Mucosal host–microbe interactions associate with clinical phenotypes in inflammatory bowel disease

Hu, Shixian; Bourgonje, Arno R.; Jansen, Bernadien H.; Björk, Johannes; Bangma, Amber; Hidding, Iwan J.; Dullemen, Hendrik M. van; Visschedijk, Marijn C.; Faber, Klaas Nico; Dijkstra, Gerard; Harmsen, Hermie J. M.; Festen, Eleonora A. M.; Vila, Arnau Vich; Spekhorst, Lieke M.; Weersma, Rinse K.

doi:10.1101/2022.06.04.494807

Cited by 3 publications

(2 citation statements)

References 161 publications

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“…A total of 711 intestinal biopsies were obtained from 420 patients diagnosed with IBD along with 52 intestinal biopsies from 16 healthy non-IBD controls (Hu et al , 2024). During an endoscopic procedure, biopsies were immediately frozen in liquid nitrogen by either an endoscopy nurse or a research technician.…”

Section: Methodsmentioning

confidence: 99%

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Morsink,

Koch,

et al. 2024

Preprint

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The intestinal mucous layer relies on mucin-2 secretion. While the mucin-2 secretory pathway has been studied, endoplasmic reticulum (ER) to Golgi apparatus (Golgi) trafficking remains poorly understood. The size of mucin-2 exceeds the capacity of regular coat protein complex II (COPII) vesicles, responsible for ER-to-Golgi transport. After confirming conventional secretion of mucin-2, we showed that COPII vesicle enlargement is facilitated by TANGO1 and cTAGE5, and promoted by KLHL12. Inflammatory bowel disease (IBD) is characterized by a compromised mucous layer, altered activity of Transforming Growth Factor beta (TGF-beta), and increased ER stress. Using a cell culture, we showed that TGF-beta inhibition induces TANGO1-mediated ER stress. Mucosal gene expression analysis in IBD patients confirmed elevated ER stress and validated concomitantly altered mRNA levels of TGF-beta with mucin-2 and transport proteins TANGO1 and cTAGE5. In conclusion, we propose that the unsuccessful formation of enlarged COPII vesicles could be a source of ER stress in IBD, because of lowered TANGO1 protein expression, subsequently leading to decreased mucin-2 secretion.

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Section: Methodsmentioning

confidence: 99%

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Morsink,

Koch,

et al. 2024

Preprint

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“…For the multivariate analysis, we employed sparse canonical correlation analysis (sparse-CCA), a powerful technique that has been successfully utilized to integrate diverse biological layers (37,38). This approach allowed us to identify coordinated patterns of associations between antibody profiles and inflammation-related markers.…”

Section: Viral Infections Associate With Circulating Inflammation-rel...mentioning

confidence: 99%

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Andreu-Sánchez,

Ripoll-Cladellas,

Culinscaia

et al. 2024

Preprint

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Prior encounters with pathogens and other molecules can imprint long-lasting effects on our immune system, potentially influencing future physiological outcomes. However, given the wide range of pathogens and commensal microbes to which humans are exposed, their collective impact on the health and aging processes in the general population is still not fully understood. In this study, we aimed to explore relations between exposures, including to pathogens, microbiome and common allergens, and biological aging and inflammation. We capitalized on an extensive repository of the antibody-binding repertoire against 2,815 microbial, viral, and environmental peptides in a deeply-phenotyped population cohort of 1,443 participants. Utilizing antibody-binding as a proxy for past exposures, we investigated their impact on biological aging markers, immune cell composition and systemic inflammation. This identified that immune response against cytomegalovirus (CMV), rhinovirus and specific gut bacterial species influences the telomere length of different immune cell types. Using blood single-cell RNA-seq measurements, we identified a large effect of CMV infection on the transcriptional landscape of specific immune cells, in particular subpopulations of CD8 and CD4 T-cells. Our work provides a broad examination of the role of past and chronic exposures in biological aging and inflammation, highlighting a role for chronic infections (CMV and Epstein-Barr Virus) and common pathogens (rhinoviruses and adenovirus C).

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Faecalibacterium prausnitzii promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway

Fagundes,

Bravo-Ruiseco,

et al. 2023

Front. Microbiol.

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IntroductionIntestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1α (HIF1α) pathway in regulating mucosal IL18 expression in inflammatory bowel disease (IBD).MethodsMucosal samples from patients with IBD (n = 760) were analyzed for bacterial composition, IL18 levels and HIF1α pathway activation. Wild-type Caco-2 and CRISPR/Cas9-engineered Caco-2-HIF1A-null cells were cocultured with Faecalibacterium prausnitzii in a “Human oxygen-Bacteria anaerobic” in vitro system and analyzed by RNA sequencing.ResultsMucosal IL18 mRNA levels correlated positively with the abundance of mucosal-associated butyrate-producing bacteria, in particular F. prausnitzii, and with HIF1α pathway activation in patients with IBD. HIF1α-mediated expression of IL18, either by a pharmacological agonist (dimethyloxallyl glycine) or F. prausnitzii, was abrogated in Caco-2-HIF1A-null cells.ConclusionButyrate-producing gut bacteria like F. prausnitzii regulate mucosal IL18 expression in a HIF1α-dependent manner that may aid in mucosal healing in IBD.

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Mucosal host–microbe interactions associate with clinical phenotypes in inflammatory bowel disease

Cited by 3 publications

References 161 publications

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Faecalibacterium prausnitzii promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway

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