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

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.