It may sound surprising, but substances produced by bacteria living in our intestines could soon become powerful new treatments for chronic lung inflammation. This is the conclusion reached by a research team led by Professor Tomasz Wypych from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw. Their findings were recently published in the prestigious Nature family journal Signal Transduction and Targeted Therapy.

The bacteria inhabiting our gut, collectively known as the microbiome, are far from random intestinal occupants. Over millions of years of coevolution, humans and these microscopic organisms have formed a complex biological partnership. While scientists have been studying this relationship for some time, only now are its medical implications becoming truly clear.

“For about 20 years, research has shown that the microbiome influences virtually all physiological processes in mammals, including the immune system,” says Professor Wypych.

His team focuses on the so-called gut-brain and gut-lung communication axes. One of the main “messengers” between these organs are metabolites – small molecules produced when gut bacteria break down various compounds. These metabolites travel through the bloodstream and reach the brain, lungs, and other tissues throughout the body.

The latest study centers on bile acids. Humans produce only two primary bile acids, which play a crucial role in fat digestion. For gut bacteria, however, bile acids are toxic. As a result, microbes have evolved ways to chemically modify them.

“During evolution, some bacteria developed mechanisms to neutralize bile acids for their own benefit but, at the same time, yield compounds that benefit the host. This gave them an evolutionary advantage over other microbes,” explains Professor Wypych.

This process is capable of generating thousands of chemically diverse molecules. According to the researchers, microbiome-modified bile acids represent a rich and largely untapped source of potential new drugs.

Among these compounds, the team identified one particularly promising molecule: isolithocholic acid. It proved highly effective at suppressing excessive immune responses in the lungs during inflammatory and pathological conditions such as acute respiratory distress syndrome, severe infections, and asthma.

The compound acts on lung macrophages – immune cells that reside in the respiratory tract and serve as the body’s frontline defenders. They engulf and neutralize bacteria, viruses, dust particles, and airborne allergens. Under the influence of isolithocholic acid, these cells produce fewer chemokines – signaling molecules that normally recruit large numbers of immune cells to sites of inflammation.

“Fewer chemokines mean fewer incoming immune cells, such as eosinophils in asthma,” says Professor Wypych. “These cells release toxic substances meant to eliminate threats, but they also damage healthy lung tissue. This is why chronic inflammatory diseases often lead to tissue destruction and impaired lung function.”

Animal studies confirmed that reducing this excessive immune influx significantly benefits lung health.

“Our findings represent an early step toward developing a new drug that could help treat chronic inflammatory lung diseases,” the researcher says.

At the same time, the team is working on specialized probiotic supplements containing selected bacterial strains that protect against asthma.

In their previous work, prof. Wypych and his colleagues identified two other medically interesting gut-derived metabolites: p-cresol sulfate, produced during the breakdown of the amino acid tyrosine, and indole-3-propionic acid, which originates from tryptophan metabolism.

Interestingly, experiments using a mouse model of asthma revealed that indole-3-propionic acid is key to the development of immune tolerance to house dust mite allergens early in life. Because epidemiological studies in humans reveal a strong link between antibiotic treatment – which disrupts the gut microbiome and lowers levels of this protective metabolite – and an increased risk of developing asthma, researchers now see a promising opportunity for prevention. By restoring the compound through dietary supplementation (e.g. in milk) during antibiotic therapy in babies, they hope to reduce the likelihood of developing asthma and allergies later in life.

One thing is becoming increasingly clear: our gut microbiome is far more than a digestive aid. It may soon become a key ally in the fight against chronic respiratory disease.