The COVID-19 pandemic has highlighted the complex interplay between the gut microbiota and systemic immune responses, particularly through the gut–lung axis. Disruptions in gut microbial diversity and function—commonly referred to as dysbiosis—have been increasingly implicated in the pathogenesis of SARS-CoV-2 infection. In this study, we assessed the gut bacteriome and permeability in SARS-CoV-2-infected patients using 16S sequencing and ELISA assays, respectively. We also measured blood inflammatory cytokines and fecal secretory IgA to evaluate systemic and mucosal immune responses. Significant alterations in both alpha and beta diversity metrics were observed in patients with COVID-19 (n = 79) and those with post-COVID-19 condition (n = 141) compared to the controls (n = 97). Differential abundance and taxonomic analyses revealed distinct microbial profiles in the infected groups. Increased plasma levels of IL-2, IL-6, IL-17A, IFN-γ, and zonulin were detected in patient samples. Some genera were elevated during acute infection, which was positively correlated with C-reactive protein, while Enterobacteriaceae and Escherichia-Shigella were associated with increased zonulin levels, indicating compromised intestinal barrier function. These findings suggest that gut dysbiosis may contribute to bacterial translocation and systemic inflammation. Overall, our results highlight the importance of the gut–lung axis and suggest that modulating the gut microbiota could support immune regulation in SARS-CoV-2 infection.

The COVID-19 pandemic has emerged as one of the most significant global health crises in modern history. The gut microbiota plays a pivotal role in the gut-lung axis, influ-encing both local and systemic immune responses. Disruptions in gut microbiota have been implicated in the COVID-19 pathogenesis. We evaluated the gut bacteriome and permeability in SARS-CoV-2-infected patients by 16S sequencing and ELISA assays, respectively. We also measured serum inflammatory cytokines and fecal sIgA levels. We observed significant differences in Richness, Chao1, Shannon, and Faith's phylogenetic diversity metrics in SARS-CoV-2-infected patients, when compared with controls, as well as, different clusters in beta diversity analyses. Regarding differential abundance analysis and taxonomic distribution, we observed significant differences between SARS-CoV-2-infected group and controls. We detected increased serum IL-2, IL-6, IL-17A, IFN- and zonulin concentrations in patients. Some differentially increased genera in acute COVID-19 correlated with C-reactive protein levels. In the same way, some taxa correlated with increased zonulin concentrations, including Enterobacteriaceae and Esche-richia-Shiguella, suggesting the role of gut dysbiosis in impaired barrier function, aug-menting bacterial translocation and systemic inflammation. Our results reinforce the importance of the gut-lung axis and the role of the gut microbiota in modulating the immune responses and maintaining the intestinal barrier integrity, suggesting the ca-pacity to modulate the immunity to SARS-CoV-2 through the gut microbiota.