Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn’s disease

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.

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets

“…This may partially explain the enhanced expression of ZO-1 and claudin-1, since the overproduction of IL-6 and TNF-α was considered to participate in enhancing intestinal epithelial permeability [ 34 ]. Recent studies suggested that intestinal inflammation might be associated with microbial composition changes [ 20 ]. AUR can inhibit the growth of pathogenic bacteria like Escherichia-Shigella, which can cause intestinal inflammation through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signal pathways [ 35 , 36 ].…”

“…In the present study, dietary supplementation of PCA increased the Firmicutes/Bacteroidetes ratio, in which Firmicutes are more effective as an energy source than Bacteroidetes in promoting more efficient absorption of calories [ 5 , 37 ]. Furthermore, the decrease in the phylum Firmicutes was also observed in Crohn’s disease patients [ 20 ], and Firmicutes are considered as one of the producers of short-chain fatty acid (SCFA) [ 38 ].…”

“…Previous studies have reported that PCA possesses antioxidant [ 15 ], anti-inflammatory [ 16 ], antibacterial [ 17 ] and antiviral [ 18 ] effects and has the potential to attenuate intestinal injury [ 9 , 19 ]. Meanwhile, intestinal flora disturbance is reported to be associated with intestinal injury, inflammation, and impaired barrier function [ 20 ], and our previous study has indicated that polyphenols may exert beneficial biological functions by regulating the gut microbial community [ 5 ]. Thus, in the present study, we challenged to clarify the effect of PCA on gut microbiota and their correlation with intestinal barrier function in lipopolysaccharide (LPS)-challenged weaned piglets.…”

Microbiota in the Gastrointestinal Tract

“…Interestingly, the determination of mucosal bacteria from injured sites of patients with CD show increased numbers of Escherichia (phylum Proteobacteria) but reduced proportions of Lachnospira , Faecalibacterium , and Blautia , all belonging to phylum Firmicutes, as compared to biopsies from adjacent mucosal sites without injury. The dysbiosis is suggested to favor or maintain endothelial lesions in CD [27]. Recently, a dysbiosis and invasion of bacteria has also been described in the gut of patients with ankylosing spondylitis.…”

Healthy Protection Of Bergamot Is Linked To The Modulation Of Microbiota

“…Blautia, involved in complex carbohydrate digestion, is recognized as a good indicator of the intestinal health, and its increase is bene cial. On the contrary, a Blautia reduction was observed in patients affected by heart failure [23], by hepatic and Chron's disease, and cancer [24][25][26]. Very interestingly, it has just been published that Blautia genus is inversely related with visceral fat accumulation [27].…”