How Gut Microbes Affect Immune Responses to SARS-CoV-2

Articles published in Critical Review of Food Science and Nutrition The journal provides an overview of the role of the gut microbiota in shaping host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

study: Gut microbiota and antiviral immunity in COVID-19Image credit: Design_Cells / Shutterstock

Background

SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, is an RNA virus that primarily affects the upper and lower respiratory tract. The virus is also known to potentially target the gastrointestinal (GI) tract and impair gut microbiota composition and diversity.

The gut flora is the collection of microorganisms that naturally inhabit the digestive tract. The digestive tract contains trillions of microorganisms that interact with each other to regulate various physiological processes, including the immune system. Alterations in gut microbiota composition and diversity are termed dysbiosis, which impair immune responses and inflammation.

Gut microbiota and COVID-19

Gastrointestinal symptoms such as nausea, vomiting and diarrhea have been observed in 60% of COVID-19 patients. Impaired gut microbiota has been observed in COVID-19 patients with or without gastrointestinal symptoms. Importantly, it has been observed that gut microbiota persists for up to 6 months after SARS-CoV-2 is clinically cleared from the respiratory tract.

Altered gut microbiota commonly observed in COVID-19 patients include a reduction in commensal bacterial populations with immunomodulatory functions that help maintain the integrity of the gut barrier and immune homeostasis .

A significant proportion of COVID-19 patients develop long-term symptoms medically termed long-term COVID. Studies have shown that people with long-term COVID-19 have reduced commensal bacterial populations and altered overall gut microbiota. Moreover, decreased bacterial counts correlate with increased serum concentrations of pro-inflammatory mediators in these patients.

A decrease in commensal bacterial populations is accompanied by an enrichment of pathogenic bacterial populations and a decrease in gut microbiota diversity. Studies suggest that these changes in gut microbiota composition and diversity may be associated with increased intestinal permeability, microbial migration, hyperinflammation and poor prognosis in COVID-19 doing.

In addition to bacterial populations, SARS-CoV-2 infection is known to alter intestinal fungal populations. Concentrations of opportunistic fungal pathogens have been observed in COVID-19 patients. Pathogens such as these are associated with pneumonia and respiratory symptoms and affect gut bacterial populations.

Gut microbiota and SARS-CoV-2 host cell invasion

spike glycoprotein SARS-CoV-2 interacts with the host cell membrane receptor angiotensin-converting enzyme 2 (ACE2) to initiate the viral entry process. In addition to respiratory epithelial cells, ACE2 was expressed at high levels in the stomach, ileum, and colon, highlighting the possibility of direct virus entry into the gastrointestinal tract.

The abundance of specific bacterial species that downregulate ACE2 expression is known to be negatively correlated with COVID-19 severity. Patients with diabetes or obesity have lower levels of these bacteria and are at highest risk of COVID-19-related death.

Gut microbiota and immune responses to SARS-CoV-2 infection

The gut microbiota is known to stimulate host antiviral immune responses by modulating type 1 interferon signaling. Impaired interferon responses and suppressed adaptive immune responses are known to cause lung injury in her COVID-19 patients with severe disease. Alterations in the gut microbiota by SARS-CoV-2 may be relevant to these pathologies.

The inflammasome, a cytoplasmic multiprotein complex, is known to be involved in the pathogenesis of COVID-19. Recent evidence suggests that the inflammasome induced the release of neutrophil extracellular traps by neutrophils in severe her COVID-19 patients, which is associated with impaired lung function.

Altered gut microbiota may contribute to the pathogenesis of COVID-19 by triggering inflammasome activation. For example, in her COVID-19 patients with heart disease, increased inflammasome activation and elevated markers of leaky gut, such as lipopolysaccharide-binding protein, have been observed.

The gut microbiota is essential for the regulation of the adaptive immune system. For example, in response to viral infection, the gut microbiota induces activation of her B cells, T cellsthus involved in antibody production and virus-specific memory immune cell production.

Administration of certain commensal bacteria has been shown to increase neutralizing antibody levels in the blood in response to viral vaccination. Similar effects have been observed in COVID-19 patients.

enteropulmonary immune axis

The gut microbiota plays an important role in regulating lung health. Immune cells travel from the intestine to the respiratory tract and destroy invading pathogens. This is called the enteropulmonary immune axis.

Changes in the composition of the gut microbiota increase the risk of respiratory diseases such as asthma. Opportunistic upper respiratory tract bacteria have been identified in the gut microbiota in COVID-19 patients. Similarly, an imbalance in gut microbiota has been observed in COVID-19 patients. These observations highlight the occurrence of microbial bidirectional translocation between the gut and lung.

Modulation of gut microbiota as a therapeutic intervention for COVID-19

Given the significant association between gut microbiota disorders and anti-SARS-CoV-2 immune responses, we considered that gut microbiota modulation could be a potential therapeutic intervention for COVID-19. It has been taken.

Transplantation of the fecal microbiota, representing the entire gut microbiota, from a healthy donor into the recipient gastrointestinal tract is considered a potential strategy for treating bacterial infections. This strategy is currently under clinical investigation in COVID-19 patients.

Edible prebiotics are non-digestible fibers used to increase the proportion of commensal bacteria and decrease the proportion of pathogenic bacteria. Evidence suggests health benefits of prebiotics in COVID-19 patients.

Probiotics are live organisms that have immunomodulatory effects. Furthermore, peptides produced by probiotics have shown ACE2 inhibitory effects. Probiotics are therefore considered a potential adjuvant strategy in the treatment of COVID-19 patients.