The Combined Effect of Western Diet Consumption and Diclofenac Administration Alters the Gut Microbiota and Promotes Anastomotic Leakage in the Distal Colon

Background: Obesity, Western diet (WD) consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are co-occurring and modifiable factors associated with microbiome dysbiosis and anastomotic leakage. We studied the combined effect of a Western-type diet (WD) and diclofenac, a standard NSAID used in surgical patients, on anastomotic healing and gut microbiota composition following distal colon resection. Methods: Forty-two rats were fed a WD for 6 weeks, after which they were randomized to either parenteral diclofenac 3 mg/kg/day or saline started on the day of surgery and continued for three days. The surgical procedure involved distal colon resection with anastomosis. Animals were sacrificed on postoperative day (POD)-3 or POD-5. Anastomotic healing was assessed and correlated with diclofenac treatment and gut microbiota composition, analyzed by 16S rRNA marker gene amplicon sequencing. Mucosal integrity of the anastomosis was evaluated by histological analysis. Results: Anastomotic leakage rate was 100 percent (8/8) in diclofenac-treated rats and 10 percent (1/10) in saline-treated controls on POD-5. Diclofenac administration in WD-fed animals induced a shift in microbiota composition, characterized by an increase in microbiota diversity on POD-5 and a significant 15-fold, 4-fold, and 16-fold increase of Proteobacteria, Bacteroidetes, and Verrucomicrobia, respectively. Diclofenac use in WD-fed animals caused mucosal erosion on POD-5, a phenomenon not observed in control animals. Conclusions: Consumption of a Western diet combined with diclofenac administration shifts the microbiota composition, associated with clinically relevant AL in the distal colon of rats.