• Sunday, 24 January 2021 - 11:10:57

Thesis: Astrid Kemgang – Liver-intestine interactions in primary sclerosing cholangitis

Febuary 13 - 2019

directed by Chantal Housset & Harry Sokol

(Team Housset)

Primary sclerosing cholangitis (PSC) is a rare disease, of unknown cause, characterized by fibro-inflammatory lesions of the bile ducts. PSC is frequently associated with chronic inflammatory bowel disease (IBD). It is accepted that IBDs result from a disruption of the balance between the intestinal microbiota and the immune system. It is possible that the same mechanisms may be used in the PSC. The most commonly used animal model to study PSC, the Mdr2-/- mouse does not spontaneously develop colitis, however experimental colitis can be induced by sodium dextran sulfate (DSS). First, we conducted a clinical study to analyze the intestinal microbiota of patients with SPC. Our results show that patients with PSC have bacterial and fungal dysbiosis, with a disruption of the correlation network between bacteria and fungi. Second, we conducted a preclinical study to develop an animal model of CSP-MICI (Mdr2 mouse -/- with DSS-induced colitis) to assess the impact of colic disease on liver damage, and vice versa. Our results show that induced colitis in Mdr2-/- mice is more severe than in wild mice. However, colitis improves fibro-inflammatory liver damage in Mdr2-/- mice.
This work shows for the first time the importance of the intestinal fungal microbiota in PSC-associated dysbiosis, as well as the complexity of interactions between the liver and intestine during this pathology.


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