P0177 Dietary prevention of undernutrition reduces intestinal inflammation in a DSS-induced model of colitis and is associated with anti-inflammatory metabolites-producing bacteria

Abstract Background Patients with inflammatory bowel diseases (IBD) have a high-risk for undernutrition1. Undernutrition is associated with higher complications such as an increased mortality rate, a higher disease activity and an impaired quality of life in IBD patients. The aim of the present study was to assess whether dietary prevention of undernutrition may alleviate intestinal inflammation in mice with colitis. Methods Mice were fed with an enriched diet (ED; 4.7 kcal/g, 38% kcal from milk fat, 29% kcal from sucrose) or a standard diet (SD; 3.9 kcal/g, 8% kcal from milk fat) for 31 days. Colitis was chemically induced by 1% dextran sulfate sodium (DSS) in male C57BL/6 mice for 7 days. Colitis severity was assessed by monitoring inflammation-related biomarkers, as colon weight/length ratio and fecal calprotectin. Gut microbiota composition was determined by 16S rRNA gene sequencing performed on DNA extracted from cecal contents. Body weight and body composition were recorded. Results In SD-fed mice, DSS induced body weight loss (p<0.01) associated to a decrease of fat and lean mass (p<0.01). In mice with DSS-induced colitis, ED for 3 weeks prevented body weight loss (p<0.001) and body composition alteration. ED prevented DSS-induced higher colon weight/length ratio and fecal calprotectin. Compared to SD, ED significantly increased relative abundance of 8 bacterial species, including Eisenbergiella tayi (log2FC=3.8474, p_adj<0.01) and Lactococcus lactis (log2FC=1.6034, p_adj<0.05) (Figure 1A), which are producing anti-inflammatory metabolites such as butyrate, lactate or succinate. Relative abundances of Pseudoflavonifractor capillosus and Vescimonas coprocola were negatively correlated with inflammatory markers, such as fecal calprotectin levels (r=-0.7347, p:adj=0.0332; r=-0.7846, p=0.0265, respectively) (Figure 1B). Conclusion Prevention of undernutrition by ED reduces DSS-induced colitis severity and is associated with higher anti-inflammatory metabolites-producing bacteria. Further studies are now required to understand the underlying mechanisms involved in these ED-induced effects. References 1. Bischoff, S. C. et al. ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clin Nutr 42, 352–379 (2023).