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

tetano

Editor, Senior Moderator
Gut Microbes


. Jan-Dec 2022;14(1):2100200.
doi: 10.1080/19490976.2022.2100200.
Alteration of the gut microbiota's composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters


Valentin Sencio[SUP] 1 2 3 4 5 [/SUP], Nicolas Benech[SUP] 3 5 [/SUP], Cyril Robil[SUP] 1 2 3 4 5 [/SUP], Lucie Deruyter[SUP] 1 2 3 4 5 [/SUP], Séverine Heumel[SUP] 1 2 3 4 5 [/SUP], Arnaud Machelart[SUP] 1 2 3 4 5 [/SUP], Thierry Sulpice[SUP] 6 [/SUP], Antonin Lamazière[SUP] 7 8 [/SUP], Corinne Grangette[SUP] 1 2 3 4 5 [/SUP], François Briand[SUP] 6 [/SUP], Harry Sokol[SUP] 7 8 9 [/SUP], François Trottein[SUP] 1 2 3 4 5 [/SUP]



Affiliations

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.

Keywords: COVID-19; NASH; SARS-CoV-2; gut microbiota; hamsters; obesity.
 
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