Gut Bacteria Offer Insight into Molecules Protective Against Asthma and COVID-19

A study from researchers at Monash University in Melbourne has identified two molecules in the gut microbiome that can protect against asthma and may possibly reduce the severity of an asthma attack.

The study, published in Nature Immunology, found that L-tyrosine, an amino acid commonly sold as a dietary supplement, and gut bacteria byproduct p-cresol sulfate (PCS) have been previously shown to affect asthma outcomes. Additionally, some animal models have suggested they may play a role in treating respiratory illness in severe cases of COVID-19.

In the study, Professor Benjamin Marsland and colleagues sought to understand how the immune system affects the gut microbiome using a mouse model with a limited immune system. The investigators transferred the gut bacteria from this mouse model in mice with a normal functioning immune system to identify which bacteria exerted effects on the overall healthy immune system.

The generation of PCS resulted in significant protective effects against allergic airway inflammation, a surprising finding according to the researchers. The PCS in the model was produced via enhanced bacterial metabolism of the amino acid L-tyrosine. In a statement about the researchers, Professor Marsland noted that the metabolite identified in the study “may have a role in other inflammatory diseases,” included COVID-19.

Running with this rationale, the investigators tested the metabolites in animals with acute respiratory distress syndrome (ARDS), a risky complication of COVID-19. Similar to the asthma findings, L-tyrosine and PCS was protective against ARDS.

The investigators added in their study that they have found the inhalation of PCS directly protects against lung inflammation, indicating that the metabolite may hold potential as an inhaled preventative therapy.

Given the safe nature of L-tyrosine and the widespread use of the amino acid in dietary supplements, it’s likely this therapy could be fast-tracked into clinical trials for asthma and COVID-19. "It's very important that a thorough clinical study is performed in order to determine whether L-tyrosine is effective in people with asthma,” said Professor Marsland, “and for us to determine what is the correct dose and treatment regime."

In contrast, PCS is suspected to be toxic as it is often unable to clear in many patients with chronic kidney disease. Professor Marsland and colleagues from Monash University have said they have started developing a PCS form that doesn’t feature its potential side effects but may be used as a protective against asthma. The study investigators commented that they will test either PCS or L-tyrosine in a 2021 clinical trial in patients with asthma.

The gut microbiome includes the population of bacteria, include probiotic bacteria, that reside in the gut. Research has consistently shown an association with gut bacteria and immune health, with some investigators also showing a connection between the microbiome and cancer, obesity and inflammatory bowel disease. Some studies have even gone as far to suggest that the microbiome influences neurological health, with a preclinical study from the Edinburgh and Dundee reporting last year that a probiotic strain may protect against Parkinson’s disease.

As reported in the summer of 2020, the global market for human microbiome products and research is on an exponential growth trajectory. Clinical trials focused on the microbiome have increased to assist in market development, but lack of uncertainty relating to the performance of microbiome-related drugs may impede growth in this field.