Microbe–Immune–Stress Interactions Impact Behaviour during Postnatal Development

Abstract

Decades of research have established the role of microbiota–brain communication in behaviour and brain function. Studies have shown that microbiota composition and diversity are influenced by a variety of factors including host genetics, diet, and other environmental exposures, with implications for the immunological and neurobiological development of the host organism. To further understand early-life interactions between environment, genetic factors, the microbiome and the central nervous system, we investigated the impact of postnatal stress in C57Bl/6 wild type and T-cell deficient mice on microbe–brain interactions and behaviour. Mice were exposed to immune challenge with lipopolysaccharide (LPS) at postnatal day (P) 3 and maternal separation at P9 (16 h overnight). Behavioural assessment of growth and development as well as behaviour (righting reflex, ultrasonic vocalizations in response to brief maternal separation, open field, sociability, and grooming) was conducted. Microbiota diversity and composition of fecal samples collected at P24 revealed reduced alpha diversity in T-cell-deficient mice as well as genotype- and stress-related taxa. Notably, integrated analyses of microbiota and behaviour in the context of immunocompromise revealed key behavioural related taxa that may be important to brain development. These findings are important to determining the influence of genetic and environmental factors on gut microbiota and advances our understanding microbiome–brain signaling pathways on neurodevelopment and behaviour.

Neonatal immune stimulation results in sex‐specific changes in ultrasonic vocalizations but does not affect seizure susceptibility in neonatal mice

“…However, not many studies have evaluated the consequences of neonatal immune activation in the USVs paradigm. The few studies that have investigated these effects during the neonatal period induced the immune stimulus earlier in development, from PD3 to PD9, while in the present study, we administrated LPS at PD10 (Carlezon et al, 2019; Francella et al, 2022; Pang et al, 2016). Carlezon and colleagues showed a dimorphic response in vocalization number and duration in response to neonatal LPS administration (Carlezon et al, 2019).…”

“…Several animal models of ASD and epilepsy have been shown to exhibit altered communication using this paradigm (Gzielo et al, 2020; Huebschman et al, 2020; Nguyen et al, 2023; Scattoni et al, 2008; Shekel et al, 2021). The acute effects of neonatal inflammation on communication, however, have not been extensively investigated (Carlezon et al, 2019; Francella et al, 2022; Pang et al, 2016).…”

Industrial and Ruminant Trans-Fatty Acids-Enriched Diets Differentially Modulate the Microbiome and Fecal Metabolites in C57BL/6 Mice

“…Prior to differential abundance analysis, ASV tables were further preprocessed using the retain resolve method, as previously described [ 26 ]. In brief, taxa were sequentially filtered and glommed to obtain a final dataset that retains biologically significant taxonomic classifications while removing noise in the form of spurious sequences and highly partitioned subgroups.…”

The gut microbiota-immune-brain axis in a wild vertebrate: dynamic interactions and health impacts

“…However, several parts of the feedback cascade appeared to be functional (see below). Despite the well-established influence of the gut microbiota on immune system modulation and its impact on the CNS, these tripartite connections remain elusive in wild populations (Hird, 2017;Davidson et al, 2020;Madden et al, 2022;Pereira et al, 2023), particularly during the early stages of development, in contrast to the studies in humans and mice (Martin et al, 2018;Francella et al, 2022;Lynch et al, 2024).…”

“…In murine models, penicillin treatment during late pregnancy and early postnatal life has been shown to induce alterations in the gut microbiota, leading to heightened cytokine expression, altered integrity of the blood-brain barrier, and significant differences in behaviour (Ratsika et al, 2023). Interactions among these functional systems, particularly during sensitive developmental periods, carry consequences later in life, influencing behaviour, disease susceptibility, general health and survival (Strange et al, 2016;Francella et al, 2022;Ratsika et al, 2023). Substantial evidence emphasises the importance of the microbiota-immune-brain axis in humans and laboratory animals (Fung, 2020).…”