State of the Intestinal Microbiome and COVID-19 Infection − Possible Correlations
Some patients infected with the SARS-CoV-2 virus exhibit gastrointestinal symptoms, including diarrhea, during the course of COVID-19. Current knowledge suggests that COVID-19 symptoms are related, among other things, to the intestinal microbiome. Could the use of probiotics therefore act as a prevention of this disease or its more severe course?
The “gut − lung” axis and the influence of the intestinal microbiome on the respiratory tract
The action of bacterial enzymes in the ascending colon produces short-chain fatty acids (SCFA). These can be transported (not only) to the lungs via the bloodstream, where they have anti-inflammatory effects. Thus, the intestinal microbiome likely has a protective effect against respiratory tract (RT) infections. It appears that inflammation in this area may subsequently affect the diversity of the intestinal microflora.
The SARS-CoV-2 virus uses the angiotensin-converting enzyme (ACE2) as a receptor to enter target cells. This enzyme is expressed not only by epithelial cells of the lungs but also by those of the intestines. This may be related to the less common gastrointestinal symptoms of COVID-19. In some patients, the virus has been detected in the stool, suggesting it can also spread via the fecal-oral route. Up to 50% of these patients continued to excrete the virus even with negative nasopharyngeal swabs.
The stool analysis of 15 COVID-19+ patients showed a positive correlation between the high presence of bacterial species Coprobacillus, Clostridium ramosum, and Clostridium hathewayi and the severity of the disease. In contrast, lower prevalence was noted for Faecalibacterium prausnitzii and Alistipes onderdonkii. Among 11 patients, stool samples were positive at hospital admission, with 6 samples remaining positive at discharge. Overall, 14 bacterial species, including Bacteroides dorei, B. thetaiotaomicron, and B. massiliensis, were associated with viral load in the stool. Bacteroides ovatus, which downregulates ACE2, showed an inverse correlation, while Erysipelotrichaceae bacterium had a positive correlation. The results further suggest that intestinal dysbiosis persists even in remission.
Polypharmacy as a risk factor for severe COVID-19?
Available data indicate that comorbidities such as type 2 diabetes mellitus, obesity, atherosclerosis, or hypertension are often associated with a more severe course of COVID-19 and consequently, higher mortality. The pro-inflammatory state and polypharmacy, which are common especially in older patients, are related, among other things, to lower intestinal microflora diversity and greater susceptibility to infections.
The use of medications such as laxatives, proton pump inhibitors, metformin, or antibiotics (ATB) particularly impacts the intestinal microbiome (e.g., reduced prevalence of the genus Bifidobacterium). Concerning ATB, resistance to macrolides (azithromycin), which COVID+ patients use to treat bacterial superinfection of the RT, is particularly problematic. Additionally, corticosteroids (dexamethasone) or nonsteroidal anti-inflammatory drugs, which can also induce intestinal dysbiosis, must be mentioned. On the other hand, antivirals (remdesivir) and paracetamol were shown to be harmless in this respect. However, intestinal dysmicrobia increases the absorption and bioavailability of paracetamol, thus the risk of hepatotoxicity. There was also a demonstrated association between the intestinal microbiome and vitamin D levels.
Conclusion
Probiotics and prebiotics are thus suggested for preventive measures against COVID-19 and as supportive treatments. Studies have shown that their use reduces the risk of (rhino)viral RT infection in prematurely born children. Other authors report accelerated recovery from acute respiratory infections (flu) in adults who use probiotics (containing the genera Lactobacillus and Bifidobacterium). Probiotic use is also associated with a reduced need for mechanical ventilation in critically ill COVID-19-positive patients in intensive care.
A low-fat diet high in fiber and starch, which supports SCFA production, should also be the norm. It is advisable to limit pro-inflammatory red meat and alcohol and increase the intake of anti-inflammatory substances from fruits, vegetables, and fish.
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Source: Donati Zeppa S., Agostini D., Piccoli G. et al. Gut microbiota status in COVID-19: an unrecognized player? Front Cell Infect Microbiol 2020; 10: 576551, doi: 10.3389/fcimb.2020.576551.
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