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

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 (inter-domain amplicon and metagenome sequencing) 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 characterized 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 patient's rectal microbiome. An advanced microbiome diagnosis, however, could improve non-surgical treatment of uncomplicated AA.