A research team from Yonsei University College of Medicine has identified metabolic factors linked to low body mass index (BMI) that may exacerbate nontuberculous mycobacteria (NTM) lung disease.

NTM lung disease is caused by the infection of the lungs by NTM, bacteria that can thrive in diverse environments such as water, soil, and household items like showers, humidifiers, and saunas. This disease can lead to various infections, but lung infections are the most prevalent, accounting for over 90 percent of cases.

Among the 200 species of NTM, the mycobacterium avium complex (MAC) is a significant cause of chronic bacterial lung disease, with its incidence and prevalence rapidly increasing worldwide.

Clinical reports have frequently noted that MAC lung disease patients often have a low BMI, suggesting a potential link to disease progression. However, research on the underlying mechanisms has been limited.

As a result, the research team, led Professor Shin Sung-jae of the Department of Department of Microbiology, used a mouse model to investigate how low BMI affects the progression of MAC lung disease.

They induced a low BMI state in mice resistant to MAC lung disease by feeding them a low-protein diet and observing the disease progression.

The study revealed that the disease, which was stable in mice with a normal BMI, became progressive in those with a low BMI due to changes in lipid metabolism.

The low-protein diet led to increased expression of genes related to fatty acids and lipid metabolism in the lung tissue. This was consistent with the higher serum fatty acid levels found in patients with progressive MAC lung disease.

The mice on a low-protein diet showed increased expression of CD36, a protein involved in fatty acid absorption, and lipid accumulation in macrophages. The researchers confirmed that the uptake of fatty acids mediated by CD36 in macrophages contributed to bacterial growth.

When nutritional supplementation was provided to the mice on a low-protein diet, the disrupted lipid metabolism and elevated CD36 protein levels returned to normal, and the bacterial load decreased.

Also, the administration of an anti-CD36 antibody reduced fatty acid content in the lung tissue and lipid accumulation in macrophages, leading to a decrease in bacterial growth and stabilization of the disease.

"This study elucidates how metabolic lipid disturbances associated with low BMI contribute to the worsening of MAC lung disease,” Professor Shin said. “By recognizing MAC lung disease as a metabolic infectious disease, we can develop new treatment strategies targeting metabolic pathways to effectively manage nontuberculous mycobacterial lung disease."

The study results were published in eBioMedicine.