Probiotics in Prevention and Treatment of COVID-19: Review of Latest Evidence

Gut Dysbiosis correlated with COVID-19 infections and its Severity

Five studies directly connect microbiota with COVID- 19, supporting the presumptive role of probiotics in both prevention and treatment of COVID-19. A study sequencing faecal samples of patients reported that COVID-19 infections significantly modified faecal microbiomes marked by a decline in beneficial commensals and enrichment of opportunistic pathogens[2]. The baseline abundance of Coprobacillus and few Clostridium species have correlated with the severity of COVID-19. The abundance of Faecalibacterium prausnitzii, an anti-inflammatory bacterium, inversely correlated to COVID-19 severity, demonstrating the influence of SARS-CoV-2 on gut microbiome. Along similar lines, Yeoh YK, et al, reported significant alterations in the gut microbiome and dysbiosis in COVID 19 patients, associated with disease severity and inflammatory markers.[3] The continuously evolving evidence supports the potential role of microbiota in the susceptibility, progression, and severity of COVID-19.[4]

Immunomodulatory Activity of Probiotics: Beyond the Gut

Although the mechanism of action of probiotics profoundly focuses on the GIT, the effect of probiotics is not confined to the initial infection site. They can act on the entire body via immune modulation. Probiotics and their antigenic metabolites are phagocytosed by microfold cells to form endosomes in gut-associated lymphoid tissues. These antigens are suddenly released and taken in by dendritic cells (DCs), which can transport them to local lymph nodes and consequently activate naive T and B cells to differentiate into diverse effector subpopulations. This cascade subsequently, initiates the release of relevant cytokines and various immune responses[5]

Probiotics such as Lactobacillus have the ability to restore host health by eliminating pathogens and regulating immune responses in intestinal epithelial cells. Probiotics stimulate the immune system, thus increase immunoglobulins (Igs) generation, enhance macrophage and lymphocyte activity, and interferon (IFN)- ɤ stimulation[6]. Probiotics may also attenuate exaggerated immune responses, primarily through their anti-inflammatory activities[7].

Rationale for consideration of probiotics in the management of COVID-19

Dysbiosis predisposes an individual to abnormal inflammatory status and increases the susceptibility to disease. Probiotic supplementation helps to maintain symbiosis in the GIT and thereby modulate the immune system. The symbiotic state helps to control the severity of COVID-19 via the gut-lung and gut-brain axes. Probiotics can modulate innate and adaptive immune responses, control the synthesis of immunoglobulins, inhibit various cytokines and chemokines, express several virus defence genes and regulate T helper (Th1, Th2, Treg) cells.[7]

Up to 71% of COVID-19 patients are administered antibiotics as reported in some countries, and diarrhoea was reported in up to 36% of them. Reinforcement of colonic microflora using probiotics diminishes secondary infection and diarrhoea in patients receiving antibiotics.

Probiotics in Respiratory Infections and COVID-19: Review of Evidence

A scientific report from Asia showed that COVID-19 patients suffer microbial dysbiosis with depleted Lactobacillus and Bifidobacterium in their gut, and about 60% of these patients express gastrointestinal symptoms such as diarrhoea, nausea, and vomiting[8]. The gastrointestinal symptoms also imply greater severity of COVID-19 infection. A meta-analysis published by Kang EJ, et al. revealed that probiotics such as Lactobacillus and Bifidobacterium led to a decrease in respiratory symptoms, which are invariably, also a symptom of SARS-CoV-2 infection[9]. A meta-analysis of RCTs suggests that probiotics decreased ventilator-associated pneumonia (VAP) [10] and reduced the duration of antibiotic use for VAP thus bringing out their therapeutic opportunity for their consideration to improve clinical outcomes in COVID-19.

Take-Home Considerations

Evidence supports the role of probiotics in regulating the immune system, suggesting a definitive role for probiotics in viral infections. Probiotics supplementation could reduce the severity of COVID-19 morbidity and mortality. They may be able to inhibit cytokine storm by simultaneously boosting innate immunity and evading the exaggeration of adaptive immunity, which is often challenged to respond rapidly and aggressively to the viral onslaught. Probiotics-induced suppression of inflammatory cytokine response may prevent both the severity and the occurrence of Acute Respiratory Distress Syndrome (ARDS), making probiotics an attractive adjunct.

Rediscovering and repurposing effective therapies could help to positively impact the course of the pandemic, clinical outcomes of COVID-19, and the lives of the affected population across the globe. Considering utilisation of probiotics in high risk and severely ill patients and frontline health workers might be a noteworthy therapeutic option to limit the infection and may help flatten the COVID-19 curve.[7]

References

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