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31/10/2019

A single fecal microbial transplant can modulate the microbiome and improve the clinical manifestations of colitis in an animal model

TMF_colitis_884

31/10/2019

The transplantation of the fecal microbiota restores the intestinal microbiota and, in combination with anti-inflammatory drugs, can be a good candidate for treatment for inflammatory bowel diseases.

Intestinal inflammatory disease (IBD) is a complex illness in which there are imbalances in the microbiota (dysbiosis) and an exaggerated activation of the immune system, causing alterations in the intestinal barrier. The team that leads the Dra. Chaysavanh Manichanh, head of the Microbiota Laboratory of the http://en.vhir.org/portal1/grup-equip.asp?s=recerca&contentid=187018 Research Group in Physiology and Pathophysiology of the Digestive Tract of the Vall d'Hebron Research Institute (VHIR), has published a study in which they demonstrate that the transplant of the fecal microbiota restores the intestinal microbiota and in combination with anti-inflammatory drugs, may be a good candidate for treatment for IBD, specifically, for ulcerative colitis and Crohn's disease. The study, carried out in rats and mice, is published in the magazine https://www.ebiomedicine.com/article/S2352-3964(19)30666-8/fulltext EBioMedicine.The researchers took as a starting point previous studies that indicate the effectiveness of the transplant of fecal microbiota (TMF) to treat infections by Clostridium difficile (C. difficile) in clinical trials in humans. In general, the effects of TMF are little studied, both in clinical trials and in the appropriate animal models in IBM. For this reason, the study conducted by Dr. Manichanh raised the goal of choosing the best animal model, between rat and mouse, for the study of the IBD, as well as observing the effects of TMF on the microbiota and on the symptoms of the disease.The first step was to humanize the microbiota of the rodents by means of a transplant of fecal matter coming from a healthy human donor. In this way the researchers managed to obtain an animal model with a microbiota similar to that of humans. And in this point, "we verified that in the rat model a greater similarity was achieved with the human microbiota and therefore, we followed the study with this animal model," explains Dr. Manichanh. Then, through the administration of dextran of sodium sulphate (DSS), symptoms similar to those of inflammatory bowel disease in humans were induced. DSS is a compound that causes the death of the intestinal epithelial cells and the breakage of the intestinal mucosa, causing the entry of bacteria and stimulating the inflammatory response in the intestine. The researchers observed how DSS causes dysbiosis (loss of bacterial diversity and alteration in the composition of the microbiota), shortening of the colon and alterations in the immune response.Finally, the rats were subjected to another fecal microbial transplant, from the same donor as the initial transplant, to see if it could correct alterations caused by DSS in the microbiota, inflammation and immune response.The researchers used different scales to check the recovery phases. "At the histological level, a physical recovery of the intestinal barrier was checked," Dr. Manichanh. "The DAI score, or severity index of the disease, showed that after TMF the length of the colon recovers, but that recovery is more significant if DSS treatment is also suspended," he adds.The microbiota showed changes, for example, a proliferation of microorganisms similar to those of the microbiota prior to the induction of inflammation and also a recovery of the diversity was demonstrated.The results also showed how treatment in the form of TMF significantly reduces the amount of splenic TCD4 lymphocytes (of the spleen). In those animals that after the second TMF the DSS is removed, that is to say that it is stopped causing intestinal inflammation, an improvement in the injuries to the colon is observed."The results are more effective if the fecal microbiota transplant treatment is done without inflammation (removing the inflammatory agent, the DSS)", concludes Dr. Manichanh. For this reason, in order to use TMF in humans, researchers recommend combining it with an anti-inflammatory treatment or doing so in remission patients, because in this way the results will be better.

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