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Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation

ABSTRACT: Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation

PROVIDER: PRJNA875301 | ENA |

REPOSITORIES: ENA

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Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [metagenome]

Project description:Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [metagenome]

| PRJNA875303 | ENA

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [16s]

Project description:Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [16s]

| PRJNA877488 | ENA

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [Cep]

Project description:Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [Cep]

| PRJNA877585 | ENA

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [Feces]

Project description:Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [Feces]

| PRJNA877619 | ENA

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [gene expression]

Project description:Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [gene expression]

| PRJNA875304 | ENA

Transepithelial Barrier Dysfunction Drives Microbiota Dysbiosis to Initiate Epithelial Clock-driven Inflammation.

Project description:BackgroundFactors that contribute to inflammatory bowel disease [IBD] pathogenesis include genetic polymorphisms, barrier loss, and microbial dysbiosis. A major knowledge gap exists in the origins of the colitogenic microbiome and its relationship with barrier impairment. Epithelial myosin light chain kinase [MLCK] is a critical regulator of the paracellular barrier, but the effects of MLCK activation on the intraepithelial bacteria [IEB] and dysbiosis are incompletely understood. We hypothesise that MLCK-dependent bacterial endocytosis promotes pathobiont conversion and shapes a colitogenic microbiome.MethodsTo explore this, transgenic [Tg] mice with barrier loss induced by intestinal epithelium-specific expression of a constitutively active MLCK were compared with wild-type [WT] mice.ResultsWhen progeny of homozygous MLCK-Tg mice were separated after weaning by genotype [Tg/Tg, Tg/WT, WT/WT], increased IEB numbers associated with dysbiosis and more severe colitis were present in Tg/Tg and Tg/WT mice, relative to WT/WT mice. Cohousing with MLCK-Tg mice induced dysbiosis, increased IEB abundance, and exacerbated colitis in WT mice. Conversely, MLCK-Tg mice colonised with WT microbiota at birth displayed increased Escherichia abundance and greater colitis severity by 6 weeks of age. Microarray analysis revealed circadian rhythm disruption in WT mice co-housed with MLCK-Tg mice relative to WT mice housed only with WT mice. This circadian disruption required Rac1/STAT3-dependent microbial invasion but not MLCK activity, and resulted in increased proinflammatory cytokines and glucocorticoid downregulation.ConclusionsThe data demonstrate that barrier dysfunction induces dysbiosis and expansion of invasive microbes that lead to circadian disruption and mucosal inflammation. These results suggest that barrier-protective or bacterium-targeted precision medicine approaches may be of benefit to IBD patients.

| S-EPMC10588795 | biostudies-literature

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-08-31 | GSE212395 | GEO

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [metagenome]

Project description:A time-series alteration in fecal microbiota was linked to the emergence of intraepithelial bacteria and a unique transcriptome profile in the mouse colon during IBD development.

2025-08-31 | GSE212393 | GEO

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [Cep]

Project description:A time-series alteration in intestine epithelial microbiota was linked to the emergence of intraepithelial bacteria and a unique transcriptome profile in the mouse colon during IBD development.

2025-09-04 | GSE212822 | GEO

Transepithelial barrier dysfunction drives microbiota dysbiosis to initiate epithelial clock-driven inflammation [16s]

2025-09-04 | GSE212813 | GEO