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, improve 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.