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.
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.
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
(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.
Scope
To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non‐MedDiet exerts a greater beneficial effect on gut microbiota and fecal ...metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors.
Methods and Results
Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2‐months dietary‐intervention trial with a 1‐month wash‐out period, following a MedDiet or consuming nuts (50 g day‐1). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC‐qTOF) platforms in a targeted metabolomics approach.
Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA‐IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA‐IR, while positively and negatively with changes in cholate and cadaverine, respectively.
Conclusions
Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.
Following a Mediterranean diet (MedDiet) rather than a regular diet supplemented with nuts increases the abundance of Lachnospiraceae NK4A136 which is associated with MedDiet benefits on insulin metabolism, partially explained by fecal cholate increases and cadaverine decreases.
The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, ...however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery.
Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test.
Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals' behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders. Video abstract.
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
= 42; N
= 50; N
= 15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (
< 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use, and family relatedness). Our results show that variation of a genus from the
family (
) is associated (after multiple testing correction) with inattention symptoms and support the potential role of gut microbiota in ADHD pathophysiology.
Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This ...review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets’ effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome–gut–brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet’s efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.
•The gut microbiota link to the Research Domains Criteria functional domains.•The associations span across neurodevelopmental and stress-related disorders.•There is a mix of domain-specific and ...psychiatry-general microbiota associations.•A dimensional approach clarifies the specificity of the gut-brain relationship.•The identified genera suggest involvement of immune-related processes.
Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity.
The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status.
Four functional domains, aligning with RDoC’s negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all pFDR < 0.05).
Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways.
The left and right sides of the human brain are specialized for different kinds of information processing, and much of our cognition is lateralized to an extent toward one side or the other. ...Handedness is a reflection of nervous system lateralization. Roughly ten percent of people are mixed- or left-handed, and they show an elevated rate of reductions or reversals of some cerebral functional asymmetries compared to right-handers. Brain anatomical correlates of left-handedness have also been suggested. However, the relationships of left-handedness to brain structure and function remain far from clear. We carried out a comprehensive analysis of cortical surface area differences between 106 left-handed subjects and 1960 right-handed subjects, measured using an automated method of regional parcellation (FreeSurfer, Destrieux atlas). This is the largest study sample that has so far been used in relation to this issue. No individual cortical region showed an association with left-handedness that survived statistical correction for multiple testing, although there was a nominally significant association with the surface area of a previously implicated region: the left precentral sulcus. Identifying brain structural correlates of handedness may prove useful for genetic studies of cerebral asymmetries, as well as providing new avenues for the study of relations between handedness, cerebral lateralization and cognition.
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