Therapeutic approaches targeting the gut microbiota in ischemic stroke: current advances and future directions.

Ischemic stroke (IS) is the predominant form of stroke pathology, and its clinical management remains constrained by therapeutic time frame. The gut microbiota (GM), comprising a multitude of bacterial and archaeal cells, surpasses the human cell count by approximately tenfold and significantly contributes to the human organism's growth, development, and overall well-being. The microbiota-gut-brain axis (MGBA) in recent years has established a strong association between gut microbes and the brain, demonstrating their intricate involvement in the progression of IS. The regulation of IS by the GM, encompassing changes in composition, abundance, and distribution, is multifaceted, involving neurological, endocrine, immunological, and metabolic mechanisms. This comprehensive understanding offers novel insights into the therapeutic approaches for IS. The objective of this paper is to examine the mechanisms of interaction between the GM and IS in recent years, assess the therapeutic effects of the GM on IS through various interventions, such as dietary modifications, probiotics, fecal microbiota transplantation, and antibiotics, and offer insights into the potential clinical application of the GM in stroke treatment.

Exploring the pathogenesis of insomnia and acupuncture intervention strategies based on the microbiota-gut-brain axis.

Insomnia is a common sleep disorder observed in clinical settings, with a globally rising prevalence rate. It not only impairs sleep quality and daytime functioning but also contributes to a range of physiological and psychological conditions, often co-occurring with somatic and mental disorders. Currently, the pathophysiology of this condition is not fully understood. Treatment primarily involves symptomatic management with benzodiazepine receptor agonists, melatonin and its receptor agonists, sedative antidepressants, atypical antipsychotics, and orexin receptor antagonists. However, due to the adverse side effects of these drugs, including dependency, addiction, and tolerance, there is an urgent need for safer, more effective, and environmentally friendly treatment methods. In recent years, research on the microbiota-gut-brain axis has received significant attention and is expected to be key in uncovering the pathogenesis of insomnia. Acupuncture stimulates acupoints, activating the body's intrinsic regulatory abilities and exerting multi-pathway, multi-target regulatory effects. A substantial body of evidence-based research indicates that acupuncture is effective in treating insomnia. However, the unclear mechanisms of its action have limited its further clinical application in insomnia treatment. Therefore, this study aims to elucidate the pathogenesis of insomnia from the perspective of the microbiota-gut-brain axis by examining metabolic, neuro-endocrine, autonomic nervous, and immune pathways. Additionally, this study discusses the comprehensive application of acupuncture in treating insomnia, aiming to provide new strategies for its treatment.

Microbiota-gut-brain axis in health and neurological disease: Interactions between gut microbiota and the nervous system.

Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.

Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights.

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-ß plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

The Effect of Probiotics and Microbiota on Nervous System and Mental Illnesses.

The microbiota that inhabits the gastrointestinal tract has been linked to various gastrointestinal and non-gastrointestinal disorders. Scientists have been studying how the bacteria in our intestines have an effect on our brain and nervous system. This connection is called the "microbiota- gut-brain axis". Given the capacity of probiotics, which are live non-pathogenic microorganisms, to reinstate the normal microbial population within the host and confer advantages, their potential impact has been subjected to scrutiny with regard to neurological and mental conditions. Material sourced for this review included peer-reviewed literature annotated in the PubMed, Web of Science, Scopus, and Google Scholar databases. The result has indicated the integration of probiotics into a child's diet to enhance the neuro-behavioral symptoms. Notwithstanding this, the current data set has been found to be insufficient and inconclusive. The potential utility of probiotics for the prevention or treatment of neurologic and mental disorders has become a subject of substantial interest.

Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC-MS metabolomics analysis.

Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC-MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague-Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

The Potential Role of Mitochondria in the Microbiota-Gut-Brain Axis: Implications for Brain Health.

Mitochondria are crucial organelles that regulate cellular energy metabolism, calcium homeostasis, and oxidative stress responses, playing pivotal roles in brain development and neurodegeneration. Concurrently, the gut microbiota has emerged as a key modulator of brain physiology and pathology through the microbiota-gut-brain axis. Recent evidence suggests an intricate crosstalk between the gut microbiota and mitochondrial function, mediated by microbial metabolites that can influence mitochondrial activities in the brain. This review aims to provide a comprehensive overview of the emerging role of mitochondria as critical mediators in the microbiota-gut-brain axis, shaping brain health and neurological disease pathogenesis. We discuss how gut microbial metabolites such as short-chain fatty acids, secondary bile acids, tryptophan metabolites, and trimethylamine N-oxide can traverse the blood-brain barrier and modulate mitochondrial processes including energy production, calcium regulation, mitophagy, and oxidative stress in neurons and glial cells. Additionally, we proposed targeting the mitochondria through diet, prebiotics, probiotics, or microbial metabolites as a promising potential therapeutic approach to maintain brain health by optimizing mitochondrial fitness. Overall, further investigations into how the gut microbiota and its metabolites regulate mitochondrial bioenergetics, dynamics, and stress responses will provide valuable insights into the microbiota-gut-brain axis in both health and disease states.

Phlorizin ameliorates cognitive and behavioral impairments via the microbiota-gut-brain axis in high-fat and high-fructose diet-induced obese male mice.

The long-term high-fat, high-sugar diet exacerbates type 2 diabetes mellitus (T2DM)-related cognitive impairments. Phlorizin, a well-studied natural compound found in apples and other plants, is recognized for its bioactive properties, including modulation of glucose and lipid metabolism. Despite its established role in mitigating metabolic disorders, the neuroprotective effects of phlorizin, particularly against diabetes-related cognitive dysfunction, have not been fully elucidated. Therefore, the present study aimed to investigate the effect of dietary supplementation of phlorizin on high-fat and high-fructose diet (HFFD)-induced cognitive dysfunction and evaluate the crucial role of the microbiota-gut-brain axis. We found that dietary supplementation of phlorizin for 14 weeks effectively prevented glucolipid metabolism disorder, spatial learning impairment, and memory impairment in HFFD mice. In addition, phlorizin improved the HFFD-induced decrease in synaptic plasticity, neuroinflammation, and excessive activation of microglia in the hippocampus. Transcriptomics analysis shows that the protective effect of phlorizin on cognitive impairment was associated with increased expression of neurotransmitters and synapse-related genes in the hippocampus. Phlorizin treatment alleviated colon microbiota disturbance, mainly manifested by an increase in gut microbiota diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria. The level of microbial metabolites, including SCFA, inosine 5'-monophosphate (IMP), and D (-)-beta-hydroxybutyric acid (BHB) were also significantly increased after phlorizin treatment. Integrating multiomics analysis observed tight connections between phlorizin-regulated genes, microbiota, and metabolites. Furthermore, removal of the gut microbiota via antibiotics treatment diminished the protective effect of phlorizin against HFFD-induced cognitive impairment, underscoring the critical role of the gut microbiota in mediating cognitive behavior. Importantly, supplementation with SCFA and BHB alone mimicked the regulatory effects of phlorizin on cognitive function. Therefore, phlorizin shows promise as a potential nutritional therapy for addressing cognitive impairment associated with metabolic disorders. Further research is needed to explore its effectiveness in preventing and alleviating neurodegenerative diseases.

Microbiota-gut-brain axis: Natural antidepressants molecular mechanism.

BACKGROUND: Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis. PURPOSE: This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain. METHODS: To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis. CONCLUSIONS: NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.

Causal associations between gut microbiota, circulating inflammatory proteins, and epilepsy: a multivariable Mendelian randomization study.

Background: Previous studies have suggested that gut microbiota (GM) may be involved in the pathogenesis of epilepsy through the microbiota-gut-brain axis (MGBA). However, the causal relationship between GM and different epilepsy subtypes and whether circulating inflammatory proteins act as mediators to participate in epileptogenesis through the MGBA remain unclear. Therefore, it is necessary to identify specific GM associated with epilepsy and its subtypes and explore their underlying inflammatory mechanisms for risk prediction, personalized treatment, and prognostic monitoring of epilepsy. Methods: We hypothesized the existence of a pathway GM-inflammatory proteins-epilepsy. We found genetic variants strongly associated with GM, circulating inflammatory proteins, epilepsy and its subtypes, including generalized and partial seizures, from large-scale genome-wide association studies (GWAS) summary data and used Multivariate Mendelian Randomization to explore the causal relationship between the three and whether circulating inflammatory proteins play a mediating role in the pathway from GM to epilepsy, with inverse variance weighted (IVW) method as the primary statistical method, supplemented by four methods: MR-Egger, weighted median estimator (WME), Weighted mode and Simple mode. Results: 16 positive and three negative causal associations were found between the genetic liability of GM and epilepsy and its subtypes. There were nine positive and nine negative causal associations between inflammatory proteins and epilepsy and its subtypes. Furthermore, we found that C-X-C motif chemokine 11 (CXCL11) levels mediated the causal association between Genus Family XIII AD3011 group and epilepsy. Conclusion: Our study highlights the possible causal role of specific GM and specific inflammatory proteins in the development of epilepsy and suggests that circulating inflammatory proteins may mediate epileptogenesis through the MGBA.

Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion.

Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the "microbiota-gut-brain" axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the g__Bacteroides and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host's feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host's feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host's feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.

Gut microbiota and eating behaviour in circadian syndrome.

Eating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut-brain axis signalling. We also explore potential mechanisms underlying the effects of altered gut microbiota on food intake behaviour and circadian rhythmicity. Understanding the crosstalk between gut microbiota, circadian rhythms, and unhealthy eating behaviour is crucial to addressing the obesity epidemic, which remains one of the biggest societal challenges of our time.

Deciphering the microbial map and its implications in the therapeutics of neurodegenerative disorder.

Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota's significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health-different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.

Bulimia Nervosa and Depression, from the Brain to the Gut Microbiota and Back.

Bulimia nervosa (BN) is a condition marked by a typical cyclical behavioural activity, characterized by restrictions, binges and vomiting, as well as a disturbance of the emotional value of food. Food stimuli acquire excessive relevance, giving rise to a succession of states of excitement and anxiety. The depressive condition accompanies very often BN. Most people with BN also experience one or more anxiety disorders. The aim of the review is to identify a link at a central and peripheral level that connects an eating disorder with a mood state. Altered nervous mechanisms are involved in BN. Among the cerebral areas, the insula is functionally compromised in BN. The insula is also implicated in depressive states. The insula is the primary gustatory cortex, where gustatory sensory information such as taste discrimination and higher cognitive functions such as food anticipation and reward are processed. The insula is anatomically connected to a wide range of cortical, limbic and paralimbic structures, and functionally implicated in high-order cognition, emotional responses, and empathic processes. The insula plays a crucial role in empathy, or in the ability to share the emotional states of others, and in particular negative emotions. In fact, the insular cortex is also activated in conditions of anxiety and depression. One of the pathophysiological factors that influences bulimia and depression is the composition of gut microbiota, as there is a strong association between the microbial signature and the brain function. Gut dysbiosis condition may contribute to the development of eating disorders, including BN. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of eating disorders. From this emerges the importance of adequate probiotic integration as a preventive and/or therapeutic tool in these pathologies.

Disrupted gut harmony in attention-deficit/hyperactivity disorder: Dysbiosis and decreased short-chain fatty acids.

Background: Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder with complex genetic and environmental underpinnings. Emerging evidence suggests a significant role of gut microbiota in ADHD pathophysiology. This study investigates variations in gut microbiota composition and Short-Chain Fatty Acid (SCFA) profiles between children and adolescents with ADHD and healthy controls. Methods: The study included 42 ADHD patients and 31 healthy controls, aged 6-18 years. Fecal samples were analyzed for microbial composition using 16S rRNA gene sequencing and for SCFA profiles through gas chromatography-mass spectrometry (GC-MS). The study assessed both α and ß diversity of gut microbiota and quantified various SCFAs to compare between the groups. Results: ADHD subjects demonstrated significantly reduced gut microbiota diversity, as indicated by lower α-diversity indices (Shannon index, Observed species, Faith PD index) and a trend towards significance in ß-diversity (Weighted UniFrac). Notably, the ADHD group exhibited significantly lower levels of key SCFAs, including acetic, propionic, isobutyric, isovaleric, and valeric acids, highlighting a distinct microbial and metabolic profile in these individuals. Conclusion: This study uncovers significant alterations in gut microbiota and SCFA profiles in children with ADHD, compared to healthy controls. The observed changes in SCFAs, known for their associations with other behavioral and neurologic pathologies, and for their role in neural signaling. These findings offer a metabolite fingerprint that could potentially lead to novel diagnostic and treatment approaches for ADHD, emphasizing the importance of gut microbiota in the disorder's pathogenesis and management.

The Antidepressant- and Anxiolytic-Like Effects of the Phosphodiesterase Type-5 Inhibitor Tadalafil are Associated with the Modulation of the Gut-Brain Axis During CNS Autoimmunity.

Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients.

Microbiota-gut-brain axis: interplay between microbiota, barrier function and lymphatic system.

The human gastrointestinal tract, boasting the most diverse microbial community, harbors approximately 100 trillion microorganisms comprising viruses, bacteria, fungi, and archaea. The profound genetic and metabolic capabilities of the gut microbiome underlie its involvement in nearly every facet of human biology, from health maintenance and development to aging and disease. Recent recognition of microbiota - gut - brain axis, referring to the bidirectional communication network between gut microbes and their host, has led to a surge in interdisciplinary research. This review begins with an overview of the current understandings regarding the influence of gut microbes on intestinal and blood-brain barrier integrity. Subsequently, we discuss the mechanisms of the microbiota - gut - brain axis, examining the role of gut microbiota-related neural transmission, metabolites, gut hormones and immunity. We propose the concept of microbiota-mediated multi-barrier modulation in the potential treatment in gastrointestinal and neurological disorders. Furthermore, the role of lymphatic network in the development and maintenance of barrier function is discussed, providing insights into lesser-known conduits of communication between the microbial ecosystem within the gut and the brain. In the final section, we conclude by describing the ongoing frontiers in understanding of the microbiota - gut - brain axis's impact on human health and disease.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 µmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1ß and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Behavioral dysregulation in Nile tilapia (Oreochromis niloticus, GIFT) post-Streptococcus agalactia infection: Role of the microbiota-gut-brain axis.

In the aquatic farming industry, understanding the factors affecting fish behavior is crucial, particularly in response to infections that compromise welfare and productivity. Swimming performance is a key life history trait critical to their ecology. This study explores the swimming behavior imbalance in Nile tilapia (Oreochromis niloticus, GIFT) post-infection with Streptococcus agalactiae (GBS), a common pathogen responsible for significant losses in aquaculture. We focused on how the microbiota-gut-brain axis influences the behavioral response of tilapia to GBS infection. Behavioral changes were quantified by measuring collision times and swimming speeds, which decreased significantly following infection. This behavioral downturn is mediated by alterations in the microbiota-gut-brain axis, evidenced by increased levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain and intestinal tissues. The study utilized pharmacological agents, the 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635), to investigate their efficacy in mitigating these behavioral and biochemical changes. Both agents partially restored normal behavior by adjusting neurotransmitter concentrations disrupted by GBS infection. Additionally, a notable increase in the relative abundance of Streptococcus within the gut microbiota of infected fish highlights the potential role of specific bacterial populations in influencing host behavior. This research provides novel insights into the complex interactions between pathogen-induced gut microbiota changes and Nile tilapia's behavioral outcomes, highlighting potential avenues for improving fish health management through microbiota-targeted interventions.

The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases.

The Aryl hydrocarbon receptor (AHR) is a cytosolic receptor and ligand-activated transcription factor widely expressed across various cell types in the body. Its signaling is vital for host responses at barrier sites, regulating epithelial renewal, barrier integrity, and the activities of several types of immune cells. This makes AHR essential for various cellular responses during aging, especially those governing inflammation and immunity. In this review, we provided an overview of the mechanisms by which the AHR mediates inflammatory response at gut and brain level through signals from intestinal microbes. The age-related reduction of gut microbiota functions is perceived as a trigger of aberrant immune responses linking gut and brain inflammation to neurodegeneration. Thus, we explored gut microbiome impact on the nature and availability of AHR ligands and outcomes for several signaling pathways involved in neurodegenerative diseases and age-associated decline of brain functions, with an insight on Parkinson's and Alzheimer's diseases, the most common neurodegenerative diseases in the elderly. Specifically, we focused on microbial tryptophan catabolism responsible for the production of several AHR ligands. Perspectives for the development of microbiota-based interventions targeting AHR activity are presented for a healthy aging.