Gut microbial allies and adversaries in SARS-CoV-2 infection

While the immediate threat of coronavirus disease 2019 (COVID-19) has diminished, the World Health Organization (WHO) still considers it an important public health concern, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate at considerable levels. The gut plays an important role in host responses to viral infections, yet its functional role in SARS-CoV-2 infection remains largely unexplored. We conducted a cross-sectional study, including 63 SARS-CoV-2-positive patients and 54 healthy controls, to identify differences in clinically relevant parameters (biochemical and haematological) and in gut microbiota composition, analysed by full-length ribosomal ribonucleic acid (rRNA) operon amplicon sequencing (16S-ITS-23S) on the MinION platform. To evaluate the ability of commensal bacteria inversely associated with COVID-19 to modulate the immune response and intercept SARS-CoV-2's cell entry and infectivity, we performed functional in vitro assays using a vesicular stomatitis virus (VSV) pseudovirus modified to express the S protein of SARS-CoV-2. COVID-19 patients showed lower serum vitamin D, reduced gut microbiota richness and diversity, increased abundance of Enterococcus faecalis, and decreased abundance of five commensal bacterial species. Of these, Bacteroides uniformis exhibited immunomodulatory effects that could mitigate the exacerbated immune response characteristic of severe COVID-19 cases, without affecting viral entry and infectivity. Thus, our study suggests that specific commensal bacteria might modulate the immune response and, thus, mitigate COVID-19 prognosis. These results illuminate the complex relationship between COVID-19 and the gut microbiota, with potential implications for disease management and enhanced preparedness for future viral threats.