Influence of Maternal Diet on the Tight Junction Remodeling in Baboon Offspring

Author(s):
Alena Golubkova; Heather Liebe; Tyler Leiva; James Papin; Jed Friedman; Dean Myers; Catherine Hunter

Background:

Obesity and diets rich in saturated fats and sugars have been implicated in gastrointestinal disease, including increased susceptibility to infection. It is proposed that this occurs through molecular remodeling of the gut barrier as well as increased inflammation and compromised immunity. The effect of maternal obesity and diet on offspring gut is currently being investigated.

Hypothesis:

We studied the influence of a maternal Western diet on offspring gut in the Olive baboon, hypothesizing that it would lead to offspring changes suggestive of increased gut permeability through changes seen in tight junction composition.

Methods:

Ileal samples were collected from an IACUC-approved study investigating influence of maternal diet on offspring. Adult, nulliparous female baboons were fed a Western diet (WSD) and a Control diet of monkey chow. Three months after initiation, baboons were bred. Cesarean sections were completed at 165 ±5 days, and the offspring were euthanized for necropsy and tissue collection. Mother’s adiposity (skin fold measurements) and CRP levels were obtained to measure inflammation. Protein and gene expression of select tight junction components, claudin 1, 2, 3, and occludin, was analyzed. Comparison was carried out with Student’s t-test.

Results:

There was no difference between maternal adiposity at time of cesarean. Maternal CRP was elevated in WSD group (p=0.009). A tight junction protein, claudin-1, appeared to have a down trend in RNA and protein expression, although not significant. No other changes suggestive of compromised gut barrier were noted.

Conclusions:

Maternal diets rich in saturated fats and sugar have been implicated in changes to neonatal gut immunity and microbiome. We aimed to determine evidence of this by investigating for potential changes in tight junction composition with a translational baboon model. In our study, the maternal exposure time of WSD was insufficient to induce significant obesity in mothers but did increase maternal CRP. Longer maternal exposure times to the diet and larger study numbers in future offspring will potentially delineate if any significant changes do occur to lead to increased gut permeability and in turn susceptibility to infection.