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bioRxiv · 10.64898/2026.09.16.751817

Progressive Post-Acute Gut Microbiome Disruption Following SARS-CoV-2 Infection in Mice

Mann-Nuttel, R.·Ogando, N. S.·Armbruster, M.·Mandal, S.·Ospondpant, D.·Elaish, M.·Hobman, T. C.·Power, C.·Forsythe, P.
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Abstract

SARS-CoV-2 infection is increasingly recognized to produce long-lasting physiological disturbances that extend beyond the acute phase. The gut microbiome has emerged as a potential contributor to post-infection outcomes, yet the longitudinal progression of microbial disruption following infection remains poorly defined. Here, we used a mouse model of SARS-CoV-2 infection to characterize gut microbiome dynamics at 7 (late acute phase), 14 (early recovery), and 21 (post-COVID condition, PCC) days post-infection (dpi). Viral RNA was detected in the lungs through 21 dpi. Longitudinal microbiome profiling revealed a two-phase restructuring marked by early shifts in Bacillota and Bacteroidota abundance, followed by pronounced post-acute dysbiosis characterized by reduced diversity, expansion of Bacillota, and near-complete loss of Bacteroidota. Functional pathway predictions showed progressive metabolic remodeling, including disruptions in nucleotide turnover, fermentation, and vitamin-related pathways. Together, these findings demonstrate that SARS-CoV-2 infection drives progressive and sustained alterations in gut microbial composition and function after the transition from acute infection through recovery into PCC.

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Mann-Nuttel, R., Ogando, N. S., Armbruster, M., Mandal, S., Ospondpant, D., Elaish, M., Hobman, T. C., Power, C., Forsythe, P.. 2026-09-18. Progressive Post-Acute Gut Microbiome Disruption Following SARS-CoV-2 Infection in Mice. https://doi.org/10.64898/2026.09.16.751817

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