PT - JOURNAL ARTICLE AU - Sabine Hazan AU - Neil Stollman AU - Huseyin S Bozkurt AU - Sonya Dave AU - Andreas J Papoutsis AU - Jordan Daniels AU - Brad D Barrows AU - Eamonn MM Quigley AU - Thomas J Borody TI - Lost microbes of COVID-19: <em>Bifidobacterium</em>, <em>Faecalibacterium</em> depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity AID - 10.1136/bmjgast-2022-000871 DP - 2022 Apr 01 TA - BMJ Open Gastroenterology PG - e000871 VI - 9 IP - 1 4099 - http://bmjopengastro.bmj.com//content/9/1/e000871.short 4100 - http://bmjopengastro.bmj.com//content/9/1/e000871.full SO - BMJ Open Gastro2022 Apr 01; 9 AB - Objective The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.Design Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.Results Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p&lt;0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.Conclusion We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.Trial registration number NCT04031469 (PCR−) and 04359836 (PCR+).Data are available upon reasonable request. Data available upon reasonable request from corresponding author, Dr. Sabine Hazan.