Long-Term Overconsumption of Fat and Sugar Causes a Partially Reversible Pre-inflammatory Bowel Disease State

Abstract

Nutrition appears to be an important environmental factor involved in the onset of inflammatory bowel diseases (IBD) through yet poorly understood biological mechanisms. Most studies focused on fat content in high caloric diets, while refined sugars represent up to 40% of caloric intake within industrialized countries and contribute to the growing epidemics of inflammatory diseases. Herein we aim to better understand the impact of a high-fat-high-sucrose diet on intestinal homeostasis in healthy conditions and the subsequent colitis risk. We investigated the early events and the potential reversibility of high caloric diet-induced damage in mice before experimental colitis. C57BL/6 mice were fed with a high-fat or high-fat high-sucrose or control diet before experimental colitis. In healthy mice, a high-fat high-sucrose diet induces a pre-IBD state characterized by gut microbiota dysbiosis with a total depletion of bacteria belonging to Barnesiella that is associated with subclinical endoscopic lesions. An overall down-regulation of the colonic transcriptome converged with broadly decreased immune cell populations in the mesenteric lymph nodes leading to the inability to respond to tissue injury. Such in-vivo effects on microbiome and transcriptome were partially restored when returning to normal chow. Long-term consumption of diet enriched in sucrose and fat predisposes mice to colitis. This enhanced risk is preceded by gut microbiota dysbiosis and transcriptional reprogramming of colonic genes related to IBD. Importantly, diet-induced transcriptome and microbiome disturbances are partially reversible after switching back to normal chow with persistent sequelae that may contribute to IBD predisposition in the general population.

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

“…21 Subsequent studies indicated that a Western style diet impairs epithelial barrier function in mice and susceptibility to chemically induced (toxic) colitis. [22][23][24] In line with this concept, a glucose-enriched diet deteriorated colitis in IL10 −/− mice and toxic colitis, 25 which was similarly noted for fructose and sucrose enrichment. [26][27][28][29] Not only macronutrients, but also food additives typically enriched in a Western diet (and a related lifestyle) promote susceptibility to colitis.…”

“…Saturated and polyunsaturated fatty acids Experimentally promoting gut inflammation, 36 38 arguably restriction in nutritional trials [39][40][41] Restrict animal fat (regardless of source), deep fried and ultra-processed food Sucrose, Glucose, Fructose Experimentally promoting gut inflammation, [23][24][25][26][27] arguably restriction in nutritional trials [39][40][41] Restrict soft drinks, sweets, ready-made food…”

Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

“…Animal models utilizing high-fat diets (plus glucose) to induce obesity, metabolic endotoxemia, and insulin resistances show alterations in the gut microbiota [ 28 , 35 ]. In addition, these models have been instrumental in showing that high-fat diets also cause an increase in intestinal permeability and inflammation [ 30 , 59 , 122 , 123 , 124 ]. In human subjects, intestinal inflammation has been observed in more advanced liver diseases such as cirrhosis and HCC [ 125 , 126 ].…”

Individuals with Metabolic Syndrome show altered fecal lipidomic profiles with no signs of intestinal inflammation or increased intestinal permeability: a pilot study

“…Animal models utilizing high-fat diets (plus glucose) to induce obesity, metabolic endotoxemia, and insulin resistances show alterations in the gut microbiota (18,21). In addition, these models have been instrumental in showing high-fat diets also cause an increase in intestinal permeability and inflammation (45,(112)(113)(114)(115). In human subjects, intestinal inflammation has been observed in more advanced liver diseases like cirrhosis and HCC (116,117).…”