Bacterial Translocation as Inflammatory Driver in Crohn's Disease.
Crohn’s disease
NOD2
anti-TNF-α
bacterial translocation
dysbiosis
inflammatory response
intestinal permeability
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
04
2021
accepted:
30
07
2021
entrez:
24
9
2021
pubmed:
25
9
2021
medline:
25
9
2021
Statut:
epublish
Résumé
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract responsible for intestinal lesions. The multifactorial etiology attributed to CD includes a combination of environmental and host susceptibility factors, which result in an impaired host-microbe gut interaction. Bacterial overgrowth and dysbiosis, increased intestinal barrier permeability, and altered inflammatory responses in patients with CD have been described in the past. Those events explain the pathogenesis of luminal translocation of bacteria or its products into the blood, a frequent event in CD, which, in turn, favors a sustained inflammatory response in these patients. In this review, we navigate through the interaction between bacterial antigen translocation, permeability of the intestinal barrier, immunologic response of the host, and genetic predisposition as a combined effect on the inflammatory response observed in CD. Several lines of evidence support that translocation of bacterial products leads to uncontrolled inflammation in CD patients, and as a matter of fact, the presence of gut bacterial genomic fragments at a systemic level constitutes a marker for increased risk of relapse among CD patients. Also, the significant percentage of CD patients who lose response to biologic therapies may be influenced by the translocation of bacterial products, which are well-known drivers of proinflammatory cytokine production by host immune cells. Further mechanistic studies evaluating cellular and humoral immune responses, gut microbiota alterations, and genetic predisposition will help clinicians to better control and personalize the management of CD patients in the future.
Identifiants
pubmed: 34557484
doi: 10.3389/fcell.2021.703310
pmc: PMC8452966
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
703310Informations de copyright
Copyright © 2021 Linares, Francés, Gutiérrez and Juanola.
Déclaration de conflit d'intérêts
AG has served as speaker, consultant, or advisory member for, or received research funding from MSD, ABBVIE, TAKEDA, KERN PHARMA, PFIZER, OTSUKA, SHIRE, and JANSSEN, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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