Wastewater-based Surveillance Reveals Incomplete Gut Microbiome Recovery Following Easing of COVID-19 Restrictions in Wuhan, China

Abstract While SARS-CoV-2 infection is known to disrupt the gut microbiome, its population-level impact and long-term recovery trajectory remain poorly understood. Here, we applied longitudinal wastewater metagenomics in Wuhan, China, to track the compositional and functional dynamics of the gut microbiome in a large urban population over a 15-month period. Within three months following the easing of the “zero-COVID” policy, a marked decline in microbial diversity and depletion of beneficial commensals were observed. Meanwhile, the abundance of fermentative taxa (e.g., Bifidobacterium) increased significantly, suggesting an early-stage compensatory response. Functional pathway analysis revealed elevated fermentation and suppressed biosynthesis (e.g., amino acids), indicating incomplete functional compensation. In parallel, both clinically confirmed pathogens and gut-resident pathobionts (e.g., Clostridioide, Enterococcus, Eggerthella) expanded, along with sustained increases in antibiotic resistance and virulence genes. By month 15, both community composition and functional profiles of commensal taxa largely converged toward pre-policy change baselines. Although taxonomic profiles largely recovered, the elevation of virulence-associated features persisted, suggesting lasting impacts on microbiome-associated health risks. Notably, the diversity of clinically relevant antibiotic resistance genes within commensal taxa increased markedly at the final time point, suggesting a late-stage enrichment of latent resistance reservoirs. Together, these findings reveal an incomplete microbiome recovery, with structural restoration uncoupled from sustained functional disruption. This study provides the first wastewater-based evidence of large-scale gut microbiome restructuring in response to large-scale SARS-CoV-2 infection, highlighting the utility of wastewater metagenomics in revealing hidden public health effects.