Neurobehavioural effects of Lactobacillus rhamnosus GG alone and in combination with prebiotics polydextrose and galactooligosaccharide in male rats exposed to early-life stress

Abstract

Early life is a period of significant brain development when the brain is at its most plastic and vulnerable. Stressful episodes during this window of development have long-lasting effects on the central nervous system. Rodent maternal separation (MS) is a reliable model of early-life stress and induces alterations in both physiology and behaviour. Intriguingly, the gut microbiota of MS offspring differ from that of non-separated offspring, suggesting a mechanistic role for the microbiota-gut-brain axis. Hence, we tested whether dietary factors known to affect the gut microbiota alter the neurobehavioural effects of MS. The impact of consuming diet containing prebiotics polydextrose (PDX) and galactooligosaccharide (GOS) alone or in combination with live bacteria Lactobacillus rhamnosus GG (LGG) from weaning onwards in rats subjected to early-life MS was assessed. Adult offspring were assessed for anxiety-like behaviour in the open field test, spatial memory using the Morris water maze, and reactivity to restraint stress. Brains were examined via PCR for changes in mRNA gene expression. Here, we demonstrate that diets containing a combination of PDX/GOS and LGG attenuates the effects of early-life MS on anxiety-like behaviour and hippocampal-dependent learning with changes to hippocampal mRNA expression of genes related to stress circuitry, anxiety and learning.

The enduring effects of early‐life stress on the microbiota–gut–brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend

“…Notably, this is the first study to show that MFGM consumption results in a significant reduction of the early‐life stress‐induced visceral hypersensitivity. While previous studies have shown that dietary supplementation with probiotics and prebiotics is effective in the reduction of visceral sensitivity (Kannampalli et al., ; McKernan, Fitzgerald, Dinan, & Cryan, ; McVey Neufeld et al., ; Wang et al., ), the impact of MFGM has not been shown before.…”

“…Aspects of central nervous system development such as hippocampal learning are impacted upon by stressors in early‐life (McVey Neufeld et al., ). Here we noted that MFGM alone and combined with the prebiotic blend was sufficient to improve spatial learning in MS rats.…”

“…More recently, this definition has been updated to include non‐carbohydrate substances, applications to body sites other than the gastrointestinal tract and diverse categories other than food (Gibson et al., ). Recently, we (Burokas et al., ; McVey Neufeld et al., ) and others (Mika et al., ; Tarr et al., ; Thompson et al., ; Williams et al., ) have shown that prebiotics can have a positive effect on physiology and behaviour and can reverse the effects of stress and immune activation in adult animals. Moreover, research now shows that a combination of prebiotics and MFGM improves sleep and attenuates the impact of stress in rats (Mika et al., ; Thompson et al., ); however, the ability of MFGM to counter the enduring effects of early‐life stress remains unexplored.…”

Resilience priming: Translational models for understanding resiliency and adaptation to early life adversity

“…L . rhamnosus GG in combination with polydextrose reverses early life stress‐induced effects on anxiety behavior in the open field, learning in the Morris Water Maze & hippocampal GABA receptor mRNA (McVey Neufeld et al, ). Most recently, probiotic administration has been shown to reverse the sex‐dependent ELS‐induced effects of maternal separation on pubertal timing (Cowan & Richardson, ).…”

Microbiota and Neurodevelopmental Trajectories: Role of Maternal and Early-Life Nutrition

“…Maternal separation during early life disrupted the microbiota of the offspring of rhesus monkeys and rats [149, 150]. Interestingly, a diet containing prebiotics in combination with live Lactobacillus rhamnosus GG attenuated the effects of early-life maternal separation on anxiety-like behaviour and hippocampal-dependent learning [151]. Germ-free mice were more vulnerable to restraint stress, resulting in higher adrenocorticotropic hormone and corticosterone in plasma [14, 16], a reduction in glucocorticoid receptor mRNA and an increased stress response [14].…”