(455) Serotonin/tryptophan pathway disruption by maternal high fat diet exposure in non-human primate offspring gut

Thursday, February 9, 2023

4:00 PM – 5:30 PM

Objective: Gut microbes provide precursors to gut-produced neurotransmitters (serotonin, dopamine) and directly produce metabolites (GABA, short chain fatty acids/SCFAs, histamine) that are crucial for normal lifelong behavior via the gut-brain axis. In a Japanese macaque primate model, offspring exposed to maternal high fat diet (mHFD) display persistent, non-modifiable behavioral changes and gut microbiome composition compared to offspring exposed to maternal control diet (mCTR). We hypothesized that mHFD feeding, independent of obesity, would alter the offspring’s gut neurometabolome profile in vivo and would be persistent through 3 years of age.

Study Design: Dams were fed mHFD, mCTR, or a mHFD-to-mCTR reversal diet during pre-pregnancy, gestation, and lactation (Fig 1). Offspring were weaned at 6 months. Serum and fresh stool were collected longitudinally. Intestine was collected at necropsy (fetal, 1yr., 3yr.). The tissues were analyzed by LC-MS targeting metabolites of known behavioral neuroactive pathways (serotonin, GABA, dopamine), histamine, and SCFAs.

Results: We measured 34 neuroactive metabolites in n=303 serum, n=390 stool, and n=519 intestinal samples from n=72 fetal and n=134 juvenile offspring. Fetal serum and intestine (Fig 2A-B) displayed few differences in response to mHFD feeding. In juveniles weaned onto HFD, mHFD exposure drove an altered global stool metabolomic profile of the known neuropathways (Fig 2D). When juveniles are weaned onto CTR, serotonin/tryptophan, histamine, and SCFA pathways drive the altered global stool metabolomic profile (Fig 2E) with intestinal serotonin/tryptophan and SCFA pathways being of significance regardless of the post-weaning diet (Fig 2C,F,G).

Conclusion: We showed that mHFD feeding drives alterations of the gut serotonin/tryptophan and SCFA pathways in 1 yr. and 3 yr. old offspring that are not improved by weaning onto a control diet. Gut microbes can alter these neurometabolic pathways, and therefore the offspring’s gut microbiome warrants attention in the context of the effects of maternal diet in humans, mice, and primates.

Primary & Presenting Author(s)

Erin Bolte, MSc (she/her/hers)
MD/PhD Student
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine
Houston, Texas, United States

Coauthor(s)

TH
Thomas Horvath, PhD
Texas Children’s Microbiome Center Mass Spectrometry Laboratory, Texas Children’s Hospital
Houston, Texas, United States
Maxim D. Seferovic, PhD
Assistant Professor
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital
Houston, Texas, United States
SH
Sigmund Haidacher, BS
Texas Children's Hospital
Houston, Texas, United States
KH
Kathleen Hoch, BA
Texas Children's Hospital
Houston, Texas, United States
Derek O'Neil, PhD
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital
Houston, Texas, United States
AH
Anthony Haag, PhD
Texas Children’s Microbiome Center Mass Spectrometry Laboratory, Texas Children’s Hospital
Houston, Texas, United States
Kjersti M. Aagaard, MD,PhD
Professor and Vice Chair of Research Department of Obstetrics and Gynecology, Division of MFM
Texas Children's and Baylor College of Medicine
Houston, Texas, United States