The intestinal microbiota influences the balance between pro-inflammatory and regulatory responses and shapes the host’s immune system
Our immune system is a system of cells and tissue that protects the individual from invading pathogens, while at the same time providing tolerance to diet-based animal and plant materials, non-threatening organisms (i.e. our microbiota) and the self.
For the immune system to function properly, it needs to be exposed to antigens from food and microorganisms. The status of our defenses are also closely related to the host’s nutritional status. In other words, an appropriate nutritional status means the organism’s defenses work properly, while, conversely, certain physiological (e.g. aging and sports requiring low body weight, such as elite gymnastics) and pathological situations (e.g. obesity and eating disorders) may trigger immune function impairment.
The immune system of the gut is one of the most extensive networks of immune cells in the body and the community of gut commensals within the gut lumen has a profound impact on its phenotype. Through direct contact with mucosa or soluble chemical mediators, several commensal species of Lactobacillus and Bifidobacterium have been found to regulate host immunity. However, the role of gut microorganisms in host immune responses is not straightforward. For instance, segmented filamentous bacteria colonizing the ileum influence protective immune responses, which can trigger autoimmunity in susceptible hosts.
In the current fight against the COVID-19, anti-viral host defense mechanisms may determine disease severity and evolution
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is generally mild, it sometimes progresses into severe pneumonia and causes death. This occurs especially in the elderly and individuals with co-morbidities, as host immune cells release more inflammatory cytokines than necessary (called a “cytokine storm”), which can cause widespread inflammation and a fatal outcome.
This overreactive immune system seems to indicate that immunosuppressive treatments that block cytokine production might help calm the “cytokine storm” and aid recovery in patients. In addition, preliminary data show that, as disease severity progresses in patients with COVID-19, a parallel rise in inflammatory cytokine levels may drive the reduction and functional exhaustion of CD8+ T cells, which could open a new target potential in fighting COVID-19.
In support of these findings, recent studies (here; here) have revealed reduced levels of circulating CD8+ T cells in people infected with SARS-CoV-2, especially in severe cases. This has led scientists to argue that the circulating CD8+ T cells levels could be an independent predictor for COVID-19 severity and treatment efficacy.
In this context, one might argue that gut microbiome-immune system crosstalk could work as a team to normalize host immune responses, though further basic and clinical research is needed to better understand how SARS-CoV-2 affects the immune system.
How might the gut microbiome fare when fighting COVID-19?
While patients infected with SARS-CoV-2 typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms (even early on in the course of the disease) such as diarrhea, vomiting and abdominal pain.
These symptoms may have their roots not only in the use of antibiotics for managing bacterial pneumonia secondary to the viral respiratory infection, but also in the virus’ capacity to infect and replicate in the gut, given that viral RNA has been recovered from the stools of infected patients. Moreover, the receptor that SARS-CoV-2 uses for infecting host cells can be expressed in the oral cavity, esophagus, stomach, intestine (and in gut-distal organs including the gall bladder, heart muscle, kidney and even the cerebellum).
The involvement of the gastrointestinal milieu in COVID-19 is also supported by small case series showing that some patients have an altered gut microbiota composition, with depleted Lactobacillus and Bifidobacterium. Undoubtedly, we will see larger cohort studies being published in the future.
Although the gut-lung axis is not new and has been proposed in the development of certain respiratory conditions, the respiratory symptoms of COVID-19, the gastrointestinal tropism of SARS-CoV-2, and an altered gut microbiota in some cases make considering the gastrointestinal tract as a potential target in the disease’s management and transmission worthwhile.
Could probiotics and prebiotics play a major role in defending against SARS-CoV-2?
Although at first sight, the role of gut bacteria in improving respiratory outcomes might seem like science fiction, previous research in mice and humans has highlighted the benefits of food fibers and probiotics in ameliorating some symptoms and health outcomes in respiratory diseases.
More relevant to the current COVID-19 pandemic, two meta-analyses (here; here) reported the efficacy of probiotics in reducing the incidence and duration of viral respiratory infections. Recently, China’s National Health Commission and National Administration of Traditional Chinese Medicine recommended probiotics in the treatment of patients with severe COVID-19 infection as a means of preventing secondary bacterial infection.
However, in the light of these preliminary findings, it is too early to recommend probiotics for preventing pneumonia or reducing intensive care unit mortality in patients with COVID-19, concluded correspondence in The Lancet Gastroenterology & Hepatology.
When it comes to prebiotics, a previous study has revealed that a diet supplemented with the fermentable fiber inulin for 8 weeks led to increased levels of CD8+ T cells in the lungs of mice infected with the influenza A virus. Mice supplemented with inulin showed a 10-fold reduction in the influenza A viral load and increased survival. To what extent increasing soluble fiber-rich foods as means for improving recovery and survival in people infected with SARS-CoV-2 remains to be seen.
Even though the potential of fecal microbiota transplants in the transmission of COVID-19 is not known, an international expert panel recommends screening all FMT donors for SARS-CoV-2 and quarantining frozen samples for 30 days and releasing them only if the donor has not developed symptoms.
On the whole, available data until now has revealed that the SARS-CoV-2 infection goes beyond the lungs and may affect not only the immune system but also the gastrointestinal tract. Although more evidence in humans is needed before recommending probiotics and prebiotics in patients with COVID-19, considering the gastrointestinal tract and gut microbiome in managing the virus could offer a valuable approach in the clinical setting.
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