Abstract Background Colon anastomosis leak is the most feared complication in colorectal surgery, with high morbidity and mortality. Despite the identification of correctible risk factors, its incidence has remained stable for the past 50 years. One of the risk factors is obesity, a systemic disease whose prevalence is continuously increasing worldwide. To understand the implicated mechanisms, and to develop therapeutic strategies, characterization of colon anastomosis healing in obese subjects is mandatory. Aims We aimed to describe the colon anastomotic healing process in obese mice, with a secondary aim to identify potential targets to decrease post-operative leaks. Methods Three groups of mice were fed different diets for 16 weeks: normal diet only (ND), high-fat diet reverted to normal diet on day of surgery (HF-ND), or high-fat diet only (HF-HF). Surgery consisted of left colon hemi-transection on the anti-mesenteric wall, and subsequent anastomosis with separate stitches. N=5 mice from each group were sacrificed at days 3, 5, 7, 10 and 14 after surgery. Results HF-HF mice had diarrhea and lost weight up to day 10 after surgery, compared to day 1 for ND mice. Overall, abscess rate was 4% in ND and HF-ND, and 8% in HF-HF mice. Free leak rate was 0% in ND and HF-ND, and 16% in HF-HF mice (p=0.03). Angiogenesis was decreased in HF-HF mice at day 5 compared to ND mice (p=0.02). Conclusion Obese mice undergoing continued high-fat diet (HF-HF) globally demonstrated worst outcomes after colon anastomosis with increased leak rates, and decreased angiogenesis. Despite having similarly low angiogenesis, these results seem to be mitigated in high-fat diet fed mice reverting to normal diet on day of surgery (HF-ND), hinting towards an involvement of gut microbiota. Further analysis of gut microbiota and angiogenesis pathways are warranted in order to determine therapeutic strategies.
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