Obesity-associated microbiome effects can be mitigated by weight loss and/or sulindac in a murine model of colon cancer

Obesity is associated with an increased risk of colon cancer. We explored whether weight loss and/or treatment with the non-steroidal anti-inflammatory drug (NSAID) sulindac can alter fecal microbiotas associated with obesity in a mouse model of colon cancer. Azoxymethane-treated male FVB/N mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 15 weeks to promote diet induced obesity. The HFD mice were then randomized to remain on HFD (obese) or switch to LFD (formerly obese (FOb-LFD)). Half of each group was further randomized to receive sulindac treatment (140 ppm in the diet). All mice were euthanized seven weeks later. Sulindac did not affect body weight. Obese mice had greater tumor multiplicity and burden than all other groups (P<0.05). The fecal microbes Prevotella and Akkermansia muciniphila correlated with tumor multiplicity and reduced by sulindac in obese mice as determined by 16S rDNA sequencing. Our findings suggest that an investigation regarding the effects of NSAID treatment on colon cancer risk and/or progression in obese patients is warranted.