P059 Indoleamine 2,3-Dioxygenase 1 Expression Promotes Epithelial Secretory Cell Differentiation via Aryl Hydrocarbon Receptor

Alvarado, David M.; Santhanam, Srikanth; Iticovici, Micah; Chen, Baosheng; Ciorba, Matthew A.

doi:10.1053/j.gastro.2017.11.097

Cited by 1 publication

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“…Normal pregnancy is a state of low-grade inflammation, specifically at gut mucosal surfaces and tissues like adipose with a build-up of proinflammatory cytokines 5,23 and inflammation upregulates IDO1 expression in the intestinal epithelium 24 . Thus, we assessed mRNA expression of cytokine genes in G0 and G15 ileum and distal colon (DC) mucosa.…”

Section: Low Grade Inflammation In Pregnancy Modulates Gut Ido1 Activitymentioning

confidence: 99%

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

Priyadarshini

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Reiman³

et al. 2021

Preprint

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Background and aims: Normal gestation involves reprogramming of maternal gut microbiome (GM) that may contribute to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM maternal metabolism interaction. Methods: The GM and plasma metabolome of CD1, NIH Swiss and C57BL/6J mice were analyzed using 16S rRNA sequencing and untargeted LC-MS throughout gestation and postpartum. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM in the process was studied using fecal microbial transplants (FMT). Results: Significant variation in gut microbial alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time-point specific, with species enriched at gestation day 15/19 (G15/19), a point of heightened IR, distinct from those enriched pre- or post-pregnancy. Untargeted and targeted metabolomics revealed elevated plasma kynurenine at G15/19 in all three mouse strains. IDO1, the rate limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine levels effects on IR derive from the GM in both mouse and human pregnancy. Conclusions: GM changes accompanying pregnancy shift IDO1 dependent tryptophan metabolism toward kynurenine production, intestinal inflammation and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1.

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Section: Low Grade Inflammation In Pregnancy Modulates Gut Ido1 Activitymentioning

confidence: 99%

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

Priyadarshini

Navarro

Reiman³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

P059 Indoleamine 2,3-Dioxygenase 1 Expression Promotes Epithelial Secretory Cell Differentiation via Aryl Hydrocarbon Receptor

Cited by 1 publication

References 0 publications

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

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