Although the idea of a gut-lung connection is not new, the COVID-19 pandemic has aroused scientists’ interest in finding out more

While COVID-19 is mainly a respiratory illness, recent findings suggest that the SARS-CoV-2 virus also affects the gut microbiota and can lead to inappropriate immune responses that prevent the elimination of the virus. The fact that long-term complications and persistent symptoms after recovery have been linked to alterations in gut microbiota composition supports a connection between what happens in the gastrointestinal tract—the largest immunological organ in the body—and lung health.

While the idea of a gut-lung connection is not new, it has not commanded as much attention among researchers as the gut-brain axis. Nevertheless, the current COVID-19 pandemic has put it in the spotlight. From early life, all mucosal linings in the human body are connected and are where pathogens and other insults meet immune cells. The tonsils, the lungs and the Peyer patches within the small intestine are examples of interconnected compartments.

Hence, it is not surprising that a gut microbiota in good shape is important for ensuring proper immune responses in the lungs to keep respiratory tract infections at bay. For example, altering the gut microbiota with antibiotics increases the severity of viral respiratory infections such as influenza (flu).

 

How does the gut microbiota affect respiratory outcomes?

A gut microbiota in good shape is important for ensuring proper immune responses in the lungs to keep respiratory tract infections at bay

The gut microbiota and the lungs are connected in two directions. Simply put, immune cells located in the gut wall can leave the gut and travel through the lymphatic system to other locations around the body including the lungs and, inversely, respiratory infections can alter gut microbiota composition and functions.

Jordi Espadaler-Mazo, PhD, a molecular biologist with a strong scientific interest in probiotics and personalized medicine, explained to GMFH editors via email two examples that support the close connection between gut and lungs. First, infant gut microbiota development has been shown to predict asthma risk later in life and, secondly, individuals with chronic obstructive pulmonary disease are 2 to 3 times more likely to be diagnosed with inflammatory bowel disease.

While the respiratory tract was traditionally considered sterile, we now know that it has its own microbiota that is linked to the gut microbiota. As such, improving your gut microbiota through diet provides an opportunity to look after your lungs.

One dietary element is the fermentable fiber inulin, which has been shown to prevent flu in mice by involving both innate (inflammatory responses) and specific immune responses.

Several human clinical trials have studied the effect of probiotics on upper respiratory tract infections such as the common cold. There are also studies showing that certain probiotic strains can reduce atopic diseases in infants and fight off the release of inflammatory compounds by immune cells in smokers. Furthermore, in healthy children and adults, specific Lactobacillus and Bifidobacterium probiotic strains have shown benefits in reducing the duration of respiratory and gastrointestinal symptoms and thus absenteeism at school and work.

Espadaler-Mazo acknowledges, however, that there are limitations on studies that assess the effect of probiotic interventions on upper respiratory tract infections that limit generalizing the findings. Those limitations include the huge disparity in outcomes between studies, overreliance on patient-reported diagnoses and symptoms and forgetting that the benefits of probiotics for the immune system are specific at the strain level.

 

What do we know so far about the role of diet and probiotics in reducing symptom duration and viral load in patients with COVID-19?

Given the emerging involvement of the body’s immune and digestive systems in the development of COVID-19, scientists have turned to science-based ways of changing the gut microbiota to reduce the risk of complications due to COVID-19.

Professor Philip Calder, Professor of Nutritional Immunology at the University of Southampton, acknowledges that strategies that optimize the gut microbiota and that will, in turn, support immune response are likely to have an impact on respiratory health.

While nothing people can eat will stop them from getting infected with COVID-19, a healthy, diverse and well-balanced diet will provide the nutrients required by the immune system to function well and promote a balanced gut microbiota. According to Professor Calder, it seems likely that a Mediterranean-like diet, which is well understood to help control inflammation and provides the nutrients needed to support the immune system, is also important for respiratory health.

Some studies also suggest that there may be a role for manipulating the gut microbiota when treating those with SARS-CoV-2 infection or COVID-19.

According to Professor Calder, it seems likely that a Mediterranean-like diet is also important for respiratory health

That is the case of a recent clinical trial that showed that a specific mixture of probiotic strains Lactiplantibacillus plantarum KABP022, KABP023 and KAPB033 plus Pediococcus acidilactici KABP021 at doses of 2 x 109 colony-forming units for 30 days may help reduce symptom duration and viral load in 300 symptomatic patients with a positive diagnosis for COVID-19. The benefits were independent of the participants’ gut microbiota composition at the beginning of the study and seem to be explained by probiotic-related benefits for the immune system.

As stated by Espadaler-Mazo, who is the study’s corresponding author: “We sought to provide sound evidence of the utility of this probiotic formulation to improve both objective (viral load, pulmonary infiltration quantified on digital X-ray scans and SARS-CoV2-specific antibodies in serum) and patient-reported symptoms in COVID-19, trying to overcome limitations found in past studies”.

 

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Enaud R, Prevel R, Ciarlo E, et al. The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalks. Front Cell Infect Microbiol. 2020; 10:9. doi: 10.3389/fcimb.2020.00009.

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