Acute Appendicitis in Children Is Associated With a Local Expansion of Fusobacteria

Background. Lumenal obstruction has typically been regarded as the cause of acute appendicitis (AA). Recent evidence including data from "antibiotics first" trials suggests that this disease may result from invasion of the appendix by specific pathogens. Small studies have identified an abundance of bacteria from the genus Fusobacterium in appendixes from patients with AA. We aimed to validate these findings in a larger cohort of children with appendicitis in addition to profiling the appendiceal microbiota in a population of children without appendicitis. Methods. Appendix swabs were collected from children undergoing appendectomy for AA (n = 60), incidental appendectomy for reasons other than appendicitis (n = 18), or ileocecectomy for inflammatory bowel disease (n = 7), in addition to samples from other sites. Bacterial 16S ribosomal RNA gene sequences from each sample were amplified, sequenced, and analyzed with the UPARSE and QIIME programs. Results. We found that the normal human appendix harbors populations of Fusobacteria that are generally absent in fecal samples from healthy adults and children. In patients with AA, Fusobacteria populations proliferate and often persist despite several weeks of broad-spectrum antibiotics prior to surgery. Relative to non-AA samples, AA samples were depleted of sequences from the genus Bacteroides. Phylogenetic analysis of sequence data indicates that F. nucleatum, F. necrophorum, and F. varium are the species of Fusobacterium observed in AA samples. Conclusions. These results indicate that the appendiceal niche harbors distinct microbial populations that likely contribute to the pathogenesis of appendicitis, which may one day be leveraged to improve the diagnosis and/or treatment of patients with AA.