Untangling the link between the human gut microbiota composition and the severity of the symptoms of the COVID-19 infection

Abstract

Recent pandemic infection caused by SARS-CoV-2 (COVID-19) led the scientific community to investigate the possible causes contributing to the physiopathology of this disease. In this context, analyses of the intestinal microbiota highlighted possible correlation between host-associated bacterial communities and development of the COVID-19. Nevertheless, a detailed investigation of the role of the human microbiota in the severity of the symptoms of this disease is still lacking. This study performed a comprehensive meta-analysis of 323 faecal samples from public and novel Italian data sets based on the shotgun metagenomic approach. In detail, the comparative analyses revealed possible differences in the microbial biodiversity related to the individual health status, highlighting a species richness decrease in COVID-19 patients with a severe prognosis. Moreover, healthy subjects resulted characterized by a higher abundance of protective and health-supporting bacterial species, while patients affected by COVID-19 disease displayed a significant increase of opportunistic pathogen bacteria involved in developing putrefactive dysbiosis. Furthermore, prediction of the microbiome functional capabilities suggested that individuals affected by COVID-19 subsist in an unbalanced metabolism characterized by an overrepresentation of enzymes involved in the protein metabolism at the expense of carbohydrates oriented pathways, which can impact on disease severity and in excessive systemic inflammation.

FIGURE 1

Evaluation of microbial biodiversity. Panel (A) displays the Whiskers plot representing the species richness identified from healthy, moderate and severe COVID‐19 subjects. The x‐axis represents the different groups, while the y‐axis indicates the number of species. The boxes are determined by the 25th and 75th percentiles. The whiskers are determined by 1.5 interquartile range (IQR). The line in the boxes represents the median, while the square represents the average. Panel (B) reports the principal coordinate analysis (PCoA) of the faecal samples included in the meta‐analysis, subdivided by health status.

FIGURE 2

Taxonomical and functional comparison between healthy and COVID‐19 subjects. Panel (A) reports the significantly different taxa between groups, reporting prevalence, average abundance, trend, and ANOVA and Tukey HSD post hoc p value. Panel (B) indicates the EC numbers with an increase >400% and a decrease <50% in severe COVID‐19 subjects compared to healthy samples. In detail, the panel reports the average abundance of each group, the trend, the t‐test p value, and the bar plot representing the relative percentage difference. Moreover, EC numbers highlighted in green are related to the metabolism of complex carbohydrates, while EC numbers highlighted in red are related to the protein metabolism.