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•Perception learning causes a transient increase in brain grey matter volume detectable by MRI.•This learning results in pronounced changes of neuronal dendrites and an increase in the number of dendritic spines.•Structural neuronal plasticity is associated with a reorganization and transient swelling of astrocytes.•Brain volume and astrocyte volume return to baseline post-learning, with a persistent increase in the number of mature spines. Volumetric magnetic resonance imaging studies have shown that intense learning can be associated with grey matter volume increases in the adult brain. The underlying mechanisms are poorly understood. Here we used monocular deprivation in rats to analyze the mechanisms underlying use-dependent grey matter increases. Optometry for quantification of visual acuity was combined with volumetric magnetic resonance imaging and microscopic techniques in longitudinal and cross-sectional studies. We found an increased spatial vision of the open eye which was associated with a transient increase in the volumes of the contralateral visual and lateral entorhinal cortex. In these brain areas dendrites of neurons elongated, and there was a strong increase in the number of spines, the targets of synapses, which was followed by spine maturation and partial pruning. Astrocytes displayed a transient pronounced swelling and underwent a reorganization of their processes. The use-dependent increase in grey matter corresponded predominantly to the swelling of the astrocytes. Experience-dependent increase in brain grey matter volume indicates a gain of structure plasticity with both synaptic and astrocyte remodeling.

Perinatal mood disorders, including depression and anxiety, are common. Pregnant and lactating women often limit their use of medications, thus a safe and natural solution to improve mood would be welcomed. There is increasing evidence that probiotics such as Bifidobacterium longum NCC3001 can influence mental well-being of adults; however, their impact on mental health during pregnancy and after birth remains unknown. The current double-blind, placebo-controlled, randomized, 3-parallel-arm study ( N  = 184) evaluated the efficacy of orally consumed B. longum (BL) NCC3001 either during pregnancy and postpartum (from approximately 30 weeks’ gestation until 12 weeks after delivery) or postpartum only (from birth until 12 weeks after delivery) compared to a placebo control group in reducing depressive and anxiety symptoms assessed by EPDS and STAI self-administered questionnaires in late pregnancy and across 12 weeks postpartum. Contrary to our hypothesis, we did not observe any differences between groups in mood outcomes. Mood scores showed large variability among participants, as well as notable fluctuations within individuals over the course of the study. Additionally, it should be noted that BL NCC3001 was not detected after the intervention in all of the intervention group participants. More research is needed to understand the underpinnings of perinatal mood disturbances and microbial changes, and whether probiotics could improve mood during this period.

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. 6EAm88ZArXmof6xJwC_DMV Video abstract.

Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age.

Psychological stress during adolescence may cause enduring cognitive deficits and anxiety in both humans and animals, accompanied by rearrangement of numerous brain structures and functions. A healthy diet is essential for proper brain development and maintenance of optimal cognitive functions during adulthood. Furthermore, nutritional components profoundly affect the intestinal community of microbes that may affect gut-brain communication. We adopted a relatively mild stress protocol, social instability stress, which when repeatedly administered to juvenile rats modifies cognitive behaviors and plasticity markers in the brain. We then tested the preventive effect of a prolonged diet enriched with the ω-3 polyunsaturated fatty acids eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid and vitamin A. Our findings highlight the beneficial effects of this enriched diet on cognitive memory impairment induced by social instability stress, as stressed rats fed the enriched diet exhibited performance undistinguishable from that of nonstressed rats on both emotional and reference memory tests. Furthermore, in stressed rats, the decline in brain-derived neurotrophic factor expression in the hippocampus and shifts in the microbiota composition were normalized by the enriched diet. The detrimental behavioral and neurochemical effects of adolescent stress, as well as the protective effect of the enriched diet, were maintained throughout adulthood, long after the exposure to the stressful environment was terminated. Taken together, our results strongly suggest a beneficial role of nutritional components in ameliorating stress-related behaviors and associated neurochemical and microbiota changes, opening possible new venues in the field of nutritional neuropsychopharmacology.

Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6Chi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C+) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.

Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.

The gut microbiota plays crucial roles in maintaining the health and homeostasis of its host throughout lifespan, including through its ability to impact brain function and regulate behaviour during ageing. Studies have shown that there are disparate rates of biologic ageing despite equivalencies in chronologic age, including in the development of neurodegenerative diseases, which suggests that environmental factors may play an important role in determining health outcomes in ageing. Recent evidence demonstrates that the gut microbiota may be a potential novel target to ameliorate symptoms of brain ageing and promote healthy cognition. This review highlights the current knowledge around the relationships between the gut microbiota and host brain ageing, including potential contributions to age-related neurodegenerative diseases. Furthermore, we assess key areas for which gut microbiota-based strategies may present as opportunities for intervention.

Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 10[sup.10] CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.