Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples

Pascoal, Lívia Bitencourt; Rodrigues, Patrícia Brito; Genaro, Lívia Moreira; Gomes, Arilson Bernardo dos Santos Pereira; Toledo-Teixeira, Daniel A.; Parise, Pierina Lorencini; Bispo-dos-Santos, Karina; Simeoni, Camila L.; Guimarães, Paula Veri; Buscaratti, Lucas I; Elston, João Gabriel de Angeli; Marques-Souza, Henrique; Martins‐de‐Souza, Daniel; Ayrizono, Maria de Lourdes Setsuko; Velloso, Lı́cio A.; Proença-Módena, José Luiz; Moraes‐Vieira, Pedro M.; Mori, Marcelo Alves Silva; Farias, Alessandro Santos; Vinolo, Marco Aurélio Ramirez; Leal, Raquel Franco

doi:10.1080/19490976.2021.1874740

Cited by 43 publications

(38 citation statements)

References 32 publications

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“…A recent study found that SCFAs do not interfere with SARS-CoV-2 infection in the intestine. 31 Although the SCFA concentrations used in that study were much lower than those used in our experiment, the effects of SCFAs on the airway and intestine may vary.…”

Section: Discussionmentioning

confidence: 70%

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa

Takabayashi

Yoshida

Imoto

et al. 2021

Am J Rhinol�Allergy

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Background Coronavirus disease 2019 (COVID-19) has caused a global pandemic. Higher expression of the virus receptor angiotensin-converting enzyme 2 (ACE2) in the nasal mucosa may be associated with high transmissibility and asymptomatic infection. In COVID-19, the elucidation of the determinants of ACE2 expression at nasal tissue level is crucial. The development of strategies to downregulate ACE2 expression in nasal epithelial cells might reduce transmission and be useful as a novel therapeutic approach. Objective To verify ACE2 expression in the nasal mucosa of patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis with nasal polyp (CRSwNP) and to examine the effects of short-chain fatty acids (SCFAs) on ACE2 expression in airway epithelial cells. Methods We assessed ACE2 expression in the nasal mucosa of control subjects, patients with SAR-JCP, and those with CRSwNP using real-time polymerase chain reaction. We also quantified ACE2 gene expression in cultured airway epithelial cells. Results Although ACE2 expression was greatly increased in a few patients with SAR-JCP during the Japanese cedar pollen season, mean levels were not significantly increased. ACE2 mRNA expression was significantly decreased in nasal polyp tissue from patients with chronic rhinosinusitis compared with the expression in that from control subjects. SCFAs generated by gastrointestinal microbiota significantly reduced resting ACE2 expression in cultured airway epithelial cells. SCFAs also significantly suppressed the dsRNA-dependent upregulation of ACE2 expression in airway epithelial cells. Conclusion Inflammatory endotype affects ACE2 expression in the nasal mucosa and influences susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In particular, type 2 inflammation could downregulate ACE2 expression in the nasal mucosa and reduces susceptibility to SARS-CoV-2 in patients with CRSwNP. Although in vivo experiments are required, administration of SCFAs to the nasal cavity might be worthy of consideration as a preventative or therapeutic strategy for the early-stage COVID-19.

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Section: Discussionmentioning

confidence: 70%

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa

Takabayashi

Yoshida

Imoto

et al. 2021

Am J Rhinol�Allergy

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“…Butyrate (one of the key SCFAs)-producing bacterium is significantly reduced during COVID-19 infection [ 27 , 29 , 31 , 35 , 53 ]. The resulting reduction of butyrate production in the gut may be linked to a pro-inflammatory state [ 54 ], thus increasing susceptibility to pulmonary viral infections, including COVID-19 [ 55 – 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…The resulting reduction of butyrate production in the gut may be linked to a pro-inflammatory state [ 54 ], thus increasing susceptibility to pulmonary viral infections, including COVID-19 [ 55 – 57 ]. Although evidence suggests that SCFA does not interfere with COVID-19 infection in the intestine [ 53 ], a reduction in SCFA may promote a systemic pro-inflammatory state in both macaques [ 52 ] and humans [ 58 ]. In support of this, dietary interventions may alter the composition of airway and intestinal microbiota, which may potentially affect the clinical course of COVID-19 infection by modulating systemic immune responses [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review

et al. 2021

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“…COVID-19 patients showed significant dysbiosis of the fecal microbiome, which was characterized by an enrichment of opportunistic pathogens and a depletion of beneficial commensals [ 19 ]. Numerous experimental and clinical observations suggested that the gut microbiota plays a key role in the pathogenesis of sepsis and acute respiratory distress syndrome, suggesting that SARS-CoV2 might also have an impact on the gut microbiota and vice-versa [ 41 , 42 , 43 ]. Our results showed that serum and fecal total IgA levels were substantially higher in the COVID-19 IgAN case than in healthy controls, as were the levels of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

Zhang

Guo

et al. 2021

Pathogens

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The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4–41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

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Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples

Cited by 43 publications

References 32 publications

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

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