysbioses would improve the management of such patients.

 

Sources:

JR Lee et al. Gut microbiota dysbiosis and diarrhea in kidney transplant recipients. Am J Transplant, 2018 Jun 19