Intracerebral hemorrhage is the most dangerous subtype of stroke, characterized by high mortality and morbidity rates, and frequently leads to significant secondary white matter injury. In recent decades, studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota-brain axis. This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury. The NACHT, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in this context. This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome. These mechanisms include metabolic pathways (involving short-chain fatty acids, lipopolysaccharides, lactic acid, bile acids, trimethylamine-N-oxide, and tryptophan), neural pathways (such as the vagus nerve and sympathetic nerve), and immune pathways (involving microglia and T cells). We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage. The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood-brain barrier, inducing neuroinflammation, and interfering with nerve regeneration. Finally, we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury. Our review highlights the critical role of the gut microbiota-brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage, paving the way for exploring potential therapeutic approaches.

The establishment and maintenance of immune homeostasis rely on a dynamic, bidirectional exchange of information between commensal microorganisms and the host immune system. At the center of this process are CD4+Foxp3+ regulatory T cells (Tregs), which have emerged as pivotal mediators to ensure immunological equilibrium. This review explores the sophisticated mechanisms by which the gut microbiota modulates the differentiation, expansion, and functional specialization of Tregs, orchestrating intestinal immune tolerance to support host-microbiota mutualism. We discuss the role of microbial-derived structural components and metabolites in shaping the immunoregulatory fitness of Tregs. Additionally, we explore the impact of gut microbial dysbiosis, where disrupted microbial-immune crosstalk compromises immune tolerance, contributing to the development of inflammatory and autoimmune disorders. Finally, we highlight the potential of microbiota-based strategies to recalibrate intestinal immunity and restore immune tolerance.

The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.

Exposure to stress during sensitive developmental periods comes with long term consequences for neurobehavioral outcomes and increases vulnerability to psychopathology later in life. While we have advanced our understanding of the mechanisms underlying the programming effects of early-life stress (ES), these are not yet fully understood and often hard to target, making the development of effective interventions challenging. In recent years, we and others have suggested that nutrition might be instrumental in modulating and possibly combatting the ES-induced increased risk to psychopathologies and neurobehavioral impairments. Nutritional strategies are very promising as they might be relatively safe, cheap and easy to implement. Here, we set out to comprehensively review the existing literature on nutritional interventions aimed at counteracting the effects of ES on neurobehavioral outcomes in preclinical and clinical settings. We identified eighty six rodent and ten human studies investigating a nutritional intervention to ameliorate ES-induced impairments. The human evidence to date, is too few and heterogeneous in terms of interventions, thus not allowing hard conclusions, however the preclinical studies, despite their heterogeneity in terms of designs, interventions used, and outcomes measured, showed nutritional interventions to be promising in combatting ES-induced impairments. Furthermore, we discuss the possible mechanisms involved in the beneficial effects of nutrition on the brain after ES, including neuroinflammation, oxidative stress, hypothalamus-pituitary-adrenal axis regulation and the microbiome-gut-brain axis. Lastly, we highlight the critical gaps in our current knowledge and make recommendations for future research to move the field forward.

The etiology of mood and schizophrenia spectrum disorders remains largely unknown. In recent years, several studies have focused on the role of the microbiome-gut-brain-axis (MGBA) in its etiology, providing several novel insights. The communication within MGBA involves various pathways leading through the vagus nerve and the bloodstream mediators. The latter are represented by short-chain fatty acids (SCFAs), produced by gut microbiota from dietary fiber. To date, several physiological and pathophysiological roles in the periphery and the central nervous system for SCFAs have been suggested. Studies investigating gut microbiota have consistently reported a decreased abundance of bacteria-producing SCFAs in people with mood and schizophrenia spectrum disorders. Yet, studies investigating faecal and blood levels of SCFAs have provided mixed findings. The present article provides a narrative review of studies examining the physiological roles of SCFAs, along with animal model and human studies addressing the involvement of SCFAs in mood and schizophrenia spectrum disorders, formulates future directions and provides translational perspectives.

Research over the past two decades has established a remarkable ability of the gut microbiota to modulate brain activity and behaviour. Conversely, signals from the brain can influence the composition and function of the gut microbiota. This bidirectional communication across the gut microbiota-brain axis, involving multiple biochemical and cellular mediators, is recognized as a major brain-body network that integrates cues from the environment and the body's internal state. Central to this network is the gut sensory system, formed by intimate connections between chemosensory epithelial cells and sensory nerve fibres, that conveys interoceptive signals to the central nervous system. In this Review, we provide a broad overview of the pathways that connect the gut and the brain, and explore the complex dialogue between microorganisms and neurons at this emerging intestinal neuroepithelial interface. We highlight relevant microbial factors, endocrine cells and neural mechanisms that govern gut microbiota-brain interactions and their implications for gastrointestinal and neuropsychiatric health.

To investigate the role of intestinal flora and cholinergic anti-inflammatory pathways in the gut-brain axis, using oral gavage and intraperitoneal injection of methyllycaconitine (MLA). MLA was administered at a dose of 4 mg/kg for 30 days, either orally or via intraperitoneal injection. Rats were then assessed for behavioral changes, inflammatory markers, neurotransmitters, neuroreceptors, and intestinal mucosal barrier integrity. Rats receiving MLA via intraperitoneal injection exhibited significant behavioral abnormalities compared to the control and orally administered MLA groups. The levels of IL-1β were elevated in both intestinal and hippocampal tissues, while IL-10 levels were decreased. Brain-derived neurotrophic factor (BDNF) was significantly lower in hippocampal tissues. Furthermore, α7nAChR expression was reduced in hippocampal tissues, accompanied by an increase in 5-HT3A receptors. The intestinal mucosal barrier was compromised, as evidenced by reduced expression of ZO-1 and Occludin, along with increased IL-1β and decreased IL-10 levels in the gut. Our findings suggest that oral gavage of MLA does not induce cognitive impairment in rats compared to intraperitoneal injection, possibly due to the involvement of intestinal flora in the protective effects of CAP.

Objectives: Constipation is one of the most prevalent gastrointestinal disorders worldwide. Recent studies have demonstrated that probiotics may alleviate constipation by restoring gut microbiota balance. Methods: This study investigated the effects of Weizmannia coagulans BC99 (formerly Bacillus coagulans BC99) on gut microbiota and intestinal function in a loperamide-induced mouse model of functional constipation. BALB/c mice were randomly divided into six groups: control, model, phenolphthalein, BC99-L (2 × 107 CFU/day), BC99-M (2 × 108 CFU/day), and BC99-H (2 × 109 CFU/day). After 14 days of supplementation, constipation was induced in mice via loperamide administration. Results: BC99 significantly increased fecal water content, gastrointestinal transit rate, microbial metabolic activity, and butyric acid production, while decreasing the abundance of inflammation-related metabolic pathways. Moreover, BC99 improved levels of gastrointestinal regulatory peptides, including motilin and somatostatin. The Firmicutes-to-Bacteroidetes ratio was elevated in the BC99-M and the BC99-H group compared to the model group, indicating that BC99 effectively modulated gut microbiota composition and host biosynthetic pathways. Conclusions:Weizmannia coagulans BC99 alleviated and prevented loperamide-induced functional constipation in mice by enhancing intestinal peristalsis and restoring gut microbial homeostasis.

Convergent data across species paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function, mediating most neuronal inhibition. Until recently, GABA's role and specific molecular targets in the periphery within the BGM axis had received limited attention. Yet, GABA is produced by neuronal and non-neuronal elements of the BGM, and recently, GABA-modulating bacteria have been identified as key players in GABAergic gut systems, indicating that GABA-mediated signalling is likely to transcend physiological boundaries and species. We review the available evidence to better understand how GABA facilitates the integration of molecularly and functionally disparate systems to bring about overall homeostasis and how GABA perturbations within the BGM axis can give rise to multi-system medical disorders, thereby magnifying the disease burden and the challenges for patient care. Analysis of transcriptomic databases revealed significant overlaps between GABAAR subunits expressed in the human brain and gut. However, in the gut, there are notable expression profiles for a select number of subunits that have received limited attention to date but could be functionally relevant for BGM axis homeostasis. GABAergic signalling, via different receptor subtypes, directly regulates BGM homeostasis by modulating the excitability of neurons within brain centres responsible for gastrointestinal (GI) function in a sex-dependent manner, potentially revealing mechanisms underlying the greater prevalence of GI disturbances in females. Apart from such top-down regulation of the BGM axis, a diverse group of cell types, including enteric neurons, glia, enteroendocrine cells, immune cells and bacteria, integrate peripheral GABA signals to influence brain functions and potentially contribute to brain disorders. We propose several priorities for this field, including the exploitation of available technologies to functionally dissect components of these GABA pathways within the BGM, with a focus on GI and brain-behaviour-disease. Furthermore, in silico ligand-receptor docking analyses using relevant bacterial metabolomic datasets, coupled with advances in knowledge of GABAAR 3D structures, could uncover new ligands with novel therapeutic potential. Finally, targeted design of dietary interventions is imperative to advancing their therapeutic potential to support GABA homeostasis across the BGM axis.

Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease caused by the decrease in estrogen levels after menopause. It leads to bone loss, microstructural damage, and an increased risk of fractures. Studies have found that the gut microbiota and its metabolites can regulate bone metabolism through the gut-bone axis and the gut-brain axis. As research progresses, PMOP has been found to be associated with gut microbiota dysbiosis and Th17/Treg imbalance. The gut microbiota is closely related to the development and differentiation of Treg and Th17 cells. Among them, the metabolites of the gut microbiota such as short-chain fatty acids (SCFAs) can regulate the differentiation of effector T cells by acting on molecular receptors on immune cells, thereby regulating the bone immune process. The multifaceted relationship among the gut microbiota, SCFAs, Th17/Treg cell-mediated bone immunity, and bone metabolism is eliciting attention from researchers. Through a review of existing literature, we have comprehensively summarized the effects of the gut microbiota and SCFAs on PMOP, especially from the perspective of Th17/Treg balance. Regulating this balance may provide new opportunities for PMOP treatment.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

The gut microbiota is amenable to early nutrition including micronutrients but intake above and below the recommendations commonly occur with unknown consequences. Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine found centrally and peripherally with diverse functions such as food intake regulation via the hypothalamic 5-HT receptor 2C (5-HTR2C). This study determined the impact of prenatal micronutrients on the gut microbiota and serotonergic system in offspring. Pregnant Wistar rats were fed either recommended vitamins (RV), high vitamins (HV), high folic acid with recommended choline (HFRC), or high folic acid with no choline (HFNC). Offspring were fed a high-fat diet for 12 weeks postweaning. HV, HFRC, and HFNC males and females had lower hypothalamic 5-HTR2C protein expression compared to RV. Brain 5-HT concentrations were lower but colon 5-HT concentrations were higher in HV and HFNC males and females and HFRC males compared to RV. Refeeding response after 5-HTR2C agonist was negatively correlated with hypothalamic 5-HTR2C protein expression in males and with brain 5-HT concentrations in females. Random forest revealed top bacterial taxa, which Lactococcus, Ruminococcus, Bacteroides, and Oscillospira showed significant correlations with refeeding response and concentrations of brain and colon 5-HT. In conclusion, excess or imbalanced prenatal consumption of micronutrients leads to gut microbiota-associated disturbances in the serotonergic system in offspring.

Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.

The gut-brain axis (GBA) is a bidirectional communication network between the gastrointestinal tract and the brain, modulated by gut microbiota and related biomarkers. Malnutrition disrupts GBA homeostasis, exacerbating GBA dysfunction through gut dysbiosis, impaired neuroactive metabolite production, and systemic inflammation. Nutraceuticals, including probiotics, prebiotics, synbiotics, postbiotics, and paraprobiotics, offer a promising approach to improving GBA homeostasis by modulating the gut microbiota composition and related neuroactive metabolites. This review aims to elucidate the interplay between gut microbiota-derived biomarkers and GBA dysfunction in malnutrition and evaluate the potential of nutraceuticals in combating malnutrition. Furthermore, it explores the future of personalised nutraceutical interventions tailored to individual genetic and microbiome profiles, providing a targeted approach to optimise health outcomes. The integration of nutraceuticals into GBA health management could transform malnutrition treatment and improve cognitive and metabolic health.

Tryptophan (Trp) is an important essential amino acid that plays a variety of physiological functions in the human body, including being a precursor of neurotransmitter and participating in immune regulation. Currently, more and more studies show that some pollutants in the environment can affect the metabolism of Trp and consequently affect human health. The present paper offers a comprehensive overview of prior research investigating the impact of environmental pollutants, including inorganic and organic contaminants, microplastics, and nanoplastics on the nervous system, immune system, digestive system, and maternal-fetal pregnancy, revealing their detrimental effects on Trp metabolism and human well-being.

Kynurenic acid (KYNA) is one of the metabolites of tryptophan (Trp), which can be supplied by endogenous synthesis or diet and involves various aspects of nutrition and metabolism. KYNA has been proven to be an antagonist of α7-nicotinic acetylcholine and NMDA receptors, which can regulate the neurotransmission of cholinergic and glutaminergic acid, so KYNA is mainly associated with neurodegenerative diseases. Other metabolites in the Trp and kynurenine metabolic pathways, such as 3-hydroxy-l-kynurenine (3-HK), 5-hydroxytryptophan (5-HT), and quinolinic acid (QA), are also involved in immune regulation and have pro-stimulatory or anti-excitatory toxicity. KYNA is present in both the human body and the daily diet, so it has the potential as a new dietary supplement. It may be of great significance in treating psychiatric disorders.

Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, with emerging research suggesting a critical link between intestinal dysbiosis and PD progression. This review explores the pathophysiological mechanisms underlying PD, such as alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, while focusing on the impact of gut dysbiosis on intestinal barrier function and its role in reduced neurochemical production. The clinical features of PD, including dopamine, serotonin, and GABA deficiencies, are examined, with a focus on how dysbiosis contributes to neurotransmitter depletion. Current treatments of PD, such as levodopa and dopamine agonists, are discussed alongside gut health therapies such as probiotics, prebiotics, and Fecal Microbiota Transplantation (FMT). Future therapeutic directions, including synbiotics, engineered microbes, phage therapy, and the integration of machine learning (ML) and artificial intelligence (AI), are explored. The chapter also considers preventive strategies, such as lifestyle adjustments and early gut health monitoring using modern diagnostic tools and biosensors. Furthermore, a strong need for continued research into the gut-brain axis (GBA) to develop more effective, gut-targeted therapies for managing PD is discussed.

Perioperative neurocognitive disorders (PND) refer to a constellation of symptoms that primarily affect the elderly and typically manifest as common complications after exposure to surgery and anesthesia. PND is associated with high morbidity, mortality, and progression to neurodegenerative diseases, thus exerting significant financial strains on families as well as the healthcare system. Given that an ageing global population is an inevitable trend and, with the latest advances in the healthcare system, an ever-growing number of elderly people present for surgery and anesthesia, PND is of prominent concern. The two-way communication between the intestinal flora and the brain, also known as the microbiota-gut-brain axis, plays an important role in central nervous system development, and multiple studies have highlighted the influence exerted by gut microbiome in both health and disease. Pertinent studies have corroborated the fact that anesthesia and surgery disrupt the harmony of the gut ecology, which sets off a cascade of events that initiate neuroinflammation, eventually leading to PND. Probiotics, which are live microorganisms that promote the host's health, have been shown as a viable option to restore or minimise the disruption of gut flora. Evidence exists that probiotics exhibit immunomodulatory and anti-inflammatory benefits. Given the effectiveness of probiotics in reducing neuroinflammation, research has also focused on their impact on the development of PND. This review aims to compile the data from relevant clinical trials focusing on the influence of probiotics on PND to determine whether the derived findings might be applied for the prevention and treatment of PND.

Serotonin is one of the most potent gastrointestinal, peripheral, and neuronal signaling molecules and plays a key role in regulating energy metabolism. Accumulating evidence has shown the complex interplay between gut microbiota and host energy metabolism. In this review, we summarize recent findings on the role of gut microbiota in serotonin metabolism and discuss the complicated mechanisms by which serotonin, working in conjunction with the gut microbiota, affects total body energy metabolism in the host. Gut microbiota affects serotonin synthesis, storage, release, transport, and catabolism. In addition, serotonin plays an indispensable role in regulating host energy homeostasis through organ crosstalk and microbe-host communication, particularly with a wide array of serotonergic effects mediated by diverse serotonin receptors with unique tissue specificity. This fresh perspective will help broaden the understanding of serotonergic signaling in modulating energy metabolism, thus shedding light on the design of innovative serotonin-targeting strategies to treat metabolic diseases.

The crypt-villus structure of the small intestine serves as an essential protective barrier. The integrity of this barrier is monitored by the complex sensory system of the gut, in which serotonergic enterochromaffin (EC) cells play an important part1,2. These rare sensory epithelial cells surveil the mucosal environment for luminal stimuli and transmit signals both within and outside the gut3-6. However, whether EC cells in crypts and villi detect different stimuli or produce distinct physiological responses is unknown. Here we address these questions by developing a reporter mouse model to quantitatively measure the release and propagation of serotonin from EC cells in live intestines. Crypt EC cells exhibit a tonic low-level mode that activates epithelial serotonin 5-HT4 receptors to modulate basal ion secretion and a stimulus-induced high-level mode that activates 5-HT3 receptors on sensory nerve fibres. Both these modes can be initiated by the irritant receptor TRPA1, which is confined to crypt EC cells. The activation of TRPA1 by luminal irritants is enhanced when the protective mucus layer is compromised. Villus EC cells also signal damage through a distinct mechanism, whereby oxidative stress activates TRPM2 channels, which leads to the release of both serotonin and ATP and consequent excitation of sensory nerve fibres. This topological segregation of EC cell functionality along the mucosal architecture constitutes a mechanism for the surveillance, maintenance and protection of gut integrity under diverse physiological conditions.

The microbiota-gut-brain axis has been proposed as a potential modulator of mood disorders such as major depression. Complex bidirectional biochemical activities in this axis have been posited to participate in adverse mood disorders. Environmental and genetic factors have dominated recent discussions on depression. The prescription of antibiotics, antidepressants, adverse negative DNA methylation reactions and a dysbiotic gut microbiome have been cited as causal for the development and progression of depression. While research continues to investigate the microbiome-gut-brain axis, this review will explore the state of persistence of gut bacteria that underpins bacterial dormancy, possibly due to adverse environmental conditions and/or pharmaceutical prescriptions. Bacterial dormancy persistence in the intestinal microbial cohort could affect the role of bacterial epigenomes and DNA methylations. DNA methylations are highly motif driven exerting significant control on bacterial phenotypes that can disrupt bacterial metabolism and neurotransmitter formation in the gut, outcomes that can support adverse mood dispositions.

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood-brain barrier dysfunction, and disruptions in neurotransmitter systems. The article highlights how inflammatory mediators influence brain regions implicated in mood regulation, such as the hippocampus, amygdala, and prefrontal cortex. The review further discusses the involvement of the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the kynurenine pathway, providing mechanistic insights into how chronic inflammation may underlie emotional and cognitive symptoms of depression. The bidirectional relationship between inflammation and depressive symptoms is emphasized, along with the role of peripheral immune responses and systemic stress. By integrating molecular, cellular, and neuroendocrine perspectives, this review supports the growing field of immunopsychiatry and lays the foundation for novel diagnostic biomarkers and anti-inflammatory treatment approaches in depression. Further research in this field holds promise for developing more effective and personalized interventions for individuals suffering from depression.

The microbiota-gut-brain-axis (MGBA) plays a role in the aetiology of mental disorders. Depression, a leading cause of disability worldwide, may be improved by probiotics. The aim of this narrative review is to investigate and synthesize the current evidence linking probiotic food supplementation with depressive symptomology.

The gut and the brain communicate and interact via the MGBA through inflammation and the immune system, short chain fatty acid production, neuronal innervation and activation as well as endocrine and neurotransmitter modulation. Dysregulation of gut-brain pathways are caused by gut dysbiosis and implicated in the onset, persistence and exacerbation of depression related symptoms. Modulation of the gut microbiota via administration of probiotics has shown to reduce depressive symptom severity with Bifidobacterium and Lactobacillus strains being the most reported. Probiotics may produce greater benefits in mild depression rather than in chronic, treatment resistant depression. Probiotic supplementation is a promising and safe approach for the prevention of severe depressive disorders in high-risk individuals such as people with subthreshold depression. However, the mechanistic pathways of the MGBA require further investigation and additional human clinical trials are necessary to evaluate the role of probiotics on depression.

Vinegar intake reportedly has an antihypertensive effect and reduces visceral fat. Nonetheless, studies on the form of vinegar intake and its effect on defecation are scarce. This cross-sectional study aimed to investigate the association between the frequency of vinegar-based dish intake and defecation status using data from the Tarumizu cohort study. The participants (n = 1024, 634 women) responded to a health check survey in 2019 using a brief-type self-administered diet history questionnaire. The association between the frequency of vinegar-based dish intake and defecation status was examined using a multivariate logistic regression analysis. Considering confounding factors influencing the defecation status such as sex, age, dietary fiber intake, and medication history, individuals with a habit of eating vinegar-based dishes, such as "sour main dishes" (odds ratio [OR]: 1.38; p = 0.039), "sunomono" (OR: 1.49; p = 0.035), and "salad with sour dressing" (OR: 1.41; p = 0.049), had a significantly higher defecation frequency. No significant association was observed between the habit of eating vinegar-based dishes and the time required for defecation or straining during defecation. Our study showed that the habit of eating vinegar-based dishes was positively associated with defecation status. Our findings may suggest a novel approach for defecation improvement in people with defecation problems.

Gallic acid (GA) is recognized for its purported antiinflammatory properties. GA has been demonstrated to prevent and alleviate the symptoms of chronic colitis through the modulation of the gut microbiota, improvement of the intestinal barrier, and reduction of inflammation.

In order to determine the mechanism by which GA exerts its protective effect against chronic colitis, mice were induced by dextran sulfate sodium (DSS). The reduction in the disease activity index by 25% and the decrease in colon tissue damage indicated that 36 days of GA intervention alleviated chronic DSS-induced colitis symptoms. GA was observed to mitigate weight loss by 2.5% and the shortening of colon by 17.3%, and to diminish the expression of pivotal proteins within the TLR4/nuclear factor κB (NF-κB) signaling cascades, consequently lowering the generation of inflammatory cytokines. Furthermore, GA effectively corrected the gut microbiota imbalance, increased the content of short-chain fatty acids (SCFAs), which in turn suppressed inflammation, and enhanced tight junction protein expression, thereby strengthening the intestinal barrier.

GA has the capacity to enhance the efficacy of chronic colitis through a multifaceted mechanism, influencing the gut microbiota, intestinal barrier function, and inflammatory processes. The findings highlight the potential of GA as a preventative strategy for chronic colitis.

Background/Objectives: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction, communication, and repetitive behaviors. Recent evidence indicates a significant relationship between ASD and imbalances in microbiota, particularly in the oral and gastrointestinal areas. This review examines the impact of oral microbiota, self-injurious behaviors (SIB), sensory sensitivity, and dietary choices on the comorbidities associated with ASD. Methods: An extensive literature review was conducted using PubMed and Scopus. The focus was on human studies with full-text availability, utilizing search terms related to ASD, oral health, oral microbiota, and neurodevelopmental disorders. The research was evaluated for methodological quality and its relevance to the connections between microbiota, oral health, and ASD. Results: Individuals with ASD face unique oral health challenges, including injuries from self-injurious behaviors and increased sensory sensitivity, which complicate oral hygiene and care. Selective eating can lead to nutritional deficiencies and worsen oral health issues. Dysbiosis in oral and gut microbiota, marked by altered levels of acetate, propionate, and butyrate, interferes with gut-brain and oral-brain connections, contributing to behavioral and neurological symptoms. Treatment options such as probiotics, fecal microbiota transfer, and sensory integration therapies can potentially alleviate symptoms and improve quality of life. Conclusions: The relationship between ASD, oral health, and microbiota suggests a bidirectional influence through neuroinflammatory mechanisms and metabolic disturbances. Proactive strategies focusing on microbiota and dental health may help reduce comorbidities and enhance the overall management of ASD, underscoring the need for further research into microbiota-host interactions and their therapeutic potential.

The gut microbiota-brain axis is a complex system that links the bacteria in our gut with our brain, it plays a part in what way we respond to stress. This chapter explores how stress affects the types of bacteria in the gut and shows the two-way connection between them. Stress can change the bacteria in our gut, which can cause various problems related to stress, like depression, anxiety, and irritable bowel syndrome (IBS). Figuring out how these interactions may help us develop new treatments that focus on the connection between gut bacteria and the brain. This chapter looks at how gut bacteria could help identify stress-related problems. It also discusses the difficulties and possibilities of using this research in medical practice. In the end, the chapter talks about what comes next in this quickly changing area. It highlights how important it is to include research about the gut-brain connection in overall public health plans.

Globally, master's and doctoral students, especially pregraduate students, are under great pressure. Probiotics are emerging as a promising intervention to improve mental health via gut-brain axis.

The aim of this study was to explore the impact of Lacticaseibacillus paracasei K56 supplementation on perceived stress among pregraduate students.

We conducted a double-blind, randomized, placebo-controlled trial in 120 healthy master's and doctoral students who faced graduation. Participants were randomly assigned to either probiotics (containing Lacticaseibacillus paracasei K56 6 × 1010 CFU / d) or placebo group for 2 weeks intervention. The main outcome was perceived stress assessed using Cohen's Perceived Stress Scale-10 (PSS-10). The secondary outcomes were stress, depression, and anxiety assessed by Depression, Anxiety and Stress Scales (DASS), gastrointestinal symptoms, and sleep evaluated by corresponding scales. These outcomes were assessed at baseline, 1, and 2 weeks. Pre- and post-treatment serum biomarkers, gut microbiota composition and metabolites were also detected.

There was no difference in changes of PSS-10 scores from baseline to 2 weeks between the K56 groups and the placebo [mean (standard error): -1.68 (0.48) vs. -0.39 (0.46), p = 0.055]. Furthermore, the K56 group exhibited superior reductions in both stress [-2.15 (0.38) vs. -0.96 (0.49), p = 0.035] and anxiety symptoms [-1.54 (0.32) vs. 0.53 (0.43), p = 0.003] via DASS compared with the placebo group. Additionally, those receiving K56 also experienced improved sleep quality (p = 0.010) and elevated levels of serotonin (5-HT) (p = 0.038) compare to placebo group. Moreover, taking probiotics K56 could modulate the pressure-induced changes in gut microbiota composition, particularly by increasing the beneficial bacteria (Lacticaseibacillus and Lacticaseibacillus paracasei), while suppressing suspected pathogenic bacteria (Shieglla and Escherichia_coli). Metabolomic analysis revealed an increased in metabolites, especially butyric acid in the K56 group (p = 0.035). Notably, there was a significant negative correlation between relative abundance of lactobacillus and stress-related symptoms, whereas butyric acid showed a significant positive correlation with lactobacillus abundance level.

This study suggested the potential benefits of K56 supplementation in alleviating stress and significant effect in reducing anxiety and insomnia among master's and doctoral students, which may be attributed to K56-induced changes in microbial composition and butanoate metabolism.

Chictr.org.cn, identifier ChiCTR2300078447.

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain-gut-microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain-gut-microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain-gut-microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain-gut-microbiome axis.

Exercise is a widely recognized non-pharmacological treatment for Parkinson's Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system.

This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research.

This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk-such as the brain-gut-muscle and brain-gut-bone axes-are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.

Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.