Acute appendicitis manifests in two microbiome state types, with oral pathogens driving severity

Mounting evidence suggests that acute appendicitis (AA) is not one but two diseases, with complicated appendectomy that reaches perforation eventually if untreated and uncomplicated appendectomy which does not. 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. Here, we investigated the microbiome of appendix, stool and peritoneum samples from 60 children and adolescents with AA to assess the composition and potential function of bacteria, archaea and fungi. The microbial community of the appendix revealed a severity-specific shift. This shift was reflected by two major community state types that represented complicated and uncomplicated cases. We demonstrated that complicated, but not uncomplicated, appendicitis is associated with a significant local expansion of oral bacterial pathogens in the appendix, driven by necrotizing Fusobacterium spp., Porphyromonas and Parvimonas. On the contrary, uncomplicated appendicitis was characterized by gut-associated microbiomes. Our findings support the notion of two disease types in AA, which can currently not be distinguished using standard clinical characterizations, nor the analysis of the patient's stool microbiome. An improved diagnostics could, however, improve non-surgical treatment of uncomplicated AA.