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Recording

Oral Plenary Session II - Fellows Plenary and Late-Breaking

Oral Plenary Sessions

(14) Persistent Programming of Offspring Gut Serotonin Pathway by Maternal Western-Style Diet in Non-Human Primates

Tuesday, February 13, 2024
9:15 AM – 9:30 AM  
Location: Potomac Ballroom, Ballroom Level
Objective:

Anxiety is a mood disorder associated with low levels of serotonin. Over 95% of the body’s serotonin is produced in the gut by enterochromaffin cells, and it affects the brain and behavior via signaling at the vagus nerve (the gut-brain axis). We have previously shown that non-human primate offspring exposed to maternal Western-Style diet (WSD) display anxiety persistent into juvenile life. To investigate the connection between maternal WSD and serotonin as a mechanism for the observed anxiety, we hypothesized that maternal WSD can persistently program offspring gut enterochromaffin cells.

Study Design:

Macaques were fed WSD or Chow control diet during gestation/lactation. Offspring were sampled at fetal necropsy (late third-trimester, n=4) or born vaginally and weaned onto a Chow diet for sampling at 3 years of age (peripuberty, n=8) (Fig. 1A). Ex vivo intestinal organoids were generated from fresh descending colon biopsy tissue at both timepoints and differentiated to contain serotonin-producing enterochromaffin cells. Secreted serotonin and serotonin-related gene expression were measured.

Results:

Maternal WSD-programmed fetal and juvenile intestinal organoids secreted decreased serotonin compared to Chow control organoids (fetal 0.006 versus 0.011 pg/cells, p= 0.021, Fig. 1B; 3 year-olds 0.010 versus 0.014 pg/cells, p= 0.033, Fig. 1C). At the Fetal stage, maternal WSD-programmed intestinal organoids expressed increased enterochromaffin cell marker expression (CHGA p= 0.0004) and decreased serotonin transporter expression (SERT, p=0.0009), with no statistical difference in serotonin rate limiting enzyme expression (TPH1) (Fig. 1D).

Conclusion:

We have observed that maternal WSD exposure disrupts enterochromaffin cell secretion of serotonin in the colon beginning in fetal life. This disruption is not normalized by a normal offspring diet, as low serotonin secretion is still observed when offspring are 3-years-old. Maternal WSD programs an altered serotonin pathway gene expression equilibrium, which may predispose the gut-brain axis of these offspring towards anxiety.