Gut microbiota, inflammatory proteins and COVID-19: a Mendelian randomisation study

Area of Science:

• Microbiology
• Immunology
• Genetics

Background:

• The human gut microbiota is implicated in COVID-19 development, potentially via inflammatory pathways.
• Understanding gut microbiota-COVID-19 links is crucial for early diagnosis and targeted therapies.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and COVID-19.
• To determine the mediating role of inflammatory proteins in this association.

Main Methods:

• Bidirectional Mendelian randomization (MR) and two-step mediated MR analyses were employed.
• Investigated associations among 196 gut microbiota, 91 inflammatory proteins, and COVID-19.
• Utilized inverse variance weighted (IVW) and Bayesian weighted Mendelian randomization (BWMR) methods with external validation and meta-analyses.

Main Results:

• Seven gut microbiota were significantly associated with COVID-19 risk.
• Five inflammatory proteins showed associations with COVID-19 risk (three positive, two negative).
• CCL2 was identified as a mediator between specific gut bacteria (Bifidobacteriaceae, Bifidobacteriales) and COVID-19, explaining 12.73% of the causal pathway.

Conclusions:

• Genetic causation exists between specific gut microbiota and COVID-19.
• CCL2 acts as a key inflammatory mediator in the gut microbiota-COVID-19 relationship.
• Findings enhance understanding of COVID-19 pathogenesis.