# Maternal diet and programming of offspring gut-brain axis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $537,125

## Abstract

Obesity continues to rise worldwide. Maternal obesity and consumption of high calorie diets
continue to be public health concerns. The intrauterine and early postnatal environment
provides support that is critical to the proper development and health of offspring. Maternal high
fat (HF) diet consumption during pregnancy can have persistent detrimental effects on the fetus
that predispose to obesity and its comorbidities. Our preliminary data in a rat model suggest that
maternal HF diet has negative consequences on offspring controls of food intake via the gut-
brain axis. Our overarching hypothesis is that gut dysbiosis resulting from perinatal exposure to
maternal HF diet alters development of the gut-brain axis and vagally-mediated controls of
feeding in offspring leading to increased susceptibility to obesity and other metabolic disorders.
Aim 1 will determine how vagally-mediated controls of feeding are altered in rat offspring from
dams consuming a HF during pregnancy and lactation. We hypothesize that HF offspring will be
less sensitive to peripheral gut hormones, meal pre-loads, and/or nutrients that normally
promote satiety. Aim 2 will determine how vagal communication between the gut and the brain
is altered in HF offspring. We hypothesize that decreased satiation responses occur because
(a) there is an alteration in the structure of VAN projections from the gut to the brain, (b) deficits
in enteroendocrine cell number or function, and/or (c) the vagus nerve is less responsive to gut
feedback signals. Aim 3 will define the role of gut microbiota composition in HF offspring
propensity to obesity and other metabolic disorders. Our preliminary data indicate that HF
offspring have gut dysbiosis and greater intestinal permeability by the time that they are weaned
at postnatal day 21. Dysbiosis is sufficient to alter vagal structure and function, therefore we
hypothesize that gut dysbiosis in HF offspring negatively affects gut-brain axis development and
function. We will transfer dysbiotic HF microbiota to germ-free neonates to test sufficiency of
dysbiosis in altered gut-brain axis function and determine whether use of prebiotics to normalize
microbiota composition of HF fed dams, and consequently their offspring, will improve offspring
gut-brain axis development and function. Together the proposed experiments will identify
components of the gut-brain axis that are altered by early life exposure to maternal HF diet and
could be targets for intervention to prevent adverse long-term metabolic consequences in HF
offspring.

## Key facts

- **NIH application ID:** 10835112
- **Project number:** 5R01DK129193-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** KELLIE L. K. TAMASHIRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $537,125
- **Award type:** 5
- **Project period:** 2022-06-30 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835112

## Citation

> US National Institutes of Health, RePORTER application 10835112, Maternal diet and programming of offspring gut-brain axis (5R01DK129193-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10835112. Licensed CC0.

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