Effect of probiotics as an immune modulator for the management of COVID-19

Abstract

COVID-19, an acute respiratory viral infection conveyed by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of individuals globally, and is a public health emergency of international concern. Till now, there are no highly effective therapies for this infection without vaccination. As they can evolve quickly and cross the strain level easily, these viruses are causing epidemics or pandemics that are allied with more severe clinical diseases. A new approach is needed to improve immunity to confirm the protection against emerging viral infections. Probiotics can modify gut microbial dysbiosis, improve the host immune system, and stimulate immune signaling, increasing systemic immunity. Several probiotic bacterial therapies have been proven to decrease the period of bacterial or viral infections. Superinduction of inflammation, termed cytokine storm, has been directly linked with pneumonia and severe complications of viral respiratory infections. In this case, probiotics as potential immunomodulatory agents can be an appropriate candidate to improve the host's response to respiratory viral infections. During this COVID-19 pandemic, any approach that can induce mucosal and systemic immunity could be helpful. Here, we summarize contexts regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. In addition, the effects of probiotics, their mechanisms on different aspects of immune responses against respiratory viral infection, and their antiviral properties in clinical findings have been described in detail.

Keywords: COVID-19; Clinical trial; Gut–lung axis; Probiotics; Respiratory infection; SARS-CoV-2 viruses.

Fig. 1

Mechanisms of probiotic immunomodulation effects in the intestine to defend against respiratory viral infections. Probiotics (highlighted in green color) can induce immunomodulation by directly and indirectly interacting with the cells lining the intestine. Dendritic cells (DC), which extend their dendrites between these intestinal epithelial cells, can sample and process probiotics, activating innate and adaptive immune responses. These dendritic cells (DCs) are located directly below specialized cells called M cells, which can also engulf probiotics and lead to the maturation of dendritic cells (DCs) and the production of plasma cells from B cells. Moreover, when macrophages and dendritic cells (DCs) in the lamina propria interact with probiotics, they become activated and stimulate natural killer (NK) cells to produce interferon-gamma (IFN-γ) to fight off viruses. Probiotics can also stimulate the expression of antiviral genes through toll-like receptors (TLRs) and the nuclear factor-kappa B (NF-κB) pathway. Ultimately, these activated immune cells can travel through the lymphatic and circulatory systems to reach sites of infection and defend against respiratory viruses

Fig. 2

Probiotic effects associated with COVID-19 virus clearance from the host. (1) Entry of virus in the lungs and emphasis on the associated events: Following nasal inhalation of SARS-CoV-2 enters host cells and attaches to the respiratory tract's epithelium layer, leading to microbial dysbiosis. This triggers the activation of the innate immune system via dendritic cells and macrophages through the production of immune signals and pro-inflammatory cytokines. The release of these pro-inflammatory cytokines stimulates the involvement of macrophages and natural killer cells in engulfing and inhibiting virus particles and infected cells. (2) The interaction of the virus with the gut membrane and emphasis on the events associated with it: The initial spread of viruses through the circulatory system can cause changes in the microbiota of the gut epithelium and increase gut permeability, ultimately leading to an inflammatory immune response. Probiotics interact with the gut's epithelium layer and are detected by intestinal immune cells, which can influence the production of pro-inflammatory cytokines and regulate immune responses in the respiratory tract and gut. The pro-inflammatory cytokines secreted during this process disseminate in the blood circulation and reach the respiratory tract's epithelium layer, via the gut–lung axis, aiding alveolar macrophages and natural killer cells in eliminating the coronavirus. Several strains of probiotics produce these cytokines, enhancing the expression of genes related to the innate immune system, even in the lungs, and altering the lung's immune environment ultimately via producing virus-specific immunoglobulins and cytokines