Chemopreventive activity of celecoxib can be explained in part by its effects on the intestinal microbiota and its metabolites in mice

Recent research has shown that the effects of pharmacological treatments need to be disentangled from the effects of specific diseases on the human microbiota, as drug therapy effects may be a potential confound in human microbiome studies. However, to what extent drug treatment effectiveness is related to changes in gut microbiota composition and functionality is poorly studied.

A recent study, led by Prof. Andrew J. Dannenberg from the Department of Medicine at Weill Cornell Medical College at Cornell University in New York, has found that the chemopreventive activity of the drug celecoxib can be explained in part by its effects on the gut microbiota and its metabolites.

The researchers determined whether treatment with celecoxib, a nonsteroidal anti-inflammatory drug (NSAID) that is a selective cyclooxygenase (COX)-2 inhibitor used for relieving pain and inflammation, altered the luminal microbiota and its metabolites in association with reducing intestinal polyp burden in mice.

Celecoxib oral administration for 10 weeks markedly reduced intestinal polyp burden and size, while altering microbiota in both faeces and ileum in mice. Specifically, drug treatment decreased Lactobacillaceae and Bifidobacteriaceae and increased Coriobacteriaceae.

On the other hand, celecoxib treatment altered the faecal metabolomic profile by strongly reducing many faecal metabolites related to carcinogenesis, including glucose, amino acids, nucleotides, and lipids. These changes in metabolites may have contributed to reduced cell proliferation, as celecoxib treatment reduced proliferation in the base of normal-appearing ileal and colonic crypts.

To sum up, celecoxib alters the luminal microbiota and its metabolites along with reducing epithelial cell proliferation in mice, which may contribute in part to its chemopreventive activity. These results add new insights into the potential role of targeting the gut microbiota in decreasing cancer risk.

Reference:

Montrose DC, Zhou XK, McNally EM, et al. Celecoxib alters the intestinal microbiota and metabolome in association with reducing polyp burden. Cancer Prev Res (Phila). 2016; 9(9):721-31. doi: 10.1158/1940-6207.CAPR-16-0095.