IBD—what role do Proteobacteria play?

Abstract

The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial diversity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. Individual Proteobacteria, in particular (adherent-invasive) Escherichia coli, Campylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.

Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression

“…Our finding of a striking increase of unique bacterial taxa in the family Comamonadaceae (phylum Proteobacteria) in weanling mice deprived of passive SIgA may be significant in light of the report documenting increased numbers of Comamonadaceae in the microbiota of IBD patients with chronic pouchitis (33). Expansion of Proteobacteria has consistently been reported in the gut microbiota of adult IBD patients (34), suggesting that dysbiosis that develops early in life may persist throughout life.…”

QseC inhibition as an antivirulence approach for colitis-associated bacteria

“…Enterobacteriaceae can increase their colitogenic potential under inflammatory conditions and may participate in initiating and potentiating inflammation in IBD (1,(38)(39)(40). LED209 studies measuring pathogen growth and survival in vitro and in infection models suggest that this antivirulence approach can reduce pathogenicity without affecting bacterial growth (21).…”

“…This approach would allow us to explore the translational applicability of a QseC-targeted antivirulence strategy for IBD. We hypothesized that LED209 may reduce disease activity, given that the Enterobacteriaceae family and Proteobacteria phylum have been implicated in instigating and/or perpetuating intestinal inflammation in preclinical colitis models (38). Thus, LED209 was administered daily to SPF T-bet −/− Rag2 −/− , Il10 −/− , and DSS-treated WT mice.…”

Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis

“…Th e published evidence to date has relied on largely opportunistic studies of patients with established disease, providing a microbial snapshot of the chronic disease state at various time points aft er diagnosis. A signifi cant limitation of this approach however is that the major confounders of active treatment and disease chronicity make it impossible to interpret events following on from disease initiation ( 12 ). Th e interrogation of the fecal microbiota in many studies also introduces a diffi culty, as the mucosal and fecal bacterial ecosystems are recognized as being distinct in health, but with little known in disease states ( 13,14 ).…”