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High‐fat diet intake modulates maternal intestinal adaptations to pregnancy, and results in placental hypoxia and altered fetal gut barrier proteins and immune markers

Gohir W, Kennedy KM, Wallace JG, Saoi M, Bellissimo CJ, Britz-McKibbin P, Petrik JJ, Surette MG, Sloboda DM (2019) J Physiol.  2019 May.  doi: 10.1113/JP277353. [Epub ahead of print] 

Web URL: Read this and related abstracts on PubMed here


Maternal obesity has been associated with shifts in intestinal microbiota which may contribute to impaired barrier function Impaired barrierfunction may expose the placenta and fetus to pro-inflammatory mediators.

We investigated the impacts of 
diet-induced obesity in mice on maternal and fetal intestinal structure and placental vascularization Diet-induced obesity decreased maternal intestinal short chain fatty acids, their receptors, impaired gut barrier integrity and was associated with fetal intestinal inflammation. Placenta from obese mothers showed blood vessel immaturity, hypoxia, increased transcript levels of inflammation, autophagy and ER stress markers.

These data suggest that 
maternal intestinal changes likely contribute to adverse placental adaptations and, via alterations in fetal gut development, impart increased risk of obesity in the offspring ABSTRACT: Shifts in maternal intestinal microbiota have been implicated in metabolic adaptations to pregnancy.

In this study we generated cohorts of female C57BL/6J mice fed a control (17% kcal fat, n = 10-14) or a 
high-fat diet (HFD 60% kcal from fat, n = 10-14; ad libitum) to investigate impacts on the maternal gut microbiota, intestinal inflammation and gut barrier integrity, placental inflammation, and fetal intestinal development at E18.5.

HFD was associated with decreased relative abundances of SCFA producing genera during 
pregnancy. These diet-induced shifts paralleled decreased maternal intestinal mRNA levels of SCFA receptor Gpr41, modestly decreased cecal butyrate, and altered mRNA levels of inflammatory cytokines and immune cell markers in the maternal intestine. 

Maternal HFD resulted in impaired gut barrier integrity, with corresponding increases in circulating maternal levels of LPS and TNF. Placenta from HFD dams demonstrated blood vessel immaturity and hypoxia, decreased free carnitine, acylcarnitine derivatives, TMAO, as well as altered mRNA levels of inflammation, autophagy and ER stress markers. HFD exposed fetuses had increased activation of NF-κB and inhibition of the unfolded protein response in the developing intestine.

Together, these data suggest that HFD 
intake prior to and during pregnancy shifts the composition of the maternal gut microbiota and impairs gut barrier integrity, resulting in increased maternal circulating LPS, which may ultimate contribute to changes in placental vascularization and fetal gut development.


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