SARS-CoV-2, Dysbiosis and Potential Role of Probiotics
The ongoing global pandemic of COVID-19 caused by novel SARS-CoV-2 has been identified as a highly contagious and infectious disease mainly affecting the respiratory system leading to acute and severe respiratory infections and often manifesting as pneumonia [1]. The pathogenesis and clinical spectrum of COVID-19 infection is based on increased production of inflammatory cytokines, leading to lung injury, multi-system failure, and death[2]. Specific anti-viral agents and corticosteroid therapy remain the mainstay for management, control of inflammatory diseases[3] and acute respiratory distress syndrome (ARDS). With large scale vaccine availability seems still seems some time away, it is interesting to comprehensively review the vast evidence supporting the rationale for use of probiotics in the context of COVID-19 infections, in the light of convincing and continuously emerging interrelationship between gut dysbiosis and COVID-19 infections [4]
Gut Dysbiosis and COVID-19 Infections
Despite respiratory distress being a significant symptom of COVID-19, this infection is often associated with some non-classical symptoms affecting the gastrointestinal infection (GIT)[5] and manifesting as diarrhoea and sometimes even as inflammatory bowel disease[6]. It is noteworthy that COVID-19 infected patients who presented with gastrointestinal symptoms had more severe respiratory sequels[7], which might be associated with microbial dysbiosis, where a decline in beneficial microbes Lactobacillus and Bifidobacterium has been reported[8]
Evidence for Use of Probiotics in COVID-19 Infections – Aggregate Perspective
Probiotics seem a novel and rational approach to boost immunity against viral infections: Probiotics are reported to ameliorate virulence of COVID-19 by modulating monocyte chemoattractant protein-1 (MCP-1), which is a SARS-CoV-2 virus linked mediator[9]
Evidence with probiotics in COVID-19 - preclinical and clinical studies: Up to 71 % of patients suffering from COVID-19 are treated with antibiotics[10], of which up to 36 % suffered from diarrhoea, which might be antibiotic-associated diarrhoea and its subsequent dysbiosis[11]. This brings out the need for restoring the colonic flora might attenuate vulnerability to secondary infections, through the use of probiotics[12]
Integrated mucosal immunity, gut-lung cross-talk and role of probiotics: The concept of an integrated mucosal immunological system which was first developed in 1978, suggested that our body's mucosal sites, including oral, respiratory, intestinal, and cervical, function as a unit and a system-wide organ to protect against pathogens. This idea is supported by the fact that any two mucosal sites which share the same embryonic origin are therefore similar structurally and functionally
Also, it is well established that a leaky gut due to dysbiosis may worsen illnesses, including lung morbidities as well as increased chances of infiltration of SARS- CoV-2 into the gut lumen and subsequently, lymphatic system, thus leading to infection at a secondary site and worsening of the severity in COVID-19 [14]. The use of probiotics seems to be a promising treatment option to overcome disease severity in COVID-19 in terms of modulation of this interrelated lung and gut microbiome.
COVID-19 in ICU patients and the Scope of Probiotics: It is speculated in COVID-19 patients that the increased association of organ dysfunction might be associated with ICU induced altered gut microbial diversity[15]. This could likely be due to increased use of antibiotics ICU admitted COVID-19 patients, thus supporting the speculation of the potential benefit of supplementation of probiotics in addition to standard care for restoring the gut microbiome and its consequential homeostasis.
Probiotics bacteriocins role in COVID-19: Certain Lactobacilli and Bifidobacteria produce bacteriocins, peptides with antimicrobial properties targeting energized membrane vesicles to disrupt the proton-motive force. These molecules are effective against a wide range of intestinal bacterial pathogens and viruses.[16] The bacteriocins' activity produced by various probiotic microorganisms [17] might support and assist in the treatment of COVID-19 infections.
Probiotics mucin production and COVID-19: Mucus is an extracellular secretion by mucous membranes lining the body cavities, including respiratory, digestive, and urogenital tracts. It acts as a physical protective barrier with mucins-glycoproteins being the significant component. Latest research brings out strong induction of COVID- 19 viral replication via enterocytes [18], thereby rendering mucin biopolymers as emergent broad-spectrum antiviral agents. [19] Probiotics which promote mucus production in the gut appear to, directly and indirectly, enhance gut immunity, eventually empowering systemic immunity [20]
Deducing the Evidence of Probiotics against COVID-19 infections
Probiotics play their role in combating various diseases by enhancing epithelial barrier function. They possess anti-inflammatory activity; harmonizes gut microbial diversity. Probiotics serve as antagonists for various harmful bacterial strains in the gut, blocking or enhancing multiple signaling pathways and production of metabolites such as short-chain fatty acids (SCFAs) which could attenuate the severity of COVID-19 infections.
In totality, there seems enough evidence to consider use of probiotics as supplemental treatment along with standard care in an endeavor to improve clinical outcomes in COVID-19 patients across various clinical settings4
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References
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