Maternal diet and programming of offspring gut-brain axis

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Principal Investigator: KELLIE L. K. TAMASHIRO
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $96,351
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases

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.

Terms: <0-11 years old><21+ years old><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Affect><Afferent Neurons><Autoregulation><Behavior><Birth><Brain><Brain Nervous System><CCK><Calcium><Calories><Cancers><Cell Communication and Signaling><Cell Count><Cell Function><Cell Number><Cell Physiology><Cell Process><Cell Signaling><Cellular Function><Cellular Physiology><Cellular Process><Child><Child Youth><Children (0-21)><Cholecystokinin><Common Rat Strains><Communication><Consumption><Coronary Arteriosclerosis><Coronary Artery Disease><Coronary Artery Disorder><Coronary Atherosclerosis><Cranial Nerve X><Data><Development><Diet><Eating><Encephalon><Endocrine Gland Secretion><Energy consumption><Enteroendocrine Cell><Environment><Epidemic><Exposure to><Fat-Restricted Diet><Fats><Fatty acid glycerol esters><Feedback><Fetus><Food Intake><Future><GI microbiota><GWA study><GWAS><Gastrointestinal microbiota><Germ-Free><Gestation><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><Health><High Fat Diet><Homeostasis><Hormones><Hyperphagia><Hypertension><Image><Impairment><Individual><Inflammation><Inflammatory><Interdisciplinary Research><Interdisciplinary Study><Intervention><Intervention Strategies><Intestinal><Intestinal Epithelial Permeability><Intestinal Hyperpermeability><Intestinal Leakage><Intestinal permeability><Intestines><Intracellular Communication and Signaling><Ketosis-Resistant Diabetes Mellitus><Lactation><Leaky Gut><Life><Low-Fat Diet><Malignant Neoplasms><Malignant Tumor><Maternal Nutrition><Maternal diet><Maturity-Onset Diabetes Mellitus><Mediating><Metabolic><Metabolic Diseases><Metabolic Disorder><Metabolic dysfunction><Metabolic syndrome><Methods><Modeling><Mothers><Multidisciplinary Collaboration><Multidisciplinary Research><NIDDM><Nerve Cells><Nerve Impulse Transmission><Nerve Transmission><Nerve Unit><Neural Cell><Neurobiology><Neurocyte><Neuronal Transmission><Neurons><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nutrient><Obesity><Outcome><Over weight><Overeating><Overweight><Pancreozymin><Parturition><Pattern><Perinatal><Perinatal Exposure><Peripartum><Peripheral><Phenotype><Physiological Homeostasis><Pneumogastric Nerve><Predisposition><Pregnancy><Prevalence><Public Health><Rat><Rats Mammals><Rattus><Regulation><Resistance><Risk><Role><Satiation><Sensory><Sensory Neurons><Signal Transduction><Signal Transduction Systems><Signaling><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Starch><Stimulus><Structure><Subcellular Process><Susceptibility><T2 DM><T2D><T2DM><Tenth Cranial Nerve><Testing><Therapeutic Hormone><Thesaurismosis><Time><Tracer><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Uropancreozymin><Vagus Nerve><Vagus nerve structure><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Virus><Weaning><Weight Gain><Weight Increase><adiposity><adult onset diabetes><adulthood><atherosclerotic coronary disease><axon signaling><axon-glial signaling><axonal signaling><biological signal transduction><body weight gain><body weight increase><bowel><child adiposity><child obesity><childhood adiposity><childhood obesity><co-morbid><co-morbidity><combinatorial><comorbidity><coronary arterial disease><corpulence><critical period><develop therapy><developmental><diet-associated obesity><diet-induced obesity><diet-related obesity><diets><dysbacteriosis><dysbiosis><dysbiotic><early life exposure><enteric microbial community><enteric microbiota><experiment><experimental research><experimental study><experiments><feeding><gastrointestinal microbial flora><gene locus><genetic locus><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><genomic location><genomic locus><glia signaling><glial signaling><gut commensal><gut community><gut dysbiosis><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiota><gut microbiotic><gut microflora><gut to brain axis><gut-brain axis><gut-brain communication><gut-brain interactions><gut-brain relationship><gut-brain signaling><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><imaging><improved><innovate><innovation><innovative><intervention development><interventional strategy><intestinal crypt><intestinal flora><intestinal microbiota><intestinal microflora><intestinal tract microflora><ketosis resistant diabetes><kids><lack of physical activity><lactating><lactational><malignancy><maternal adiposity><maternal nutrition during pregnancy><maternal obesity><maturity onset diabetes><metabolism disorder><microbial consortia><microbial flora><microbial imbalance><microbiota><microbiota composition><microflora><mother nutrition><multispecies consortia><neonate><neoplasm/cancer><nerve signaling><neural><neural signaling><neurobiological><neuronal><neuronal signaling><neurotransmission><normal flora><normal microbial flora><normal microbiota><normal microflora><nutrition><obese children><obesity during childhood><obesity in children><offspring><pediatric obesity><perinatal environment><physical inactivity><polyphagia><post-natal period><postnatal><postnatal period><prebiotics><prevent><preventing><resistant><response><satiety><skills><social role><systemic inflammation><systemic inflammatory response><therapy development><translation to humans><treatment development><type 2 DM><type II DM><type two diabetes><whole genome association analysis><whole genome association studies><whole genome association study><wt gain><youngster>