GUT MICROBIOTA IS IMPLICATED IN CANCER-INDUCED CACHEXIA

BACKGROUND AND AIMS : We know that the gut microbiota is implicated in energy metabolism and it role has been mostly studied upon obesity . Here we set the hypothesis that the gut microbiota could also be implicated in metabolic alterations associated with cancer, cachexia. METHODS : This hypothesis was assessed in BALB/c mice intravenously injected with mouse proB BAF3 cells transfected with BCR-ABL gene in order to allow the development of chronic myelogenous leukemia (CML). Muscles (tibialis, gastrocnemius), liver, intestine and adipose tissues were withdrawn 2 weeks after injection for further biochemical and histological analysis. Gut microbiota composition was assessed by RT-qPCR. RESULTS : BCR-ABL expressing CML constitutes a new model of cancer cachexia, as proven by a decrease in adipose and muscle tissue weights. In both male and female, Lactobacillus spp. levels in caecal content drastically decrease, independently of food intake (p<0,001). Moreover, this decrease is highly correlated to muscle markers of atrophy, such as Atrogin-1 mRNA (r = -0,8885, p<0,0001). Finally, increasing the level of Lactobacillus spp. levels by dietary prebiotics allows to lessen Atrogin-1 mRNA induction in the muscle. CONCLUSIONS : In this new model of cancer cachexia, we highlight two important facts : first, gut microbiota modification is associated with cancer-induced cachexia ; second, modulation of gut microbiota counteracts markers of muscle atrophy. Therefore, we suggest that gut microbiota is implicated in cancer cachexia and may constitute a new target in the treatment of this metabolic disease