Acute appendicitis manifests as two microbiome state types with oral pathogens influencing severity

Abstract

Mounting evidence suggests that acute appendicitis (AA) is not one but two diseases: complicated appendicitis, which is associated with necrosis leading to perforation or periappendicular abscess, and uncomplicated appendicitis, which does not necessarily result in perforation. Even though AA is the most frequent cause of surgery from abdominal pain, little is known about the origins and etiopathogenesis of this disease, much less regarding the different disease types. In this study, we investigated the microbiome of samples from the appendix, rectum and peritoneum of 60 children and adolescents with AA to assess the composition and potential function of bacteria, archaea and fungi. The analysis of the appendix microbial community revealed a shift depending on the severity of the AA. This shift was reflected by two major community state types that represented the complicated and uncomplicated cases. We could demonstrate that complicated, but not uncomplicated, appendicitis is associated with a significant local expansion of oral, bacterial pathogens in the appendix, most strongly influenced by necrotizing Fusobacterium spp., Porphyromonas and Parvimonas. Uncomplicated appendicitis, however, was characterised by gut-associated microbiomes. Our findings support the hypothesis that two disease types exist in AA, which cannot be distinguished beyond doubt using standard clinical characterization methods or by analysis of the patients rectal microbiome. An advanced microbiome diagnosis, however, could improve non-surgical treatment of uncomplicated AA. ImportanceWith a lifetime risk of up to 17%, acute appendicitis is one of the most frequent causes of emergency abdominal surgery in westernized countries. Latest literature reports suggests that appendicitis manifests in two disease types: complicated and uncomplicated appendicitis with different, yet unknown, etiopathogenesis. In this study, we investigated the microbial composition (bacteria, archaea and fungi) from 60 children and adolescents that were diagnosed with acute appendicitis. Appendix, rectal and peritoneal samples were analysed using amplicon and metagenomic sequencing. Our results suggest that acute appendicitis manifests in three microbial state types that reflect complicated and uncomplicated appendicitis as well as special cases that are caused by bacterial overgrowth. Strikingly, uncomplicated appendicitis appears to be caused by gut-associated pathogens while complicated appendicitis is driven by oral-associated microbes such as Fusobacterium sp. or Porphyromonas sp. The findings provided in our study are of special interest to understand the etiopathogenesis of both complicated and uncomplicated appendicitis.