Lost microbes of COVID-19:Bifidobacterium,Faecalibacteriumdepletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity

Abstract

ObjectiveThe 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.DesignUsing 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.ResultsCompared 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<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.ConclusionWe 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 numberNCT04031469 (PCR−) and 04359836 (PCR+).

RETRACTED: Microbiome-Based Hypothesis on Ivermectin’s Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity

“…belong to the same phylum as a critically important constituent of the gut microbiome and common ingredient of probiotics, Bifidobacterium . Bifidobacterium abundance is known to decrease in SARS-CoV-2-infected subjects, as seen in ours and other studies ( Tao et al, 2020 ; Xu et al, 2020 ; Reinold et al, 2021 ; Yeoh et al, 2021 ; Zuo et al, 2021 ; Hazan et al, 2022b ). We have anecdotally observed, through our clinical experiences pre and post Fecal Microbiota Transplant, that certain bacteria in the same phylum may be able to replace each other’s function.…”

“…Ours and other data also support a protective role of Bifidobacterium in SARS-CoV-2 infection, possibly through these immune functions of Bifidobacterium . Our study and others ( Tao et al, 2020 ; Xu et al, 2020 ; Reinold et al, 2021 ; Yeoh et al, 2021 ; Zuo et al, 2021 ; Hazan et al, 2022b ) show that the gut microbiome, particularly Bifidobacterium levels, relates to positivity and severity of SARS-CoV-2 infection. Tao et al (2020) showed that changes in gut microbiota composition might contribute to SARS-CoV-2-induced production of inflammatory cytokines in the intestine, which may lead to the cytokine storm onset.…”

“…Increased Bifidobacterium levels serve as an important indicator of human health and may promote anti-inflammatory activity (Arboleya et al, 2016;Hughes et al, 2017;Tao et al, 2020). It is interesting to note that these same disorders are key risk factors in severe SARS-CoV-2 infection, and Bifidobacterium abundance is also shown to be low in SARS-CoV-2 infection (Tao et al, 2020;Xu et al, 2020;Reinold et al, 2021;Yeoh et al, 2021;Zuo et al, 2021;Hazan et al, 2022b). Probiotics, which typically contain much Bifidobacterium spp., have been proposed as potentially useful SARS-CoV-2 infection prophylaxis or treatment (Bozkurt and Quigley, 2020;Conte and Toraldo, 2020;Bozkurt and Bilen, 2021;Jabczyk et al, 2021).…”

“…Severity of SARS-CoV-2 has been associated with lower levels of Bifidobacterium (Tao et al, 2020;Xu et al, 2020;Reinold et al, 2021;Yeoh et al, 2021;Zuo et al, 2021;Hazan et al, 2022b). Probiotics have been hypothesized and tested with success for improving SARS-CoV-2 symptoms (Bozkurt and Quigley, 2020;Bozkurt and Bilen, 2021;Khaled, 2021;Khodavirdipour, 2021;Gutiérrez-Castrellón et al, 2022;Khodavirdipour et al, 2022), and they are often enhanced by use with prebiotics (Markowiak and Śliżewska, 2017).…”

Gastrointestinal Involvement in SARS-CoV-2 Infection

“…Patients with severe SARS-CoV-2 infection had significantly lower bacterial diversity, and lower relative abundances of Bifidobacterium, Faecalibacterium, and Roseobacter in the gut microbiome, as well as increased Bacteroides spp. [87]. Thus, during the SARS-CoV-2 pandemic, gut microbiota correction may help to improve population immunity and protect public health [88].…”