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Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters

Abstract : Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota's composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota's metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.
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Contributor : François TROTTEIN Connect in order to contact the contributor
Submitted on : Tuesday, August 2, 2022 - 8:51:54 AM
Last modification on : Tuesday, November 22, 2022 - 2:26:15 PM
Long-term archiving on: : Thursday, November 3, 2022 - 6:34:19 PM



Valentin Sencio, Nicolas Benech, Cyril Robil, Lucie Deruyter, Séverine Heumel, et al.. Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters. Gut microbes, 2022, 14 (1), ⟨10.1080/19490976.2022.2100200⟩. ⟨inserm-03741928⟩



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