Gut bacteria point to novel strategies for combating asthma, COVID-19

Lungs
Australian researchers found a protective effect of L-tyrosine and p-cresol sulfate in mouse asthma models as well as preclinical models of lung inflammation caused by COVID-19. (Pixabay)

One of the questions researchers have about the microbiome—the population of bacteria that live in the gut—is how it might be influenced by the immune system. A team of researchers from Monash University's Central Clinical School in Melbourne, Australia, set out to answer that question, and in the process found two molecules the scientists believe could offer new treatment strategies for asthma.

One of the molecules, L-tyrosine, is sold over the counter as a dietary supplement. So, the researchers plan to fast-track it into clinical trials. If it works, they believe it might also be used to treat acute respiratory distress syndrome (ARDS) in COVID-19 patients, they reported in the journal Nature Immunology.

The researchers started by transplanting gut bacteria from an immune-deficient mouse model into normal mice and observing the animals’ immune systems. They were surprised to discover that the gut bacteria exhibited enhanced metabolism of L-tyrosine, resulting in the production of a byproduct called p-cresol sulfate (PCS).

They went on to give either L-tyrosine or PCS to mice and discovered that the supplements protected the animals from lung inflammation. “PCS travels all the way from the gut, to the lungs, and acts on epithelial cells lining the airways to prevent the allergic asthma response,” said lead author and Monash professor Benjamin Marsland, Ph.D., in a statement.

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In addition to testing L-tyrosine and PCS in mouse asthma models, the Australian team tried them in animal models of ARDS, a lung disorder that’s common in severe cases of COVID-19. They observed a protective effect there, too, they reported.

Several research teams are pursuing novel immune targets in lung disease. A Mayo Clinic team, for example, reported in November that they discovered a link between the proliferation of tissue-resident memory CD8+ T cells and persistent lung inflammation—a finding they believe could point to new treatments for viral pneumonia, including that caused by COVID-19.

As for the microbiome, it has inspired research across a range of diseases including cancer, inflammatory bowel disease and obesity. Last year, researchers from the universities of Edinburgh and Dundee reported that the over-the-counter probiotic Bacillus subtilis had a protective effect in preclinical models of Parkinson’s disease.

The next step for the Monash University team is to plan a clinical trial of L-tyrosine in asthma patients. PCS has known toxicities in people, so the researchers are developing a form of the molecule that will protect against lung inflammation without causing side effects. They believe the drug will be able to be delivered directly to the lungs in an inhaled formulation, they said.