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29/01/2020

Microbial burden is a biomarker of fecal microbiota transplant response in patients with Crohn's disease

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29/01/2020

The study shows that a low microbial load on the receptor tissues contributes to the success of fecal microbiota transplantation.

Crohn's disease (MC), one of the two main forms of inflammatory bowel disease (IBD), is a chronic condition so far incurable and of unknown etiology, the prevalence of which is expected to increase exponentially in the next decade. The team led by Dr. Chaysavanh Manichanh, head of the Microbiota Lab in the Physiology and Pathophysiology of the Digestive Tract Research Group at the Vall d'Hebron Research Institute (VHIR), has published a study in which they show that the lower the microbial load on the intestinal mucosa, the greater the likelihood of successful fecal microbiota transplantation as a treatment for Crohn's disease. The work, in which Dr. Eloy Espin and Dr. Marc Martí from the Surgery Unit of the Colon and Rectum of the Vall d'Hebron Hospital, and Dr. Dra. Stefania Landolfi, of the Pathological Anatomy Service, have also participated, has been published in https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30826-6/fulltext" EBioMedicine.Dysbiosis or imbalances in the gut microbiota, along with host genetic predisposition, environmental factors such as diet and antibiotic use, and dysregulated immune responses contribute to the origin and evolution of MC.The environmental and genetic factors cause a deterioration of the intestinal barrier in patients with this disease, which eventually leads to inflammation. That is why current therapies for MC are mainly aimed at reducing inflammation and inducing patient remission. However, they do not address the modulation of the dysbiotic gut microbiota toward a healthier composition that decreases inflammation. Remission of Crohn's disease can be achieved by fecal microbiota transplant (TMF). However, this procedure has a low success rate (30%), which could be attributed to a lack of communication between the recipient's intestinal mucosa and the donor's microbiota. This observation could be partly explained by the multifactorial nature of IBD, a genetic predisposition to pro-inflammatory immune responses, and the dysfunction of the intestinal barrier that prevents transplanted microorganisms from colonizing the recipient intestinal mucosa.To overcome these limitations, VHIR researchers used an in vivo human tissue and an animal model to examine and validate changes in the recipient's intestinal mucosa upon contact with a fecal suspension (FS) obtained from a healthy donor. The mucosal microbiome composition and tissue response were evaluated.The study shows that "low microbial load on recipient tissues is a factor that favours the anti-inflammatory response associated with microbial colonization and, thus, contributes to the success of TMF in patients with Crohn's disease," says Dr Chaysavanh Manichanh. That is, "colonization of the donor's fecal microbiota was more successful in tissues with low microbial load than in those with high microbial load," she emphasizes.In addition, donor samples should contain as low as possible a relative abundance of three bacteria: Bacteroides, Parabacteroides, and Enterococcus faecalis, which have been shown to be associated with the release of proinflammatory cytokines. In conclusion, the results indicate that "the strategy to ensure successful colonization would be to select patients who are in remission or who will undergo clinical remission and those who have a low microbial load on the tissue", concludes Dr Manichanh.

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