The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 h, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which through metabolic, cellular, and circadian mechanisms lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease, and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischemic stroke, autism spectrum disorder, and mood and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Moreover, variations in fasting patterns, total caloric intake, and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and randomized clinical trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (N_ADHD = 42; N_controls = 50; N_{subthreholdADHD} = 15; range age: 13–29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Alpha and Beta-diversity were not different between participants with ADHD and healthy controls. Three genera showed nominal differences (p_uncorrected < 0.05) between both groups (Prevotella_9, Coprococcus_2 and Intestinibacter) and were further tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, a time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that the variation of a genus from the Lachnospiraceae family (Coprococcus_2) showed a trend of being negatively associated with inattention symptoms. Furthermore, we showed that the relative abundance of four genera was reduced by ADHD medication (p_uncorrected < 0.05). Overall, our results may support the role of the gut microbiota in the pathophysiology of ADHD. Given the scarcity of studies on the gut microbiota in individuals with ADHD, the current results are an important contribution to this field. More studies are needed into the gut microbiota as part of the pathology of ADHD, especially with a bigger sample size across the lifespan and more detailed information about lifestyle.

Stress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, in exploratory analyses, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli, Lactococci, and Bifidobacteria in healthy, female subjects (probiotics group n = 27, placebo group n = 29). In an identical pre-session and post-session, subjects performed a working memory task before and after an acute stress intervention. Global gut microbial beta diversity changed over time, but we were not able to detect differences between intervention groups. At the taxonomic level, Time by Intervention interactions were not significant after multiple comparison correction; the relative abundance of eight genera in the probiotics group was higher (uncorrected) relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005, and Ruminococcaceae_UCG-010. In a second analysis step, association analyses were done only within this selection of microbial genera, revealing the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics’ effect on stress-induced working memory changes (r_spearman(27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fiber intake). That is subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fiber degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g., maintaining intestinal-barrier and blood–brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.

A body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. Linking measures of brain connectivity to the gut microbiota can provide important mechanistic insights into the bi-directional gut-brain communication. In this systematic review, we therefore synthesized the available literature assessing this association, evaluating the degree of consistency in microbiota-connectivity associations. Following the PRISMA guidelines, a PubMed search was conducted, including studies published up to September 1, 2022. We identified 16 studies that met the inclusion criteria. Several bacterial genera, including Prevotella, Bacteroides, Ruminococcus, Blautia, and Collinsella were most frequently reported in association with brain connectivity. Additionally, connectivity of the salience (specifically the insula and anterior cingulate cortex), default mode, and frontoparietal networks were most frequently associated with the gut microbiota, both in terms of microbial diversity and composition. There was no discernible pattern in the association between microbiota and brain connectivity. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, many findings were poorly replicated across studies, and the specificity of the association is yet unclear. The current studies show substantial inter-study heterogeneity in methodology and reporting, limiting the robustness and reproducibility of the findings and emphasizing the need to harmonize methodological approaches. To enhance comparability and replicability, future research should focus on further standardizing processing pipelines and employing data-driven multivariate analysis strategies.

The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning. In healthy older adults, impairments have been demonstrated in two forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing) under high information load. However, no study has directly compared the effects of a catecholamine precursor on reactive and load-dependent proactive inhibition. In this study we explored the effects of tyrosine on reactive and proactive response inhibition and signal in dopaminergically innervated fronto-striatal regions. Depending on age, tyrosine might lead to beneficial or detrimental neurocognitive effects. We aimed to address these hypotheses in 24 healthy older human adults (aged 61–72 years) using fMRI in a double blind, counterbalanced, placebo-controlled, within-subject design. Across the group, tyrosine did not alter reactive or proactive inhibition behaviorally but did increase fronto-parietal proactive inhibition-related activation. When taking age into account, tyrosine affected proactive inhibition both behaviorally and neurally. Specifically, increasing age was associated with a greater detrimental effect of tyrosine compared with placebo on proactive slowing. Moreover, with increasing age, tyrosine decreased fronto-striatal and parietal proactive signal, which correlated positively with tyrosine’s effects on proactive slowing. Concluding, tyrosine negatively affected proactive response slowing and associated fronto-striatal activation in an age-dependent manner, highlighting the importance of catecholamines, perhaps particularly dopamine, for proactive response inhibition in older adults.