Could Perturbation of Gut Microbiota Possibly Exacerbate the Severity of COVID-19 via Cytokine Storm?

Vignesh, Ramachandran; Swathirajan, Chinnambedu Ravichandran; Tun, Zaw Htet; Rameshkumar, Marimuthu Ragavan; Solomon, Sunil S.; Balakrishnan, Pachamuthu

doi:10.3389/fimmu.2020.607734

Cited by 57 publications

(65 citation statements)

References 93 publications

(107 reference statements)

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“…In fact, the presence of circulating LPS induces toll-like-receptor 4 activation and the production of host response molecules such as LBP and the consumption of neutralizing antibodies against LPS endotoxin core antigen as well as the activation of the inflammatory host defence via binding to soluble CD14, which, in turn, initiates the production of several cytokines ( 9 , 28 ). Furthermore, IL-6 mediated vascular damage may also contribute to increase intestinal permeability, precipitate microbial translocation and perpetuate systemic inflammation ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19

et al. 2021

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Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March–July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.

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Section: Discussionmentioning

confidence: 99%

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19

et al. 2021

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“…It was previously postulated that perturbations in gut microbiota and microbial translocation may exacerbate the severity of cytokine storm in COVID-19 (30).…”

Section: Discussionmentioning

confidence: 99%

Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients

Teixeira

Dorneles

Filho

et al. 2021

Preprint

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This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations, and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients.

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“…This may be caused by a plethora of factors including aging and is associated with the pathogenesis of various diseases (Donati Zeppa et al, 2020). Various studies demonstrating the role of gut dysbiosis in aging-related cardiovascular, metabolic, and renal disorders, correlates with the increased severity of COVID-19 observed in patients with these pre-existing conditions (Chiappetta et al, 2020;Sanchez-Rodriguez et al, 2020;Vignesh et al, 2021). A recent fecal metabolomic study demonstrated the possible link between the gut microbiota and inflammatory responses leading to severe COVID-19 manifestations.…”

Section: The Possible Role Of Gut Dysbiosis and Associated Leaky Gutmentioning

confidence: 99%

“…Besides, in the pathogenesis of severe COVID-19, there is also an implication of the cross-talk between the gut barrier and lung through the gut-lung axis (Openshaw, 2009;Vignesh et al, 2021).…”

Section: Foraying Through the Eye Of Cytokine Stormmentioning

confidence: 99%

“…Also, significantly higher titers of IgA with potent neutralizing ability have been observed among COVID-19 patients with gastrointestinal symptoms indicating the key role of IgA (Wang et al, 2021). With mounting evidence from studies demonstrating the cross-talk between the lungs and gut microbiota, secretory IgA could be a significant mediator of this 'gut-lung axis' (Sencio et al, 2021;Vignesh et al, 2021).…”

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confidence: 99%

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Could Nutraceutical Approaches Possibly Attenuate the Cytokine Storm in COVID-19 Patients?

Vignesh

Velu

Sureban

2021

Front. Cell. Infect. Microbiol.

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Could Perturbation of Gut Microbiota Possibly Exacerbate the Severity of COVID-19 via Cytokine Storm?

Cited by 57 publications

References 93 publications

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19

Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients

Could Nutraceutical Approaches Possibly Attenuate the Cytokine Storm in COVID-19 Patients?

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