Nutritional and dietary drivers in the pathogenesis of acute appendicitis: the nutrition-microbiome-genetic axis

Acute appendicitis is one of the leading causes of surgical emergency hospitalizations. However, the mechanisms leading to the development of appendicitis are poorly understood. Current knowledge suggests an interplay probably led by dietary habits with impact on the microbiome which elicits responses in genetically predisposed individuals. The aim of this review is to assess the nutrition-microbiome-genetic axis associated with acute appendicitis development. The main dietary and nutritional patterns associated to acute appendicitis were low consumption of fibre, water and fish oil, and high levels of saturated fat, salt, processed meat and ultra-processed foods. Collectively, these westernized dietary patterns (WDP) may increase more than 40% the risk of developing acute appendicitis. The WDP are associated to shifts in the microbiome observed in inflamed appendices such as an increased abundance of Fusobacteria together with a lower level of Proteobacteria. While dietary patterns and associated changes in the microbiome may affect a large proportion of the population, only a relatively small percentage develop acute appendicitis suggesting the existence of predisposing genetic factors. Several single nucleotide polymorphisms (SNP) have been identified linking nutrition and microbiome to the genetic background in acute appendicitis. These include the HLA-C SNP rs2524046, associated with coeliac disease, and the variant rs9953918 of NEDD4L (involved in fluid/water mobilization). A hypothetical allergy model for appendicitis has been recently proposed providing a preliminary groundwork that identifies SNPs in or near IL-6, IL-10 and IL-13, NOD2, CCL22 and CTLA4 involved in the pathogenesis of both inflammatory diseases.