The missing microbes: Bifidobacterium and Faecalibacterium depletion and loss of microbiome diversity as potential susceptibility markers for SARS-CoV-2 infection and severity

Hazan, S.; Stollman, N.; Bozkurt, H. S.; Dave, S.; Papoutsis, A. J.; Daniels, J.; Dolai, S.; Barrows, B. D.; Quigley, E. M.; Borody, T. J.

Objective: To compare gut microbiome diversity and composition in SARS-CoV-2 polymerase chain reaction (PCR)-confirmed positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls. Design: Using a cross-sectional study design, we used shotgun next-generation sequencing (NGS) to evaluate microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections presenting to Ventura Clinical Trials for care from March 2020 through January 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate, or severe symptoms based on NIH criteria.1 Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, e.g. household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls and across patient subgroups at all taxonomic levels. Results: There were 52 patients and 20 controls. Compared with controls, patients had significantly less bacterial diversity, a lower abundance of Bifidobacterium and Faecalibacterium as well as some other bacteria, and a higher abundance of Bacteroides at the genus level. Additionally, there was an inverse association between disease severity and both bacterial diversity and Bifidobacterium and Faecalibacterium abundance. Conclusion: We hypothesize that low bacterial diversity and depletion of Bifidobacterium and Faecalibacterium genera either before or after infection led to reduced pro-immune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for severe symptoms from SARS-CoV-2 infection and may be amenable to pre-, intra-, or post infection intervention.