The lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity

Abstract

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.

Gut microbiota and COVID-19: A systematic review

“…One study has reported a decline in Faecalibacteriumprausnitzii in COVID-19 patient gut micro ora samples [78], while the other included study reported an increase in this genus [42]. Similarly, a signi cantly lower abundance of Faecalibacterium among COVID-19 patients was reported by Hazan et al, who also reported that the increase of Faecalibacterium genus and F. prausnitzii species was inversely associated with SARS-CoV-2 positivity and COVID-19 severity [132]. In addition, many studies have linked Faecalibacterium decrease to COVID-19 severity [38,117].…”

“…In general, Bi dobacterum reduces cell injury by inhibiting TNF-α and macrophages by enhancing Treg response [131]. Similar studies also reported a decline in Bi dobacterium of COVID-19 patients' gut microbiome and concluded that this decline would cause a reduced immune function, thus will result in a symptomatic SARS-Cov-2 infection [132]. All this information emphasizes the vital effects of this genus in regulating the immune system and outlines that its decline among COVID-19 patients would have detrimental impacts on the prognosis and severity of the disease.…”

Viral infectious diseases severity: co-presence of transcriptionally active microbes (TAMs) can play an integral role for disease severity

“…SARS-CoV-2 infection has been reported to induce nasopharyngeal fungal microbiome dysbiosis with significant differences in microbiome diversity between COVID-19 patients and healthy individuals wherein Saccharomyces cerevisiae, Candida albicans, Candida glabrata, Aspergillus flavus, Aspergillus fumigatus, Phaffia rhodozyma and Paecilomyces variotii are the predominant fungal pathogens found in the infected patients (113,114). Moreover, studies have found a significant association between the gut/intestinal microbiome alterations and disease severity in the COVID-19 patients, with commensal microorganisms being underrepresented (115,116).…”

“…SARS-CoV-2 infection changes the active respiratory microbiota, characterized by reduced alpha-diversity, and significantly lower microbial diversity (113). Resultantly, gut microbiota dysbiosis was observed to cause elevated levels of opportunistic pathogens, Streptococcus, Rothia, Veillonella, Actinomyces and a decreased number of beneficial symbionts, Blautia, Rombontsia, Collinsella, and Bifidobacterium (116).…”

“…Later study also demonstrated a disproportionate increase in TNF-a production and cytotoxic function from CD4+ T cells. Not only do these microbes increase the disease severity, but they also offer some degree of protection against SARS-CoV-2, wherein patients showed significantly reduced relative abundance of Bifidobacterium, bacteria used in probiotics (113). By regulating crucial immunological processes, such as dampening the impact of TNF-a, and boosting the Treg responses, they augment the defence against infection (121).…”