How the Gut Microbiome Affects COVID-19 Severity

As of September 27, 2022, the coronavirus disease 2019 (COVID-19) has killed more than 6.5 million people worldwide. COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was remarkably unpredictable in its clinical severity.

As a result, many efforts have been made to identify factors that increase an individual’s risk of severe or fatal COVID-19.Recent Pathogen A journal study reviews the potential role of the gut microbiota in determining severe COVID-19.

study: The Gut Microbiome and COVID-19: Potential Impact on Disease Severity. Image credit: nobeastsofierce / Shutterstock.com

prologue

Previous studies have highlighted the importance of the gut microbiota in regulating inflammatory processes at both local and systemic levels. The microbiome is also called the body’s “second brain” because it communicates extensively with other organs and systems in the body.

The risk of enterobacteriosis has been shown to increase during SARS-CoV-2 infection and during acute COVID sequelae (PASC), the latter more commonly known as ‘prolonged COVID’. . In these situations, increased concentrations of opportunistic pathogenic species have been reported, while numbers of ‘good’ bacteria have decreased. However, the reverse was also true, and patients with fewer bowel symptoms were less likely to experience clinical deterioration.

Dysbiosis causes inflammation

SARS-CoV-2 gains entry into target host cells by binding to receptor binding domains (RBDs) within the virus. spike protein S1 subunit to angiotensin-converting enzyme 2 (ACE2) receptor.

The ACE2 receptor is renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure. Therefore, downregulation of her ACE2 during SARS-CoV-2 infection may affect RAAS function.

of cytokine stormis characterized by excessive release of cytokines and commonly occurs in severe COVID-19. This occurs following detection of infected cells by innate immune cells and subsequently triggers a hyperinflammatory immune response. Cytokines release proinflammatory messenger molecules such as interleukin-1 (IL-1), IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Releases in high concentrations. level to circulation.

Cytokine storm induces systemic vasodilation, increases vascular permeability, and causes thrombotic complications, pulmonary edema, and multiple organ failure. When these occur in people with cardiovascular disease or other risk factors for thrombosis, severe and fatal outcomes are more likely to occur. ARDS).

Dysbiosis causes systemic effects

About 1 in 5 people with COVID-19 will develop diarrhea with or without abdominal discomfort or pain at some point during the infection. Viral RNA appears to persist in the intestinal mucosa and stool of previously infected patients more than 1 month after the onset of symptoms. SARS-CoV-2 can not only damage enterocytes directly, but also cause intestinal injury through this inflammatory environment.

Some COVID-19 patients with diarrhea exhibit higher serum cytokine levels, possibly due to viral proteins binding to epithelial cell proteins that help form tight junctions. The resulting disruption of the intestinal epithelial barrier disrupts intracellular ionic balance, leading to colitis and an inflamed intestinal wall. Furthermore, this may allow gut bacteria to enter the systemic circulation and contribute to immune-mediated inflammatory damage throughout the body.

High expression of ACE2 in the intestinal epithelium is key to ensuring stable and healthy microbiome composition and function. Conversely, decreased ACE2 expression also decreases sodium and amino acid uptake, thus increasing susceptibility to intestinal inflammation.

Decreased ACE2 expression in the intestinal epithelium attenuates the target of the mammalian rapamycin (mTOR) pathway and alters antimicrobial peptide (AMP) expression with increased autophagy. Interference with these interacting processes compromises enterocyte survival.

A weakened intestinal barrier results in chronic intestinal dysfunction and altered absorption of amino acids such as phenylalanine, tryptophan, glutamine, and leucine. may be connected.

Enterobacteriosis increases vulnerability to respiratory infections and their clinical severity. For example, mice with antibiotic-induced gut microbiota are more susceptible to influenza-induced lung inflammation.

Gut microbiome increases severity of COVID-19

Several previous studies have shown that COVID-19 is likely to be less severe, especially when the abundance of seven bacterial classes is increasing. Faecalibacterium prausnitzii When Aristipes OnderdonkyBoth of these microbial species regulate tryptophan metabolism and immune homeostasis. Faecalibacterium prausnitzii Western diets often have lower levels, while Mediterranean diets have higher levels.

Severe COVID-19 is Coprobacillus, Clostridium ramossumC.HathawayWhen Erysiperotrichaceae. In addition, Coprobacillus It is highly correlated with diarrhea and inflammation in irritable bowel disease (IBD).

especially of some species bacteroides Reduces ACE2 expression in rat colon and is associated with less severe COVID-19.

Bacterial metabolites such as short-chain fatty acids (SCFAs) derived from bacterial fermentation of dietary fiber may also be involved in homeostasis. Butyrate is particularly important as it maintains the integrity of the intestinal epithelial barrier while regulating immune and inflammatory pathways throughout the body.

SCFAs also work in many other ways to reduce inflammation. For example, gut microbiota dysbiosis reduces SCFA production by reducing associated bacterial taxa while promoting opportunistic pathogen abundance. These microbes can penetrate the weakened intestinal mucosal barrier and then cause secondary infections in already vulnerable individuals, increasing the risk of severe or fatal outcomes.

COVID-19 causes dysbiosis

In COVID-19 patients, the gut microbiome is altered with fewer commensal bacteria of key species. bacteroides,beneficial LachnospiraceaeWhen bifidobacteriaAt the same time, opportunistic pathogens like Streptococcus, Lotia, and some species Clostridium favorite C. Hathaway gain.

Increased signs of inflammation such as C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), circulating IL-6, IL-10, IFN-γ, and TNF-α levels has also been reported. These changes persisted even 1 month after viral clearance.

Probiotics reduce the severity of COVID-19

Probiotics, especially those containing bifidobacteria Seeds shorten upper respiratory tract infections through anti-inflammatory effects mediated by modulation of the gut microbiota. Studies therefore show that probiotic supplementation can reduce the severity of COVID-19.

Previously, probiotics increased virus-specific immunoglobulin M (IgM) and IgG without causing major changes in fecal microbiota profiles. This was not due to changes in the composition of the gut microbiota, indicating a direct effect of her IgG on immunity.

ACE and COVID-19 severity

Several studies have found that patients with pre-existing lung disease, cancer, solid transplantation, older age (>70 years), obesity, cardiovascular disease, and metabolic syndrome are at increased risk of severe and fatal COVID-19. has been identified. This may be due to changes in her ACE2 activity, including RAAS. For example, patients with lung cancer and diabetes express her ACE2 at higher baseline levels.

SARS-CoV-2 infection causes increased ACE2 expression in the lung and kidney, especially in elderly patients and those with chronic lung disease, diabetes, and hypertension. This may lead to excessive activation of the ACE-angiotensin II-angiotensin 1 receptor axis.

Consequences of these activities include vascular damage and dysfunction, pulmonary and myocardial inflammation and fibrosis, kidney damage, and insulin resistance due to increased oxidative stress.

Dysregulation of ACE-2 by infection, comorbidities, involvement of gut microbiota alterations during COVID-19, and beneficial effects of dietary supplements in restoring microbiota and immune homeostasis.

Nutrition and COVID-19

Obese individuals have chronic low-grade inflammation with visceral fat deposits and high levels of inflammatory mediators produced by innate immune cells. This increases the risk of cytokine storm after viral infection, exacerbated by concomitant gut microbiota and pressure on the lungs.

East Asian countries that primarily consume rice report much lower death rates from COVID-19 than other wheat-eating countries in the world.

Vitamin D modulates T-cell function, decreases inflammatory mediators, and increases anti-inflammatory molecules such as IL-10 and their effects on innate immune function. Vitamin D supplementation may reduce the risk of severe infection and death associated with COVID-19.

Vitamins C, E, A, and metals such as zinc and iron are powerful anti-inflammatory and antioxidant compounds that work through different pathways. Maintaining a 1:5 ratio of each is a potentially important safeguard. Overall, a plant-based diet enriched with functional foods and supplements can help protect against respiratory infections.

Conclusion

The composition of the gut microbiota largely determines how the immune system responds to multiple pathogens, including SARS-CoV-2. In addition, dysbiosis can be considered a risk factor and consequence of her severe COVID-19.

It is clear that interventions aimed at re-establishing the correct microbiota composition are important for developing a more holistic approach to managing a range of diseases, including COVID-19.….Strategies aimed at lifestyle and dietary modifications can positively modulate the gut microbiota and help play a preventative role in SARS-CoV-2 viral infection”