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Gut microbiota's effect on mental health: The gut-brain axis.
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Why nurturing the gut microbiota could resolve depression and anxiety.
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Romantic Relationship Dissolution, Microbiota, and Fibers.
Microbiota inhabit nearly every part of our body with the gut microbiota representing the greatest density and absolute abundance. The gut-microbiota-brain axis facilitates bidirectional communication between gut microbiota and the brain. For instance, romantic relationship not only brings joy, it is also associated with increased gut microbiota diversity and health benefits whereas reduced microbiota diversity is related to obesity, cardiac disease, type 2 diabetes, and inflammatory disorders. Research has shown that dietary fibers may increase microbiota diversity and exert antidepressant effect. Among a plethora of life stressors, romantic relationship dissolution is a relatively common and painful experience that people encounter from time to time. Depressed mood, social isolation and poor intake are all associated with romantic relationship dissolution. In this article, it is hypothesized that romantic relationship dissolution is accompanied by decreased gut microbiota diversity which could be corrected with the ingestion of dietary fibers with an additional antidepressant benefit.
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Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy.
Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.
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Development of the Gut Microbiota throughout the First Year of Life and Its Association with Socio-Emotional Development into Childhood.
INTRODUCTION: Early life is a critical window for the development of many bodily systems, including the gut microbiota and the central nervous system, that are interconnected through the gut-brain axis. These early life gut-brain axis connections are often studied through cross-sectional cohorts, limiting insights into temporal developmental trajectories. This longitudinal cohort study assessed whether gut microbial development over the first year of life is associated with socio-emotional development into childhood. METHODS: The PRIDE (pregnancy and infant development) BIOME study (n = 81, n = 42 males) is a focus cohort within the larger prospective PRIDE study. Gut microbiome was measured 5 times throughout the first year of life (at 2, 4, 6, 9, and 12 months through V4 16S rRNA sequencing) and socio-emotional development 8 times over 4.5 years, between 6 months and 5 years through the Ages and Stages Questionnaire: Social-Emotional (ASQ-SE). We related the development of the gut microbiota of infants throughout their first year of life with their socio-emotional development into childhood, the latter modeled as a slope per individual (ASQ slope). We assessed effects of time, ASQ slope and its interaction with time on microbial community measures alpha and beta diversity, as well as taxonomy, using linear mixed-effects models and PERMANOVA, correcting for sex, birth weight, gestational age, and sequencing depth. RESULTS: Expected developmental patterns on the gut microbiota over the first year of life were observed, including increased alpha diversity and clustering of beta diversity before and after solid food introduction. Interestingly, ASQ slope was a significant predictor of beta diversity (F(1,394) = 25.90, p = 0.001) and Bifidobacterium abundance across the first year of life (b = -0.745, SE = 0.24, pFDR = 0.023). Moreover, we observed a temporal association between ASQ slope and Eggerthella abundance (ASQ slope × timepoint interaction, b = 0.709, SE = 0.21, pFDR = 0.009). That is, Eggerthella abundance decreased across the group, but not in "late concern" infants, with concern about socio-emotional development at more recent timepoints. DISCUSSION: This study shows that genera Bifidobacterium and Eggerthella, known to be altered in mental health conditions such as autism spectrum disorder and depression, are already linked to socio-emotional development during early life. Hence, this work contributes to the identification of gut microbial candidates relevant for preventive screening of healthy gut-brain development and microbiota-targeted interventions.
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Ultra-processed food exposure and health outcomes: Current evidence, controversies, and future perspectives.
Ultra-processed food (UPF) exposure has increased markedly worldwide and is now a major contributor to total energy intake in many countries. Evidence from large prospective cohort studies suggests that higher UPF exposure is associated with adverse health outcomes, including overweight and obesity, type 2 diabetes, cardiovascular disease, selected cancers, depression, and increased all-cause mortality. Short-term experimental studies further indicate that diets rich in UPFs can promote excess energy intake and weight gain, supporting biological plausibility. Several mechanisms have been proposed, including poor nutrient quality, high glycemic load, altered food structure and satiety signaling, exposure to additives and contaminants, gut microbiome perturbations, and displacement of minimally processed foods. Nevertheless, the field remains debated. Major controversies concern the Nova classification system, substantial heterogeneity within the UPF category, challenges in reproducible classification, and the extent to which observed associations reflect processing itself rather than nutrient profile, dietary patterns, or broader food environments. These issues hinder causal inference and sustain ongoing debate over whether UPFs act as independent etiological factors or function as markers of unhealthy diets. Policy responses vary internationally, ranging from explicit inclusion of UPFs in dietary guidelines to predominantly nutrient-based or hybrid frameworks. This narrative review summarizes current evidence linking UPF exposure to health outcomes, critically examines methodological and conceptual limitations, and discusses implications for future research and public health policy. See also the graphical abstract(Fig. 1).
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Bulky substrates of isoleucine 2-epimerase: α-Neopentylglycine and NV-5138.
Isoleucine 2-epimerase from Lactobacillus buchneri (LbIleE) catalyzes the pyridoxal 5'-phosphate-dependent, reversible, racemization or epimerization of nonpolar amino acids at the C-2 position. The integral role of the enzyme in the biosynthesis of branched-chain d-amino acids makes it a potential target for the development of antimicrobial agents. Probing the hydrophobic active-site pocket with a series of alkyl boronic acids, we show that the hydrophobic pocket accommodates the neopentyl group with enhanced binding affinity relative to the sec-butyl group. Subsequently, we show that LbIleE catalyzes the racemization of l- and d-α-neopentylglycine, exhibiting binding affinities for these substrates 6- and 24-fold greater than those for l-Ile and d-allo-Ile, but with catalytic efficiencies (kcat/Km) reduced 46- and 27-fold, respectively. NV-5138 is a ligand of the leucine-binding site of Sestrin2, which activates the mechanistic target of rapamycin complex1 (mTORC1) and is structurally similar to α-neopentylglycine. Our demonstration that LbIleE catalyzes the racemization of l-NV-5138 (kcat/Km = 2.2 ± 0.2 s-1 mM-1), along with the fact that L. buchneri can be present in the human gut microbiome, suggests that formation of d-NV-5138 could occur in humans when l-NV-5138 is used as a pharmacological intervention for depression.
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REM sleep behaviour disorder (RBD): Personal perspectives and research priorities.
The formal identification and naming of rapid eye movement (REM) sleep behaviour disorder (RBD) in 1985-1987 is described; the historical background of RBD from 1966 to 1985 is briefly discussed; and RBD milestones are presented. Current knowledge on RBD is identified with reference to recent comprehensive reviews, allowing for a focus on research priorities for RBD: factors and predictors of neurodegenerative phenoconversion from isolated RBD and patient enrolment in neuroprotective trials; isolated RBD clinical research cohorts; epidemiology of RBD; traumatic brain injury, post-traumatic stress disorder, RBD and neurodegeneration; depression, RBD and synucleinopathy; evolution of prodromal RBD to neurodegeneration; gut microbiome dysbiosis and colonic synuclein histopathology in isolated RBD; other alpha-synuclein research in isolated RBD; narcolepsy-RBD; dreams and nightmares in RBD; phasic REM sleep in isolated RBD; RBD, periodic limb movements, periodic limb movement disorder pseudo-RBD; other neurophysiology research in RBD; cardiac scintigraphy (123I-MIBG) in isolated RBD; brain magnetic resonance imaging biomarkers in isolated RBD; microRNAs as biomarkers in isolated RBD; actigraphic, other automated digital monitoring and machine learning research in RBD; prognostic counselling and ethical considerations in isolated RBD; and REM sleep basic science research. RBD research is flourishing, and is strategically situated at an ever-expanding crossroads of clinical (sleep) medicine, neurology, psychiatry and neuroscience.
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The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases.
Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer's disease (AD), Parkinson's Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Presented data shows that consuming a diet abundant in fruits, vegetables, nuts, herbs, spices, and legumes that are sources of anti-inflammatory elements such as omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics while avoiding foods that promote inflammation, create a positive brain environment and is associated with a reduced risk of neurological diseases. Personalized nutritional interventions may constitute a non-invasive and effective strategy in combating neurological disorders.
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Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis.
BACKGROUND: Maternal separation (MS) is an early life stress model that is often studied to determine how early life stress affects brain development and psychopathological adaptation. As society has developed, public health problems have become increasingly prominent, and this research area has attracted significant attention. However, to date, there has been no systematic bibliometric study on MS. The aim of this study was to analyze the trends and frontiers in MS using bibliometrics and provide a scientific reference to researchers in the field. METHODS: Utilizing VOSviewer, CiteSpace, and Microsoft Excel, examined data obtained from the WoSCC, which encompasses the years 2002-2021. RESULTS: In this bibliometric study, we analyzed 6209 articles related to MS authored by 24,174 researchers across 121 countries and regions and published in 2219 journals. The United States had the most publications (2,232, 35.95%) and both the United States and the United Kingdom had the highest h-index. Institutions in the United States and France had the most published articles and citations. Keyword clustering analysis revealed associations between MS and adverse early life experiences, the hypothalamic-pituitary-adrenal (HPA) axis, stress, gene expression, and depression. CONCLUSIONS: This bibliometric analysis highlights the current research focus on the long-term effects of MS on emotional cognition, the HPA axis, epigenetic changes, and their links to gut microbiome imbalances. Future research may expand on these findings to investigate the underlying mechanisms and broader health and societal implications of MS. These results provide a comprehensive overview of the current research landscape in MS and offer valuable insights for researchers to guide future investigations in this field.