Berberine May Reduce Inflammation of Lung Tissues in Patients With Metastatic Colorectal Cancer

Berberine changed the richness, evenness, and biodiversity of the lung microbiota in patients with colorectal cancer (CRC), according to findings from recent study published in Heliyon. Berberine may selectively regulate the abundance of certain species in the lung microbiota, improving alpha diversity and reducing inflammation caused by microbiota imbalance.

“As chronic inflammation is now recognized as an important carcinogen, the role of bacteria in the occurrence and development of lung cancer has attracted great attention from researchers worldwide,” wrote study authors.

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CRC remains a significant cause of mortality around the world. Evidence suggests that imbalances in the gut microbiome and intestinal microbiota can lead to CRC because of inflammation and immune dysregulation; however, there is little research on the lung microbiome (although studies suggest that the lung and gut microbiotas are connected). Further, it’s important to consider the lungs in CRC because the disease often metastasizes in the liver and lungs.

Berberine is a soquinoline quaternary alkaloid that may regulate the intestinal microbiota in CRC and have other anticancer properties. There are few studies that evaluate berberine for the lung microbiota and related mechanisms in CRC, and so investigators of the current study evaluated it in a using a nude mouse xenograft model and colon cancer cell-derived conditioned medium (CM).

Investigators evaluated these outcomes by comparing berberine with probiotics or a combination of berberine and probiotics. The berberine alone was shown to increase the abundance of Bacteroidetes, Bacteroidia, Bacteroidales, Lactobacillaceae, Lactobacillus, and Acinetobacterspecies in the mice with colon cancer, who had already had a less rich lung microbiota compared to the control group. It also reduced the abundance of strains such as Actinobacteria, Bacillales, Staphylococcaceae and Staphylococcus.

The combination of berberine and probiotics increased the abundances of Gammaproteobacteria, Lactobacillaceae, Lactobacillus, and Acinetobacter as well, which suggests that probiotics also be needed to regulate certain bacterial species and improve microbial diversity.

The mice with CRC generally had less lung microbiota that acted in the processes of lysosomes, flavanol biosynthesis, glycosaminoglycan degradation, and glycosphingolipid biosynthesis; however, berberine significantly increased these species numbers. Berberine also increased the abundance of bacteria that participated in sporulation, although probiotics or berberine-probiotics were more effective at increasing this flora.

Berberine can also reduce inflammation in the lung tissue via improving intestinal microbiota or regulating cells in the lung tissue environment. On its own, berberine modestly reduced IL-6 and IL-10 compared to the control. However, when combined with a probiotic, its anti-inflammatory effects were significantly improved, as seen by the significant decrease of inflammatory marker IL-17.

Finally, the alkaloid prevented the malignant transformation of lung epithelial cells and regulated the expression of genes that are involved in cell damage repair. During the study, investigators also observed that berberine regulated extracellular matrix remodeling.

REFERENCE

Yang W, Yang T, Huang B, Chen Z, Liu H, Huang C. Berberine improved the microbiota in lung tissue of colon cancer and reversed the bronchial epithelial cell changes caused by cancer cells. Heliyon. 2024. doi:10.1016/j.heliyon.2024.e24405.