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Letter
Local appendiceal dysbiosis: the missing link between the appendix and ulcerative colitis?
  1. X Roblin1,
  2. C Neut2,
  3. A Darfeuille-Michaud3,
  4. J F Colombel4,5
  1. 1Department of Hepato-Gastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France
  2. 2Laboratoire de Bacteriologie, Faculte de Pharmacie et INSERM U995, Universite Lile Nord de France, Lille, France
  3. 3Clermont Université, Université d'Auvergne, Jeune Equipe, Clermont-Ferrand, France
  4. 4Department of Hepatogastroenterology and INSERM U995, Universite Lille Nord de France, Lille, France
  5. 5Mount Sinai Medical School of Medicine, New York, New York, USA
  1. Correspondence to Dr X Roblin, Department of Hepato-Gastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France; xavier.roblin{at}chu-st-etienne.fr

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We read with great interest the article by Swidsinski et al reporting on a possible link between acute appendicitis and a local invasion by Fusobacteria. Investigating sections of 70 appendixes with confirmed appendicitis using rRNA-based fluorescence in situ hybridisation, the authors found bacteria deeply infiltrating the appendix. Fusobacteria (mainly Fusobacterium nucleatum/necrophorum) were specific components of epithelial and submucosal infiltrates in 62% of patients and were not found in various controls. The presence of Fusobacteria correlated positively with the severity of appendicitis. Conversely, main faecal microbiota including Faecalibacterium prausnitzii groups were significantly decreased with an inverse relationship with the severity of the disease.1

Altogether, these observations point to the presence of a local appendiceal dysbiosis with more bacteria with inflammatory properties and fewer bacteria with anti-inflammatory properties associated with acute appendicitis. The genus Fusobacterium is characterised by high proteolytic activity and comprises different distinct species. The most frequently encountered is F nucleatum, which is frequent in the oral sphere and implicated in periodontitis. F necrophorum has a high pathogenic potential and is implicated in life-threatening infections such as Lemierre's syndrome. In cattle, it is found in footrot disease and is also frequent in liver abscesses. The third important species is F varium. All species are part of the normal intestinal microflora. By contrast, F prausnitzii, which showed decreased numbers in appendicitis, is a bacterium with anti-inflammatory properties. Its numbers are also reduced in patients with inflammatory bowel disease and it is associated with postoperative recurrence of Crohn's disease.2

Over 30 studies have now analysed the association between appendectomy and ulcerative colitis (UC) and the majority of the studies support a highly significant inverse relationship.3 It is also well established that the protective effect of appendectomy depends on the inflammatory conditions (appendicitis or lymphadenitis) that were the indication for appendectomy rather than on appendectomy itself.4 The available data regarding whether or not appendectomy performed after the onset of UC can modulate its clinical course arey still limited and conflicting and properly controlled trials are needed.5 Despite accumulating clinical evidence, the mechanism linking appendicitis, appendectomy and UC remains elusive.

Interestingly, a link between Fusobacteria and UC has been reported in several studies. In 2002, F varium was reported to be present in the colonic mucosa of a high proportion (84%) of UC patients.6 Using immunoblotting with a F varium antigen Minami et al found positive signals with sera from 45 (40.2%) of 112 UC patients versus 20 (15.6%) of 128 healthy controls (p<0.01). Seropositive UC patients were more likely to have clinically severe disease than seronegative UC patients and the disease location in seropositive patients was more extensive than in seronegative patients.7 Finally, a 2-week triple antibiotic therapy to which F varium is susceptible (tetracycline, metronidazole and amoxicillin) produced improvement, remission and steroid withdrawal in active UC more effectively than a placebo.8

In conclusion, the development of an appendiceal dysbiosis may be a priming event in the occurrence of UC. The removal of the appendix may reduce the risk of further development of UC in genetically susceptible individuals. We believe that this hypothesis should be further explored in studies examining the protective role of appendicitis and appendectomy in UC.

References

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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