Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3:71:76-82. doi: 10.1016/j.pnpbp.2016.06.010. Epub 2016 Jun 21.

Abstract

Background: A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice.

Objective: To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previously been shown to substantially perturb the gut microbiota in rats following a 28-day exposure.

Methods: Female Wistar rats were divided in two groups: control, or exposed during one month before breeding until gestational day 15 to a diet containing 1% SST. We administered behavioral tests to offspring, i.e., open field (post-natal day 20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensory gating) (P45).

Results: Both male and female offspring exposed peri-conceptionally to SST showed reduced social interactions, with a decrease of about half in time spent in social interactions compared to controls, reduced exploration of the open arm by 20% in the elevated plus maze test indicating increased anxiety and altered sensorimotor gating, with a 1.5-2-fold decrease in startle inhibition.

Conclusion: Maternal periconceptional exposure to SST provokes alterations in offspring behavior in the absence of maternal infection. Because we administered SST, a non-absorbable antibiotic, only to the dam, we conclude that these neurobehavioral alterations in the offspring are related to maternal gut microbiota alterations.

Keywords: Antibiotic; Behavior; Microbiota; Rat; SuccinylSulfaThiazole.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Animals, Newborn
  • Anti-Infective Agents / adverse effects*
  • Anxiety / etiology*
  • Eating / drug effects
  • Exploratory Behavior / drug effects
  • Female
  • Homocysteine / metabolism
  • Interpersonal Relations*
  • Male
  • Maze Learning / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Prenatal Exposure Delayed Effects* / psychology
  • Prepulse Inhibition / drug effects
  • Rats
  • Rats, Wistar
  • Sulfathiazoles / adverse effects*
  • Tryptophan / metabolism

Substances

  • Anti-Infective Agents
  • Sulfathiazoles
  • Homocysteine
  • Tryptophan
  • succinylsulfathiazole