Microorganisms to the rescue: The use of a probiotic treatment to reduce developmental vulnerability in rats

Abstract

Recent findings have revealed that the community of microorganisms residing within the gastrointestinal tract, collectively known as the gut microbiota, is not only far more complex than previously imagined but also fundamental to physical and mental health. This has prompted a rapid expansion of cross-disciplinary research into the gut-brain axis. Within this emerging field, few have investigated the impact of microbiota manipulations on psychological functioning during development. In this thesis, the effects of a probiotic formulation (composed of Lactobacillus [L.] helveticus and L. rhamnosus and administered via the maternal drinking water) on behavioural, neural, and physical development was tested in rats exposed to early-life stress (daily, 3-hour bouts of maternal separation on postnatal days 2-14).

The first series of experiments, described in Chapter 2, examined potential routes of transmission for probiotic effects on infant behaviour. No effects of treatment were observed for maternal behaviour. However, physical transfer of the probiotic species to maternally-separated (MS) infants was detected, suggesting that direct bacterial exposure is important for probiotic treatment effects.

The experiments described in Chapter 3 investigated the impact of MS and probiotics on development of neural circuits supporting emotional learning. Stress accelerated maturation of neural function in male infants, but this effect was prevented by probiotic exposure.

In Chapter 4 I examined physical maturation in MS rats. Stress accelerated puberty development in females and slowed puberty development in males, but probiotic exposure restored the normative timing of puberty onset in both sexes.

The final series of experiments (Chapter 5) explored the impact of probiotic treatment for the offspring of stressed male rats. Probiotics administered during the father’s exposure to stress or during his offspring’s infancy prevented the generational transmission of stressed behavioural phenotypes (i.e., extended fear retention and relapse-prone extinction during infancy).

Together, these studies provide striking support for the use of probiotics to prevent alterations in behavioural, neural, and physical development for individuals exposed to early-life stress and their offspring. The clinical and theoretical implications of these findings are discussed in light of our current understanding of the effects of stress on development and the gut-brain axis.