SARS‐CoV‐2 triggered oxidative stress and abnormal energy metabolism in gut microbiota

Zhou, Tuoyu; Wu, Jingyuan; Zeng, Yufei; Li, Junfeng; Yan, Jun; Meng, Wenbo; Han, Huawen; Feng, Fengya; He, Jufang; Zhao, Shuai; Zhou, Ping; Wu, Ying; Yang, Yanlin; Han, Richou; Jin, Wei‐Lin; Li, Xun; Yang, Yunfeng; Li, Xiangkai

doi:10.1002/mco2.112

Cited by 23 publications

(26 citation statements)

References 82 publications

(214 reference statements)

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“…In a small study comparing COVID-19 patients to controls, a decrease in Prevotella copri abundance was noted, however, a positive association with viral load of SARS-CoV-2 in the upper respiratory tract was also identified. Moreover, the same study found an increase in E.coli in COVID-19 patients, and a positive correlation with COVID-19 severity (Zhou et al, 2022), which is supported by the PERMANOVA in this study. Though E.coli are a commensal member of the gut microbiota, there are multiple well known pathogenic subspecies which may alter different cellular processes (Kaper et al, 2004).…”

Section: Discussionsupporting

confidence: 87%

COVID-19 severity is associated with population-level gut microbiome variations

Lymberopoulos

Gentili

Budhdeo

et al. 2022

Front. Cell. Infect. Microbiol.

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The human gut microbiome interacts with many diseases, with recent small studies suggesting a link with COVID-19 severity. Exploring this association at the population-level may provide novel insights and help to explain differences in COVID-19 severity between countries. We explore whether there is an association between the gut microbiome of people within different countries and the severity of COVID-19, measured as hospitalisation rate. We use data from the large (n = 3,055) open-access gut microbiome repository curatedMetagenomicData, as well as demographic and country-level metadata. Twelve countries were placed into two groups (high/low) according to COVID-19 hospitalisation rate before December 2020 (ourworldindata.com). We use an unsupervised machine learning method, Topological Data Analysis (TDA). This method analyses both the local geometry and global topology of a high-dimensional dataset, making it particularly suitable for population-level microbiome data. We report an association of distinct baseline population-level gut microbiome signatures with COVID-19 severity. This was found both with a PERMANOVA, as well as with TDA. Specifically, it suggests an association of anti-inflammatory bacteria, including Bifidobacteria species and Eubacterium rectale, with lower severity, and pro-inflammatory bacteria such as Prevotella copri with higher severity. This study also reports a significant impact of country-level confounders, specifically of the proportion of over 70-year-olds in the population, GDP, and human development index. Further interventional studies should examine whether these relationships are causal, as well as considering the contribution of other variables such as genetics, lifestyle, policy, and healthcare system. The results of this study support the value of a population-level association design in microbiome research in general and for the microbiome-COVID-19 relationship, in particular. Finally, this research underscores the potential of TDA for microbiome studies, and in identifying novel associations.

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Section: Discussionsupporting

confidence: 87%

COVID-19 severity is associated with population-level gut microbiome variations

Lymberopoulos

Gentili

Budhdeo

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Immunonutrition has been shown to exert pleiotropic actions on the intestinal mucosa, including proliferative, antiapoptotic, antioxidant and anti-inflammatory effects, thus enhancing the mechanical (enterocytes and tight junctions) and immunological integrity of the gut barrier and preventing bacterial translocation [ 85 , 86 , 87 ]. In addition, previous studies have shown that the altered microbiota composition in COVID-19 is a source of high oxidative stress which may injure the intestinal epithelium [ 88 ]. Therefore, antioxidant treatments including α-tocopherol, ascorbic acid, allopurinol and N-acetyl-cysteine might have a positive impact on the mechanical barrier integrity through prevention of oxidative stress-induced apoptosis of enterocytes or TJs’ disruption [ 89 ].…”

Section: Therapeutic Approaches Targeting the Gut Barriermentioning

confidence: 99%

SARS CoV-2-Induced Viral Sepsis: The Role of Gut Barrier Dysfunction

et al. 2022

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A considerable proportion of patients with severe COVID-19 meet Sepsis-3 criteria and share common pathophysiological mechanisms of multiorgan injury with bacterial sepsis, in absence of secondary bacterial infections, a process characterized as “viral sepsis”. The intestinal barrier exerts a central role in the pathophysiological sequence of events that lead from SARS-CoV-2 infection to severe systemic complications. Accumulating evidence suggests that SARS-CoV-2 disrupts the integrity of the biological, mechanical and immunological gut barrier. Specifically, microbiota diversity and beneficial bacteria population are reduced, concurrently with overgrowth of pathogenic bacteria (dysbiosis). Enterocytes’ tight junctions (TJs) are disrupted, and the apoptotic death of intestinal epithelial cells is increased leading to increased gut permeability. In addition, mucosal CD4(+) and CD8(+) T cells, Th17 cells, neutrophils, dendritic cells and macrophages are activated, and T-regulatory cells are decreased, thus promoting an overactivated immune response, which further injures the intestinal epithelium. This dysfunctional gut barrier in SARS-CoV-2 infection permits the escape of luminal bacteria, fungi and endotoxin to normally sterile extraintestinal sites and the systemic circulation. Pre-existing gut barrier dysfunction and endotoxemia in patients with comorbidities including cardiovascular disease, obesity, diabetes and immunosuppression predisposes to aggravated endotoxemia. Bacterial and endotoxin translocation promote the systemic inflammation and immune activation, which characterize the SARS-CoV-2 induced “viral sepsis” syndrome associated with multisystemic complications of severe COVID-19.

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“…Furthermore, recently published studies also show secondary bacterial infection and bacterial translocation among 12–14% of COVID-19 patients ( 74 , 75 ). Decreased microbial richness and microbial dysbiosis observed in COVID-19 patients may persist for a long duration even after recovery and respiratory clearance of the virus ( 22 , 73 , 76 ). Contrary to that, another study with a majority African American cohort reveals that dysbiotic gut microbial composition is restored back to uninfected status upon recovery ( 77 ).…”

Section: Gut Microbial Alterations In Oud and Sars-cov-2 Infectionmentioning

confidence: 99%

“…On the other hand, the level of metabolites that are known to exhibit immunosuppressive and anti-inflammatory effects such as D-allose and D-arabinose were found to be depleted in patient fecal samples ( 79 ). Metagenomic and meta-transcriptomic data reveal significant depletion of short chain fatty acid (SCFA) producing bacterial taxa Ruminococcaceae and Clostridiaceae ( 19 ) and decreased activity of butyrate-producing bacteria, which is reflected in the reduced SCFAs levels observed in fecal samples of COVID-19 patients ( 73 , 82 ). Depletion of SCFA synthesis pathways was associated with disease severity and showed persistent depletion in patients even after viral clearance ( 82 ).…”

Section: Gut Microbial Alterations In Oud and Sars-cov-2 Infectionmentioning

confidence: 99%

Opioid-Use, COVID-19 Infection, and Their Neurological Implications

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an imminent threat to human health and public safety. ACE2 and transmembrane serine protease 2 proteins on host cells provide the viral entry point to SARS-CoV-2. Although SARS-CoV-2 mainly infects the respiratory system, there have been reports of viral neurotropism and central nervous system injury as indicated by plasma biomarkers, including neurofilament light chain protein and glial fibrillary acidic protein. Even with a small proportion of infections leading to neurological manifestation, the overall number remains high. Common neurological manifestations of SARS-CoV-2 infection include anosmia, ageusia, encephalopathy, and stroke, which are not restricted to only the most severe infection cases. Opioids and opioid antagonists bind to the ACE2 receptor and thereby have been hypothesized to have therapeutic potential in treating COVID-19. However, in the case of other neurotropic viral infections such as human immunodeficiency virus (HIV), opioid use has been established to exacerbate HIV-mediated central nervous system pathogenesis. An analysis of electronic health record data from more than 73 million patients shows that people with Substance Use Disorders are at higher risk of contracting COVID-19 and suffer worse consequences then non-users. Our in-vivo and in-vitro unpublished studies show that morphine treatment causes increased expression of ACE2 in murine lung and brain tissue as early as 24 h post treatment. At the same time, we also observed morphine and lipopolysaccharides treatment lead to a synergistic increase in ACE2 expression in the microglial cell line, SIM-A9. This data suggests that opioid treatment may potentially increase neurotropism of SARS-CoV-2 infection. We have previously shown that opioids induce gut microbial dysbiosis. Similarly, gut microbiome alterations have been reported with SARS-CoV-2 infection and may play a role in predicting COVID-19 disease severity. However, there are no studies thus far linking opioid-mediated dysbiosis with the severity of neuron-specific COVID-19 infection.

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SARS‐CoV‐2 triggered oxidative stress and abnormal energy metabolism in gut microbiota

Cited by 23 publications

References 82 publications

COVID-19 severity is associated with population-level gut microbiome variations

COVID-19 severity is associated with population-level gut microbiome variations

SARS CoV-2-Induced Viral Sepsis: The Role of Gut Barrier Dysfunction

Opioid-Use, COVID-19 Infection, and Their Neurological Implications

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