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 patient’s rectal microbiome. An advanced microbiome diagnosis, however, could improve non-surgical treatment of uncomplicated AA.

Methadone maintenance treatment is more effective than compulsory detoxification in addressing gut microbiota dysbiosis caused by heroin abuse

“…Second, we only included male patients due to the scarcity of female HUD patients. Third, the analyses in this study predominantly concluded at the genus level due to the limitations of 16S rDNA sequencing in accurately resolving taxa beyond this level (Johnson et al, 2019;Blohs et al, 2023). However, we still propose a strong correlation between HUD and gut dysbiosis.…”

Germinal center BCR maturation in appendicitis reveals a role for antigen-specific adaptive immune responses during disease

“…Within the significant genera, we found opportunistic pathogens such as Parvimonas and Peptostreptococcus were significantly increased in appendicitis ( Figure 5D ). A previous publication also reported increased Parvimonas specific to complicated appendicitis that was associated with oral bacterial pathogens such as Fusobacterium 10 . While increased Fusobacterium has repeatedly been associated with appendicitis in the literature, we observed a trend towards an increase in this genus, although it did not reach significance 7, 22, 23 .…”

“…From these studies a few common findings have emerged, including a relative decrease in Bacteroides and increases in oral pathobionts such as Fusobacterium, Gemella and Porphyromonas in appendicitis samples [6][7][8] . The degree of dysbiosis appears to correlate with disease severity, with oral taxa and opportunistic pathogens such as Parvimonas micra more often enriched in complicated appendicitis characterized by gangrenous or perforated tissue, while uncomplicated cases had a lesser dysbiosis composed of typical gut commensal taxa [9][10][11] . Further implicating the microbiome in disease etiology is the result of the APPAC randomized clinical trial, which demonstrated that antibiotic therapy alone can be effective in some cases of appendicitis 12 .…”