Exploring the Role of Gut Microbiota in Regulating Immune Responses to Respiratory Infections: A Cross-Disciplinary Study

Abstract

Common respiratory infections from the common cold to pneumonia are reported to alter the gut microbial community and immune function. This work aims at comparing the gut microbiota and immune markers in healthy people, and patients with mild and severe respiratory infection. For the gut microbiota, alpha diversity was determined by the Shannon index while beta diversity was determined by weighted UniFrac distance using PCoA. We quantified major bacterial phyla and their proportions. T cell activation was assessed by determining the frequency of CD4+ and CD8+ T cells while the levels of IL-6 and TNF-α were used to determine the levels of pro-inflammatory cytokines. Other alterations in metabolism were also investigated, including those in short-chain fatty acids (SCFAs) such as butyrate. These results showed a decrease in alpha diversity in severely infected patients compared with healthy controls and patients with mild infections (p < 0.001). The beta diversity revealed a more significant microbial community shift in severe infections. Some of the changes in the taxa were a reduction in the abundance of beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium while there was an increase in the pathogenic bacteria including Enterococcus faecalis and Escherichia coli. Cytokine analysis showed that the level of activated T cells and cytokines IL-6 and TNF-α was significantly higher in the severe infection group. The metabolomic studies revealed that the levels of butyrate were significantly decreased in severe infection. This study also shows how respiratory infections can affect gut microbiota and the immune system. Systemic infections are characterized by low microbial density, high pathogenic density, and high levels of inflammation. These results imply that the regulation of microbial flora and the immune system may be critical for the prevention of severe respiratory infection.