Dr. Chaysavanh Manichanh, head of the laboratory of Microbiota of the group for Research in Physiology and Digestive Physiopathology of the Vall d'Hebron Research Institute (VHIR) has obtained a grant of 200.000 dolars of the Litwin IBD Pioneers program granted by the Crohn's and Colitis Foundation of America to carry out the project Microbiomarkers for the prediction and diagnosis of relapses in Crohn's disease after surgery.

The project led by Dr. Manichanh consists of the early identification of patients at higher risk to develop an outbreak of the Crohn's Disease (CD) after having a surgery to resect the part of intestine affected. If these relapses are predicted, early preventive treatment of the new outbreak could be started. The objective is to identify these patients before surgery and in those cases where it is not possible try to differentiate between one or two months after the intervention.

Crohn's disease is one of the two main forms of inflammatory bowel disease. Up to 70% of patients with a more serious CD may need surgery to remove parts of their intestine within a time frame of 10 years, but this intervention may result in recurrence without the cause of these relapse being known for the moment or new outbreaks.

The need for a surgical intervention is mainly due to the low or no response to therapy, stenosis, abscesses or fistulising disease. Despite the resection, new lesions may return few months after intervention or even years later so there are patients who require multiple resections for life.

In this sense, the alteration of the intestinal microbiota has been described in CD in previous works and it is believed that it may play an important role in the early events of the recurrence following surgery. Early postoperative CD recurrence (POR) is one of the best human models to study early triggers of inflammation.

"The aim of the project is to determine if it is possible to prognosticate early recurrence based on microbial parameters at the time of surgery," says Dr. Manichanh. Our project will also provide new insights into the composition and role of microbiota in CD and may lead to new diagnostic, predictive or therapeutic strategies," she adds.

To do this, they will unravel the sequence of events taking place before and at the time of the development of the early inflammatory lesions. They will investigate if compositional or functional microbial changes prelude or follow the immune reaction changes of the host tissue by studying the microbiota and cytokine profiles during and after resolution of inflammation in this clinical scenario mimicking the natural onset of the disease.

For this purpose, longitudinal analysis of both fecal/mucosal microbial and cytokine profiles in CD patients undergoing an ileocaecal resection of the diseased bowel will be performed. "By using metagenomic analysis, we aim to deepen the novel findings to provide a more comprehensive picture on the role of the microbiota in the CD. This will allow enterotype description, network analysis of ecosystem shifts and the potential discovery of new biomarkers of Crohn's disease," she reports.

"Finally, they will work to develop a score that can be used in clinical practice to stratify patients according to high and low risk of recurrence. According to this risk score, it could be proposed a new algorithm for the treatment of postoperative recurrence", explains Dr. Chaysavanh Manichanh.

The project, which will last for two years, has the support of the doctors Severine Vermeire and Katlhleen Machiels of the KU Leuven University in Belgium that provide patient specimens on which the research is conducted.


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