Oral Concurrent Session 3 - Basic Science
Oral Concurrent Sessions
Thomas Horvath, PhD
Texas Children’s Microbiome Center Mass Spectrometry Laboratory, Texas Children’s Hospital
Houston, TX, United States
Maxim D. Seferovic, PhD
Assistant Professor
Baylor College of Medicine and Texas Children’s Hospital
Houston, TX, United States
Anthony Haag, PhD
Texas Children’s Microbiome Center Mass Spectrometry Laboratory, Texas Children’s Hospital
Houston, TX, United States
Kjersti M. Aagaard, MD, PhD
Professor and Vice Chair of Research Department of Obstetrics and Gynecology, Division of MFM
Texas Children's Hospital, Baylor College of Medicine
Houston, TX, United States
Maternal Western-Style diet (mWSD) feeding and obesity during pregnancy/breastfeeding have been linked to increased offspring anxiety. Anxiety is the result of decreased serotonin, an important neurotransmitter in mood regulation. Serotonin is synthesized from tryptophan and degraded into 5-hydroxyindoleacetic acid (5-HIAA). We hypothesized that mWSD feeding in a primate model would alter her offspring’s serotonin pathway metabolites, leading to persistent and evident offspring anxiety at 3 years of age (peripuberty).
Study Design:
Japanese macaque dams were fed a Chow control diet or mWSD during gestation and lactation, then offspring were weaned onto Chow or Western-Style diet (Fig. 1A). Anxiety was tested by multiple validated measures at 34 months and scored by blinded reviewers. Serum was collected at 36-40 months and analyzed by targeted liquid chromatography-mass spectrometry of all known serotonin pathway metabolites and other metabolites known to affect behavioral neuroactivity (gamma-aminobutyric acid and short-chain fatty acids).
Results:
Anxiety was calculated as the sum of four components: high energy outbursts and reactive, ritualized, and inactive behaviors (Fig. 1B). Total anxiety scores display a right shift (more frequent occurrence) in males (Z-test p= 0.005, Fig. 1C). We detected 18 neuroactive metabolites in serum which withstood confirmatory factor analysis, revealing statistically significant inverse relationships between 5-HIAA levels and ritualized anxiety (p=0.004) and high energy outbursts (p=0.048, Fig. 1D).
Conclusion:
We demonstrated that mWSD feeding programs male offspring with persistently increased anxiety, despite 2.5 years of control diet feeding. Analysis of serotonin metabolites showed an inverse correlation between 5-HIAA and anxiety, indicating low levels of serotonin inferred from its degradation product that correspond with higher levels of anxiety. These data underscore the importance of dietary counseling during pregnancy and lactation to potentially prevent unintended programming of offspring neuroactivity and anxiety behavior.