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Abstract Background The gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes. Methods Stool samples were collected from a community sample of 248 typically developing children (3–5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated. Results Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner. Conclusions These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract

The COVID-19 pandemic was a substantial stressor, especially for pregnant individuals. We aimed to understand the impact of COVID-19-related stresses on pregnant individuals and their infants and collected survey-based data across Canada as part of the Pregnancy during the COVID-19 Pandemic (PdP) project. The dataset described here provides baseline prenatal data and basic birth outcomes from PdP participants. This data includes information from pregnant individuals as well as their infants.At enrolment and time of completion of the baseline survey, participants were pregnant, ≥17 years of age, ≤35 weeks of gestation, living in Canada, and able to read and write in English or French. Baseline data were collected between April 2020-April 2021. Infant data were collected between May 2020-December 2021. All data were collected via self-report using online questionnaires in REDCAP. Questionnaires were available in both English and French. Data were checked for completeness and plausibility, and duplicates were removed.The dataset described here includes age, education, and household income of the pregnant individuals reported at the baseline/enrollment survey. Raw scores are provided for the Edinburgh Postnatal Depression Scale (EPDS) and the PROMIS Anxiety scale. Ratings are also given for three variables describing fear of the COVID-19 virus.Birth outcomes are provided for infants, including gestational age at birth, birthweight, length, mode of delivery, and whether the infant spent time in the neonatal intensive care unit (NICU). Delivery date is reported as month and year.These data will be beneficial for anyone interested in researching stress during pregnancy or birth outcomes in the context of the COVID-19 pandemic. They will also be useful to researchers interested in examining more general effects of prenatal distress on birth outcomes in children. Data could also be compared to other datasets from the COVID-19 pandemic to establish generalizability, or to pre-pandemic datasets to determine the extent of changes during the COVID-19 pandemic.

Scientific advancements in understanding the impact of bioactive components in foods on the gut microbiota and wider physiology create opportunities for designing targeted functional foods. The selection of bioactive ingredients with potential local or systemic effects holds promise for influencing overall well-being. An abundance of studies demonstrate that gut microbiota show compositional changes that correlate age and disease. However, navigating this field, especially for non-experts, remains challenging, given the abundance of bioactive ingredients with varying levels of scientific substantiation. This narrative review addresses the current knowledge on the potential impact of the gut microbiota on host health, emphasizing gut microbiota resilience. It explores evidence related to the extensive gut health benefits of popular dietary components and bioactive ingredients, such as phytochemicals, fermented greens, fibres, prebiotics, probiotics, and postbiotics. Importantly, this review distinguishes between the potential local and systemic effects of both popular and emerging ingredients. Additionally, it highlights how dietary hormesis promotes gut microbiota resilience, fostering better adaptation to stress—a hallmark of health. By integrating examples of bioactives, this review provides insights to guide the design of evidence-based functional foods aimed at priming the gut for resilience.

IntroductionDietary changes are common in pregnancy and may affect pregnancy outcomes, yet these changes and the associated contributory factors during the COVID-19 pandemic have been understudied. We aimed to investigate the association between dietary change and socioeconomic variables, pre-pregnancy BMI, and mental health symptoms; the change in intake of seven food categories and their reasons; and the association between intake of these food categories and mental health symptoms.Materials and methodsIn this cross-sectional analysis, we used data from the Pregnancy during the COVID-19 Pandemic (PdP) cohort study that collected data from pregnant Canadian individuals (n = 9,870, gestational age ≤ 35 weeks) on socioeconomic factors, pandemic-related hardships, pre-pregnancy body mass index (BMI), dietary changes compared to pre-pandemic and the reasons for these changes. We assessed depressive and anxiety symptoms using the Edinburgh Postpartum Depression Scale (EPDS) and Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety, respectively.Results54.3% of the participants reported a change in their diet. Non-white ethnicity (OR = 1.33), job loss (OR = 1.29), clinically elevated depressive and anxiety symptoms (OR = 1.26 and 1.14, respectively), self-isolation (OR = 1.20), pre-pregnancy BMI (OR = 1.19), fear of COVID-19 (OR = 1.15), and pandemic phase at enrolment (OR = 0.90) significantly predicted dietary change. Most participants ate about the same amounts of dairy, meats and canned foods/dried goods as pre-pandemic (61.5, 61.7, and 60.2%, respectively), increased their intake of fresh vegetables/fruits and sweets/snacks (43.2 and 54.5%, respectively), and decreased fast-food and take-out/home delivery (53.2 and 43.1%, respectively). Changes in consumption of the food categories had a curvilinear association with mental health symptoms (except resilience) indicating greater symptoms with either decreased or increased intakes. Changes in craving, having more time for cooking/preparing foods, and being unable to go grocery shopping frequently (but not reduced affordability) were the main reasons driving these dietary changes.ConclusionSome factors increase the odds of dietary change among pregnant individuals during the pandemic, with some changes toward a healthy and others toward an unhealthy diet. Given the importance of a healthy diet during gestation, identifying the risk and protective factors might be the first essential step in reducing the detrimental effects of unfavorable dietary changes during the pandemic on this vulnerable population.

Aging has a significant impact on physiology with implications for central nervous system function coincident with increased vulnerability to stress exposures. A number of stress-sensitive molecular mechanisms are hypothesized to underpin age-related changes in brain function. Recent cumulative evidence also suggests that aging impacts gut microbiota composition. However, the impact of such effects on the ability of mammals to respond to stress in aging is still relatively unexplored. Therefore, in this study we assessed the ability of a microbiota-targeted intervention (the prebiotic FOS-Inulin) to alleviate age-related responses to stress. Exposure of aged C57BL/6 mice to social defeat led to an altered social interaction phenotype in the social interaction test, which was reversed by FOS-Inulin supplementation. Interestingly, this occured independent of affecting social defeat-induced elevations in the stress hormone corticosterone. Additionally, the behavioral modifications following FOS-Inulin supplementation were also not coincident with improvement of pro-inflammatory markers. Metabolomics analysis was performed and intriguingly, age associated metabolites were shown to be reduced in the prefrontal cortex of stressed aged mice and this deficit was recovered by FOS-Inulin supplementation. Taken together these results suggest that prebiotic dietary intervention rescued the behavioral response to stress in aged mice, not through amelioration of the inflammatory response, but by restoring the levels of key metabolites in the prefrontal cortex of aged animals. Therefore, dietary interventions could be a compelling avenue to improve the molecular and behavioral manifestations of chronic stress exposures in aging via targeting the microbiota-gut brain axis.

Abstract Background Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. Video abstract.

Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.