Exploration of the contribution of the gut microbiota and its metabolism to cancer cachexia

Cancer cachexia is a complex multi-organ syndrome characterised by body weight loss, weakness, muscle atrophy and fat depletion. The modulation of the gut microbiota, an important regulator of the host metabolism, has shown therapeutic potential. To evaluate the contribution of gut microbiota alterations to the metabolic dysfunctions observed in cancer cachexia, we first investigated the role of Klebsiella oxytoca. We found that this Enterobacteriaceae species acts as a gut pathobiont by altering the gut barrier function in cachectic mice. Then, a multi –omics strategy revealed multiple host metabolic alterations and a reduction of different beneficial intestinal bacterial activities in cachectic mice. Finally, we used a multi –omics approach to show that acute myeloid leukemic patients display gut microbiome alterations at diagnosis. Such alterations may contribute to metabolic and inflammatory dysregulations in those patients. By combining preclinical and clinical data, this thesis work pinpoints important metabolic and microbial alterations in cancer cachexia and shows the interest of this research field for future therapeutic applications.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202