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Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn's disease.
Am J Physiol Gastrointest Liver Physiol. 2018 09 01; 315(3):G420-G431.AJ

Abstract

Crohn's disease (CD), characterized by discontinuous intestinal injury and inflammation, has been associated with changes in luminal microbial composition and impaired barrier function. The relationships between visual features of intestinal injury, permeability, and the mucosa-associated microbiota are unclear. Individuals undergoing routine colonoscopy (controls) and patients with CD were evaluated by clinical parameters and confocal laser scanning endomicroscopic colonoscopy (CLE). Patients with CD were categorized as either CD with no injury (CD-NI) or CD with injury (CD-I). Colonic biopsies were taken from adjacent matched sites in all individuals, and CLE images from these sites were analyzed for vascular permeability. Microbial composition was evaluated by 16S rRNA gene sequencing of the V3 region, and the mycome was identified through internal transcribed spacer 2 sequencing. Subgroup analyses were performed for histology, paracellular permeability (Ussing chamber), and encroachment of bacteria (fluorescent in situ hybridization). CD-I patients showed an altered microbial community compared with both controls and CD-NI patients, with enrichment in Escherichia and a decrease in Firmicutes, including Lachnospira, Faecalibacterium, and Blautia. In CD-I patients, bacterial encroachment to host epithelial cells was greater in sites of injury than in matched biopsy sites. Biopsies from sites of injury also demonstrated greater vascular and paracellular permeability. Overall, CD-I patients showed an altered mucosal microbial community compared with CD-NI patients and controls. Matched biopsy samples in CD-I patients revealed that sites of injury, identified endoscopically, are characterized by increased encroachment of bacteria to host epithelial cells, associated with increased paracellular and vascular permeability, which may drive inflammation in CD. NEW & NOTEWORTHY Patients with Crohn's disease (CD) with areas of colonic injury have an altered microbial community compared with patients who have no endoscopic evidence of injury or active disease. Although matched biopsies from patients with colonic injury show no differences in the mucosa-associated microbiota, injured sites are associated with increased permeability and increased encroachment. Our results support the notion that dysbiotic communities within patients with colonic injury cause or permit disruption of the mucosal and endothelial layers in CD.

Authors+Show Affiliations

Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario , Canada. Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada.Department of Gastroenterology, Postgraduate Institute of Medical Education and Research , Chandigarh , India.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario , Canada. Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario , Canada.Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario , Canada. Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario , Canada. Department of Medicine, McMaster University , Hamilton, Ontario , Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29848021

Citation

Libertucci, Josie, et al. "Inflammation-related Differences in Mucosa-associated Microbiota and Intestinal Barrier Function in Colonic Crohn's Disease." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 315, no. 3, 2018, pp. G420-G431.
Libertucci J, Dutta U, Kaur S, et al. Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn's disease. Am J Physiol Gastrointest Liver Physiol. 2018;315(3):G420-G431.
Libertucci, J., Dutta, U., Kaur, S., Jury, J., Rossi, L., Fontes, M. E., Shajib, M. S., Khan, W. I., Surette, M. G., Verdu, E. F., & Armstrong, D. (2018). Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn's disease. American Journal of Physiology. Gastrointestinal and Liver Physiology, 315(3), G420-G431. https://doi.org/10.1152/ajpgi.00411.2017
Libertucci J, et al. Inflammation-related Differences in Mucosa-associated Microbiota and Intestinal Barrier Function in Colonic Crohn's Disease. Am J Physiol Gastrointest Liver Physiol. 2018 09 1;315(3):G420-G431. PubMed PMID: 29848021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn's disease. AU - Libertucci,Josie, AU - Dutta,Usha, AU - Kaur,Sandeep, AU - Jury,Jennifer, AU - Rossi,Laura, AU - Fontes,Michelle E, AU - Shajib,M Sharif, AU - Khan,Waliul I, AU - Surette,Michael G, AU - Verdu,Elena F, AU - Armstrong,David, Y1 - 2018/05/31/ PY - 2018/6/1/pubmed PY - 2019/7/5/medline PY - 2018/6/1/entrez KW - crohn's disease KW - dysbiosis KW - microbiota KW - permeability SP - G420 EP - G431 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 315 IS - 3 N2 - Crohn's disease (CD), characterized by discontinuous intestinal injury and inflammation, has been associated with changes in luminal microbial composition and impaired barrier function. The relationships between visual features of intestinal injury, permeability, and the mucosa-associated microbiota are unclear. Individuals undergoing routine colonoscopy (controls) and patients with CD were evaluated by clinical parameters and confocal laser scanning endomicroscopic colonoscopy (CLE). Patients with CD were categorized as either CD with no injury (CD-NI) or CD with injury (CD-I). Colonic biopsies were taken from adjacent matched sites in all individuals, and CLE images from these sites were analyzed for vascular permeability. Microbial composition was evaluated by 16S rRNA gene sequencing of the V3 region, and the mycome was identified through internal transcribed spacer 2 sequencing. Subgroup analyses were performed for histology, paracellular permeability (Ussing chamber), and encroachment of bacteria (fluorescent in situ hybridization). CD-I patients showed an altered microbial community compared with both controls and CD-NI patients, with enrichment in Escherichia and a decrease in Firmicutes, including Lachnospira, Faecalibacterium, and Blautia. In CD-I patients, bacterial encroachment to host epithelial cells was greater in sites of injury than in matched biopsy sites. Biopsies from sites of injury also demonstrated greater vascular and paracellular permeability. Overall, CD-I patients showed an altered mucosal microbial community compared with CD-NI patients and controls. Matched biopsy samples in CD-I patients revealed that sites of injury, identified endoscopically, are characterized by increased encroachment of bacteria to host epithelial cells, associated with increased paracellular and vascular permeability, which may drive inflammation in CD. NEW & NOTEWORTHY Patients with Crohn's disease (CD) with areas of colonic injury have an altered microbial community compared with patients who have no endoscopic evidence of injury or active disease. Although matched biopsies from patients with colonic injury show no differences in the mucosa-associated microbiota, injured sites are associated with increased permeability and increased encroachment. Our results support the notion that dysbiotic communities within patients with colonic injury cause or permit disruption of the mucosal and endothelial layers in CD. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/29848021/Inflammation_related_differences_in_mucosa_associated_microbiota_and_intestinal_barrier_function_in_colonic_Crohn's_disease_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00411.2017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -