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Alzheimer's Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic-pituitary-adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila's impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 10 9 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and synaptic dysfunction. Emerging evidence suggests a significant relationship between gut microbiota and brain health, mediated through the gut-brain axis. Alterations in gut microbiota composition may influence AD progression by affecting molecular pathways and miRNA interactions., Methods: We retrieved and analyzed microarray data from 34 tissue samples of AD patients and controls (GEO accession number GSE110298). Differentially expressed genes (DEGs) with the GCS score package in R, considering a p-value < 0.05 and logFC<-1 and logFC>1 to isolate significant gene clusters. Enrichment analysis of signaling pathways and gene ontology was conducted using Enrichr, KEGG, Panther, DAVID, and shiny GO databases. Protein-protein interactions were visualized with Networkanalyst and CytoScape. Gut microbiota in 200 CE patients was analyzed using next-generation sequencing (NGS) data from gutMDisorder and GMrepo databases. miRNA interactions were evaluated using miEAA, Targetscan, MienTurnet, and miRnet databases., Results: Significant reductions in microbial taxa, including Clostridia (LDA score -4.878208), Firmicutes (LDA score -4.817032), and Faecalibacterium (LDA score -4.40714), were observed in AD patients. Pathway analysis highlighted the involvement of Axon guidance, ErbB, and MAPK signaling pathways in AD. Venn diagram analysis identified 619 intersecting genes in brain and gut tissues, emphasizing pathways such as Axon Guidance and Cell Cycle. miRNA analysis revealed important regulatory miRNAs, including hsa-let-7c, hsa-mir-125b-2, and hsa-mir-145, which target key transcription factors involved in AD pathology., Conclusion: The study demonstrates significant dysbiosis in the gut microbiota of AD patients and underscores the potential role of gut microbiota in AD progression through altered signaling pathways and miRNA interactions. These findings highlight the need for further research into microbiota-based interventions as potential therapeutic strategies for AD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Numerous studies conducted over the last ten years have shown a strong correlation between the gut microbiota and the onset and progression of Alzheimer's disease (AD). However, the exact underlying mechanism is still unknown. An ongoing communication mechanism linking the gut and the brain is highlighted by the term "microbiota-gut-brain axis," which was originally coined the "gut-brain axis." Key metabolic, endocrine, neurological, and immunological mechanisms are involved in the microbiota‒gut‒brain axis and are essential for preserving brain homeostasis. Thus, the main emphasis of this review is how the gut microbiota contributes to the development of AD and how various natural products intervene in this disease. The first part of the review provides an outline of various pathways and relationships between the brain and gut microbiota, and the second part provides various mechanisms involved in the gut microbiota and AD. Finally, this review provides knowledge about natural products and their effectiveness in treating gut microbiota-induced AD. AD may be treated in the future by altering the gut microbiota with a customized diet, probiotics/prebiotics, plant products, and natural products. This entails altering the microbiological partners and products (such as amyloid protein) that these partners generate., Competing Interests: Declaration of competing interest The authors declare no competing interests.Looking forward for a positive and rapid processing of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Prior efforts have revealed changes in gut microbiome, circulating metabolome, and multimodal neuroimaging features in cerebral small vessel disease (CSVD). However, there is a paucity of research integrating the multi-omic information to characterize the role of the microbiota-gut-brain axis in CSVD., Methods: We collected gut microbiome, fecal and blood metabolome, multimodal magnetic resonance imaging data from 37 CSVD patients with white matter hyperintensities and 46 healthy controls. Between-group comparison was performed to identify the differential gut microbial taxa, followed by performance of multi-stage microbiome-metabolome-neuroimaging-neuropsychology correlation analyses in CSVD patients., Results: Our data showed both depleted and enriched gut microbes in CSVD patients. Among the differential microbes, Haemophilus and Akkermansia were associated with a range of metabolites enriched for Aminoacyl-tRNA biosynthesis pathway. Furthermore, the affected metabolites were associated with neuroimaging measures involving gray matter morphology, spontaneous intrinsic brain activity, white matter integrity, and global structural network topology, which were in turn related to cognition and emotion in CSVD patients., Conclusion: Our findings provide an integrative framework to understand the pathophysiological mechanisms underlying the interplay between gut microbiota dysbiosis and CSVD, highlighting the potential of targeting the microbiota-gut-brain axis as a therapeutic strategy in CSVD patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

Background & Aim: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women throughout their reproductive age and characterised via polycystic ovaries, hyperandrogenism, and irregular menstruation. There is rising evidence that the pathophysiology of PCOS is significantly affected via the gut microbiota and its metabolic products., Methods: This narrative review synthesizes current literature exploring the relationship between gut microbiota and PCOS. A comprehensive search of electronic databases was conducted to identify relevant studies. Further this review also analysed therapeutic options of probiotics, prebiotics, Fecal Microbiota Transplant (FMT), high fiber and poly phenol rich diet and novel therapeutic agents in treatment of PCOS., Results: Emerging evidence suggests alterations in the composition and diversity of gut microbiota in women with PCOS. The current literature showed a complex relationship of gut microbiota, short chain fatty acids (SCFAs) metabolism, intestinal permeability and LPS (Lipid Polysaccharide) metabolism, gut-brain axis and bile acid (BA) pathway within etiology and pathophysiology of PCOS. Additionally, the factors such as diet, lifestyle, genetics, and environmental influences may all contribute to alterations in gut microbiota that could potentially exacerbate or mitigate PCOS symptoms., Conclusion: The review provides valuable insights into the intricate interplay between the gut and female reproductive health. The present evidence suggested that alterations in diversity and function of the gut microbiota may lead to specific pathogenic changes that lead to development of PCOS. A comprehensive understanding of these microbial dynamics may lead to new therapeutic approaches that target the gut micro biome., Competing Interests: Conflict of interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Rationale: Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation., Objective: The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities., Results: Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions., Conclusion: In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes., Competing Interests: Declarations Ethical approval This work is a review paper, and thus, no ethical approval is required. Competing interests The authors assert that they do not have any known financial interests or personal relationships that could be perceived as influencing the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: The incidence of obesity increases annually. It is closely related to the occurrence of cardiovascular diseases, malignant tumors, etc., and has become a major global health problem. 5-hydroxytryptamine (5-HT), a multifunctional monoamine neurotransmitter, is dispersed throughout the central nervous system and digestive tract. It is intimately related to the mechanism of obesity., Materials and Methods: PubMed, Web of Science and Embase were carefully searched. We collected articles that are closely related to 5-HT, the gut-brain axis, and obesity., Key Fingdings: The gut microbiota not only influences nutrient metabolism but also centrally meditates appetite and mood regulation. The gut-brain axis, a system connecting the gut and the brain, is known to participate in two-way communication between the gut flora and the central nervous system., Significance: There have been few reports on whether peripheral and central 5-HT interact bidirectionally via the gut-brain axis and jointly play a role in the pathogenesis of obesity. In this review, we summarize the rationale for the contribution of the 5-HT-related gut-brain axis to the development of obesity and explore feasible signaling pathways, which elucidates new targets for preventing and treating obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms., Methods: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych)., Key Results: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2-class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty-two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%-97% for 2 clusters and 71-79% for 6 classes and 51%-63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non-DGBI (range 97% with 2 clusters to 65% with 22 classes) groups., Conclusions & Inferences: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits., (© 2024 John Wiley & Sons Ltd.)

Objective: Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice., Materials and Methods: A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours., Results: Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed., Conclusions: These results indicated that gut microbiota might affect host's inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. 'Limosilactobacillus-3-OMDP-IL-1β/IL-6' might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

Alzheimer's disease (AD) is a degenerative disease that causes a progressive decline in memory and thinking skills. Over the past few years, diverse studies have shown that there is no single cause of AD; instead, it has been reported that factors such as genetics, lifestyle, and environment contribute to the pathogenesis of the disease. In this sense, it has been shown that obesity during middle age is one of the most prominent modifiable risk factors for AD. Of the multiple potential mechanisms linking obesity and AD, the gut microbiota (GM) has gained increasing attention in recent years. However, the underlying mechanisms that connect the GM with the process of neurodegeneration remain unclear. Through this narrative review, we present a comprehensive understanding of how alterations in the GM of people with obesity may result in systemic inflammation and affect pathways related to the pathogenesis of AD. We conclude with an analysis of the relationship between GM and insulin resistance, a risk factor for AD that is highly prevalent in people with obesity. Understanding the crosstalk between obesity, GM, and the pathogenesis of AD will help to design new strategies aimed at preventing neurodegeneration.

Purpose of Review: The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions., Recent Findings: The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function., Summary: Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Depression is a multifaceted mental health disorder with complex etiology and significant global burden. Recent research indicates that the gut microbiota plays a role in the pathophysiology of depression, highlighting the potential role of specific bacterial species in influencing mood and cognitive function. In this study, we aimed to investigate the presence, copy numbers, and Ct values of selected bacterial species in stool samples from depressed patients (n=50) compared to control subjects (n=50). Our findings revealed significant differences in the abundance of Fusobacterium spp., Bifidobacterium spp., Lactobacillus spp., Bacteroidetes phylum, Firmicutes phylum, and Actinobacteria spp. between the two groups. Dysregulation of the gut microbiota, characterized by decreased presence of beneficial bacteria (e.g., Bifidobacterium spp., Lactobacillus spp.) and altered abundance of potentially pathogenic bacteria (e.g., Fusobacterium spp.), may contribute to the development or exacerbation of depression. These findings support the emerging concept of the gut-brain axis and its role in mental health. However, further research is needed to better understand the underlying mechanisms and explore the therapeutic potential of microbiota-targeted interventions for depression. Understanding the intricate interplay between the gut microbiota and depression could pave the way for novel treatment strategies and personalized approaches in mental health care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2024. Published by Elsevier Ltd.)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. A bidirectional communication system known as the "microbiota-gut-brain" axis has a regulatory function in neurodegenerative disorders. The impact of probiotics on ALS through the "microbiota-gut-brain" axis remains uncertain. A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in mutant superoxide dismutase 1 (SOD1 G93A ) transgenic mice models of ALS by using immunofluorescence and Western blotting. Subsequently, the mice were administered a multistrain probiotic mixture (LBE) or vehicle orally, starting from 60 days of age until the terminal stage of the disease. The effects of these agents on the behavior, gut microbiota, microbial metabolites, and pathological processes of the spinal and intestine of SOD1 G93A mice were analyzed, with a focus on exploring potential protective mechanisms. SOD1 G93A mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant superoxide dismutase 1 (SOD1) aggregation, and protected neuronal cells in the intestine and spinal cord of SOD1 G93A mice. Furthermore, LBE treatment resulted in a change in intestinal microbiota, an increase in short-chain fatty acid levels, and an enhancement in autophagy flux. SOD1 G93A mice exhibited various structural abnormalities in the intestine. LBE can improve the proinflammatory response, reduce aberrant SOD1 aggregation, and protect neuronal cells in the spinal cord and intestine of SOD1 G93A mice. The positive effect of LBE can be attributed to increased short-chain fatty acids and enhanced autophagy flux., Competing Interests: Declarations. Ethics Approval: All animal procedures were performed in accordance with the Regulations for the Administration of Laboratory Animals set forth by the Ministry of Science and Technology of the People’s Republic of China. All experiments were approved by the Research Ethics Committee of the Second Hospital of Hebei Medical University (Shijiazhuang, Hebei, P.R. China, protocol code: 2022AE269, date of approval: 2022.3.14). Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions., Competing Interests: Declarations. Ethics Approval: The studies involving human participants were reviewed and approved by the Ethics Committee of the Shanghai Jing’an Centre Hospital. All of the actions described in this study were conducted in accordance with ethical guidelines. Consent to Participate: The patients/participants provided written informed consent to participate in this study. Consent to Publish: Informed consent was obtained from the patients/participants for the publication of their anonymous information in this manuscript. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively., Competing Interests: Declarations Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable. Competing Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Unsupervised machine learning describes a collection of powerful techniques that seek to identify hidden patterns in unlabeled data. These techniques can be broadly categorized into dimension reduction, which transforms and combines the original set of measurements to simplify data, and cluster analysis, which seeks to group subjects based on some measure of similarity. Unsupervised machine learning can be used to explore alternative subtyping of disorders of gut-brain interaction (DGBI) compared to the existing gastrointestinal symptom-based definitions of Rome IV., Purpose: This present review aims to familiarize the reader with fundamental concepts of unsupervised machine learning using accessible definitions and provide a critical summary of their application to the evaluation of DGBI subtyping. By considering the overlap between Rome IV clinical definitions and identified clusters, along with clinical and physiological insights, this paper speculates on the possible implications for DGBI. Also considered are algorithmic developments in the unsupervised machine learning community that may help leverage increasingly available omics data to explore biologically informed definitions. Unsupervised machine learning challenges the modern subtyping of DGBI and, with the necessary clinical validation, has the potential to enhance future iterations of the Rome criteria to identify more homogeneous, diagnosable, and treatable patient populations., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The gut microbiota is an important factor responsible for the physiological processes as well as pathogenesis of host. The communication between central nervous system (CNS) and microbiota occurs by different pathways i.e., chemical, neural, immune, and endocrine. Alteration in gut microbiota i.e., gut dysbiosis causes alteration in the bidirectional communication between CNS and gut microbiota and linked to the pathogenesis of neurological and neurodevelopmental disorder. Therefore, now-a-days microbiota-gut-brain-axis (MGBA) has emerged as therapeutic target for the treatment of metabolic disorder. But, experimental data available on MGBA from basic research has limited application in clinical study. In present study we first summarized molecular mechanism of microbiota interaction with brain physiology and pathogenesis via collecting data from different sources i.e., PubMed, Scopus, Web of Science. Furthermore, evidence shows that adipose tissue (AT) is active during metabolic activities and may also interact with MGBA. Hence, in present study we have focused on the relationship among MGBA, brown adipose tissue, and white adipose tissue. Along with this, we have also studied functional specificity of AT, and understanding heterogeneity among MGBA and different types of AT. Therefore, molecular interaction among them may provide therapeutic target for the treatment of neurological disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Disorders of gut-brain interaction (DGBI) are common chronic conditions characterized by persistent and recurring gastrointestinal symptoms triggered by several pathophysiological factors, including an altered gut microbiota. The most common DGBI are irritable bowel syndrome (IBS), functional constipation (FC) and functional dyspepsia (FD). Recently, a deep understanding of the role of the gut microbiota in these diseases was possible due to multi-omics methods capable to provide a comprehensive assessment. Most of the therapies recommended for these patients, can modulate the gut microbiota such as diet, prebiotics, probiotics and non-absorbable antibiotics, which were shown to be safe and effective. Since patients complain symptoms after food ingestion, diet represents the first line therapeutic approach. Avoiding dietary fat and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and increasing the number of soluble fibers represent the therapeutic choices for FD, IBS and FC respectively. Probiotics, as a category, have been employed with good results in all the abovementioned DGBI. Rifaximin has been shown to be useful in the context of bowel related disorders, although a recent trial showed positive results for FD. Fecal microbiota transplantation has been tested for IBS and FC with promising results. In this review, we will briefly summarize the current understanding on dysbiosis and discuss microbiota modulation strategies to treat patients with DGBI., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms., Competing Interests: Declarations Ethical Approval Not applicable. Consent for publication Not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Antidepressants remain the first-line treatment for depression. However, the factors influencing medication response are still unclear. Accumulating evidence implicates an association between alterations in gut microbiota and antidepressant response. Therefore, the aim of this study is to investigate the role of the gut microbiota-brain axis in the treatment response of venlafaxine. After chronic social defeat stress and venlafaxine treatment, mice were divided into responders and non-responders groups. We compared the composition of gut microbiota using 16 S ribosomal RNA sequencing. Meanwhile, we quantified metabolomic alterations in serum and hippocampus, as well as hippocampal neurotransmitter levels using liquid chromatography-mass spectrometry. We found that the abundances of 29 amplicon sequence variants (ASVs) were significantly altered between the responders and non-responders groups. These ASVs belonged to 8 different families, particularly Muribaculaceae. Additionally, we identified 38 and 39 differential metabolites in serum and hippocampus between the responders and non-responders groups, respectively. Lipid, amino acid, and purine metabolisms were enriched in both serum and hippocampus. In hippocampus, the concentrations of tryptophan, phenylalanine, gamma-aminobutyric acid, glutamic acid, and glutamine were increased, while the level of succinic acid was decreased in the responders group, compared with the non-responders group. Our findings suggest that the gut microbiota may play a role in the antidepressant effect of venlafaxine by modulating metabolic processes in the central and peripheral tissues. This provides a novel microbial and metabolic framework for understanding the impact of the gut microbiota-brain axis on antidepressant response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE., Competing Interests: Declarations. Ethics Approval: Not applicable. Informed Consent: Not applicable. Conflict of Interest: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: GI-specific psychological factors are important contributors to patients' symptom experience and quality of life across all disorders of gut-brain interaction (DGBI). Clinicians' ability to recognize the role of these psychological factors is essential for formulating a biopsychosocial case conceptualization and informing treatment decisions., Purpose: This article will familiarize gastroenterology providers with conceptualizing the role of GI-specific psychological factors in DGBI and provides stepwise, practical guidance for how to assess these during clinical encounters in a time-efficient manner., (© 2024 John Wiley & Sons Ltd.)

Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent to Publish: Not applicable. Competing Interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Brain diseases, mainly including acute brain injuries, neurodegenerative diseases, and mental disorders, have posed a significant threat to human health worldwide. Due to the limited regenerative capability and the existence of the blood-brain barrier, the brain was previously thought to be separated from the rest of the body. Currently, various cross-talks between the central nervous system and peripheral organs have been widely described, including the brain-gut axis, the brain-liver axis, the brain-skeletal muscle axis, and the brain-bone axis. Moreover, several lines of evidence indicate that leveraging systemic biology intervention approaches, including but not limited to lifestyle interventions, exercise, diet, blood administration, and peripheral immune responses, have demonstrated a significant influence on the progress and prognosis of brain diseases. The advancement of innovative proteomic and transcriptomic technologies has enriched our understanding of the nuanced interplay between peripheral organs and brain diseases. An array of novel or previously underappreciated blood-derived factors have been identified to play pivotal roles in mediating these communications. In this review, we provide a comprehensive summary of blood-to-brain communication following brain diseases. Special attention is given to the instrumental role of blood-derived signals, positing them as significant contributors to the complex process of brain diseases. The insights presented here aim to bridge the current knowledge gaps and inspire novel therapeutic strategies for brain diseases., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Irritable bowel syndrome (IBS) remains a challenging condition both for patients and clinicians, characterized by its chronic nature and the elusive complexity of its underlying mechanisms. The multifaceted relationship between the neuroendocrine axis, gut microbiota, and inflammatory response has emerged as a focal point in recent research, offering new insights into the pathophysiology of IBS. The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut, often referred to as the "gut-brain axis". This bidirectional communication is essential for regulating gastrointestinal function, stress responses, and overall homeostasis. Dysregulation of this axis, as highlighted by elevated cortisol and serotonin levels in IBS patients, suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms. These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS, potentially guiding more effective, personalized treatment approaches. Equally important is the role of the gut microbiota, a diverse and dynamic ecosystem that directly impacts gut health. This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses. These findings align with the growing recognition that gut microbiota is a critical player in IBS, influencing both the disease's onset and progression., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia., Methods: Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment., Results: Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites., Conclusion: There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy., Competing Interests: Declatations. Ethical approval: This article does not contain any studies with animals performed by any of the authors. Informed consent: Since this study did not involve the usage of humans, therefore, there was no need for informed consent. Conflict of interest: Authors declare no conflict of interest related to the current work., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chronic constipation is a prevalent clinical condition. Its etiology and pathogenesis have not yet been fully understood. In recent years, mounting evidence suggests a close association between chronic constipation and intestinal dysbiosis, including alterations in the colony structure and metabolites, as well as the modulation of bowel movements via the brain-gut-microbiota axis. With the deepening of related research, probiotic-related therapies are expected to become a potential first-line treatment for chronic constipation in the future. In this review, we summarize the current research insights into the intricate relationships between chronic constipation and the gut microbiota and briefly discuss several different approaches for treating chronic constipation. The findings from this review may advance our understanding of the pathological mechanisms underlying chronic constipation and, ultimately, translate them into improvements in patient care., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As a multifunctional ecosystem, the human digestive system contains a complex network of microorganisms, collectively known as gut microbiota. This consortium composed of more than 10 13 microorganisms and Firmicutes and Bacteroidetes are the dominant microbes. Gut microbiota is increasingly recognized for its critical role in physiological processes beyond digestion. Gut microbiota participates in a symbiotic relationship with the host and takes advantage of intestinal nutrients and mutually participates in the digestion of complex carbohydrates and maintaining intestinal functions., Method and Result: We reviewed the neuroactive components produced by gut microbiota. Interestingly, microbiota plays a crucial role in regulating the activity of the intestinal lymphatic system, regulation of the intestinal epithelial barrier, and maintaining the tolerance to food immunostimulating molecules. The gut-brain axis is a two-way communication pathway that links the gut microbiota to the central nervous system (CNS) and importantly is involved in neurodevelopment, cognition, emotion and synaptic transmissions. The connections between gut microbiota and CNS are via endocrine system, immune system and vagus nerve., Conclusion: The gut microbiota produces common neurotransmitters and neuromodulators of the nervous system. These compounds play a role in neuronal functions, immune system regulation, gastrointestinal homeostasis, permeability of the blood brain barrier and other physiological processes. This review investigates the essential aspects of the neurotransmitters and neuromodulators produced by gut microbiota and their implications in health and disease., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethical approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders characterized by recurrent abdominal pain and altered bowel habits. The exact pathophysiological mechanisms for IBS development are not completely understood. Several factors, including genetic predisposition, environmental and psychological influences, low-grade inflammation, alterations in gastrointestinal motility, and dietary habits, have been implicated in the pathophysiology of the disorder. Additionally, emerging evidence highlights the role of gut microbiota in the pathophysiology of IBS. This review aims to thoroughly investigate how alterations in the gut microbiota impact physiological functions such as the brain-gut axis, immune system activation, mucosal inflammation, gut permeability, and intestinal motility. Our research focuses on the dynamic "microbiome shifts", emphasizing the enrichment or depletion of specific bacterial taxa in IBS and their profound impact on disease progression and pathology. The data indicated that specific bacterial populations are implicated in IBS, including reductions in beneficial species such as Lactobacillus and Bifidobacterium , along with increases in potentially harmful bacteria like Firmicutes and Proteobacteria. Emphasis is placed on the imperative need for further research to delineate the role of specific microbiome alterations and their potential as therapeutic targets, providing new insights into personalized treatments for IBS.

Interoception - the internal sensing of bodily states and their communication to the brain - has recently become a 'buzzword'. However, the scientific study of how the brain and the body communicate has a much longer and well-established history. In the 16 th century, the French philosopher and scientist René Descartes (1596-1650) proposed that the mind and body are two fundamentally distinct entities, yet they interact with each other to regulate animal and human behaviors. Descartes argued that the body, which operates like a machine and follows the laws of physics, is controlled by the mind (or the brain), the source of our cognitive functions. Today, it is widely recognized that the interactions between the body and brain are critical for our survival and overall well-being (Figure 1). At the same time, we are just beginning to learn about the mechanistic bases of these interactions. In this primer, we will discuss the origins of interoception research and how body-brain interactions govern some of our most critical homeostatic functions, such as energy balance. Given their key roles in health and disease, we will focus on the neural and hormonal pathways involved in gut-brain communication and their impact on feeding behavior and metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is characterized by social interaction deficits and repetitive behaviors. Recent research has linked that gut dysbiosis may contribute to ASD-like behaviors. However, the exact developmental time point at which gut microbiota alterations affect brain function and behavior in patients with ASD remains unclear. We hypothesized that ASD-related brain microstructural changes and gut dysbiosis induce metabolic dysregulation and proinflammatory responses, which collectively contribute to the social behavioral deficits observed in early childhood. We used an autistic-like rat model that was generated via prenatal valproic acid exposure. We analyzed brain microstructural changes using diffusion tensor imaging (DTI) and examined microbiota, blood, and fecal samples for inflammation biomarkers. The ASD model rats exhibited significant brain microstructural changes in the anterior cingulate cortex, hippocampus, striatum, and thalamus; reduced microbiota diversity (Prevotellaceae and Peptostreptococcaceae); and altered metabolic signatures. The shift in microbiota diversity and density observed at postnatal day (PND) 35, which is a critical developmental period, underscored the importance of early ASD interventions. We identified a unique metabolic signature in the ASD model, with elevated formate and reduced acetate and butyrate levels, indicating a dysregulation in short-chain fatty acid (SCFA) metabolism. Furthermore, increased astrocytic and microglial activation and elevated proinflammatory cytokines-interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)-were observed, indicating immune dysregulation. This study provided insights into the complex interplay between the brain and the gut, and indicated DTI metrics as potential imaging-based biomarkers in ASD, thus emphasizing the need for early childhood interventions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Micro- and nanoplastics (MNPs), emerging environmental pollutants, infiltrate marine, terrestrial, and freshwater systems via diverse pathways, culminating in their accumulation in the human body through food chain transmission, posing potential health risks. Researches have demonstrated that MNPs disrupt gut microbiota equilibrium and compromise intestinal barrier integrity, as well as traverse the blood-brain barrier, leading to brain damage. Moreover, the complex interaction between the gut and the nervous system, facilitated by the "gut-brain axis," indicates an additional pathway for MNPs-induced brain damage. This has intensified scientific interest in the intercommunication between MNPs and the gut-brain axis. While existing studies have documented microbial imbalances and metabolic disruptions subsequent to MNPs exposure, the precise mechanisms by which the microbiota-gut-brain axis contributes to MNPs-induced central nervous system damage remain unclear. This review synthesizes current knowledge on the microbiota-gut-brain axis, elucidating the pathogenesis of MNPs-induced gut microbiota dysbiosis and its consequent brain injury. It emphasizes the complex interrelation between MNPs and the microbiota-gut-brain axis, advocating for the gut microbiota as a novel therapeutic target to alleviate MNP-induced brain harm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alterations in commensal gut microbiota, such as butyrate-producing bacteria and its metabolites, have been linked to stress-related brain disorders, including depression. Herein, we investigated the effect of Faecalibacterium prausnitzii (ATCC-27766) administered along with fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in a rat model of treatment-resistant depression (TRD). The behavioral changes related to anxiety-, anhedonia- and despair-like phenotypes were recorded employing elevated plus maze, sucrose-preference test, and forced-swim test, respectively. Rats exposed to unpredictable chronic mild-stress (UCMS) and adrenocorticotropic hormone (ACTH) injections exhibited a TRD-like phenotype. Six-week administration of F. prausnitzii and FOS + GOS ameliorated TRD-like conditions in rats. This synbiotic treatment also restored the decreased levels of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate in the fecal samples of TRD rats. Synbiotic-recipient TRD rats displayed an increased abundance of Lactobacillus helveticus, Lactobacillus hamsteri, and Ruminococcus flavefaciens. Moreover, more mucus-producing goblet cells were seen in the colon of synbiotic-treated rats, suggesting improved gut health. The synbiotic treatment effectively modulated neuroinflammation by reducing proinflammatory cytokines (IFN-γ, TNF-α, CRP, and IL-6). It normalized the altered levels of key neurotransmitters such as serotonin, gamma-aminobutyric acid, noradrenaline, and dopamine in the hippocampus and/or frontal cortex. The enhanced expression of brain-derived neurotrophic factor, tryptophan hydroxylase 1, and serotonin transporter-3 (SERT-3), and reduced levels of indoleamine 2,3-dioxygenase 1 (IDO-1) and kynurenine metabolite were observed in the synbiotic-treated group. We suggest that F. prausnitzii and FOS + GOS-loaded synbiotic may reverse the TRD-like symptoms in rats by positively impacting gut health, neuroinflammation, neurotransmitters, and gut microbial composition., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest.We confirmed that all authors have read and approved the manuscript. We further confirm that all authors have approved the order of authors listed in the manuscript.We understand that the Corresponding Author is the sole contact for the Editorial process. He is responsible for communicating with another author about progress, submission of revisions, and final approval of proofs., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Rare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood-brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd 2 O 3 ) during pregnancy, and its involved mechanism of BGA injury., Methods: We used rat model to investigated the mechanisms of the offspring's neural damage that Nd 2 O 3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators., Results: Maternal Nd 2 O 3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring's neural development and weakening their spatial learning ability. Nd 2 O 3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd 2 O 3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability., Conclusion: Maternal exposure to Nd 2 O 3 affects the offspring's BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children's gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd 2 O 3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd 2 O 3 , such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jia, Cao, Guo, Wu, Du, Tang, Xia and Deng.)

The gut microbiota has been posited as a target for the treatment of major depressive disorder. Herein, we investigated the effect of the hydroethanolic leaf extract of Mallotus oppositifolius (MOE) on the gut microbiota of mice and how this contributes to its known antidepressant-like effect. A 6-week chronic unpredictable mild stress (CUMS) procedure was employed in 7 groups of mice to induce depression. From the third week, oral MOE treatments (10, 30, 100 mg/kg) and two reference drugs, fluoxetine (12 mg/kg) and minocycline (40 mg/kg), known to affect the gut microbiota, were administered. The sixth and seventh groups were the vehicle stressed (VEH-S) and non-stressed groups (VEH-NS). Changes in depressive-like behaviors were assessed using sucrose preference test while the forced swimming test (FST) was used to assess sustained antidepressant-effect after treatment discontinuation. Moreover, changes in prefrontal cortex (PFC) and hippocampal serotonin (5-HT) levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The effect of treatment on the profile of the gut microbiota of the groups was elucidated using 16S rRNA Oxford Nanopore sequencing. MOE and reference drugs reversed the depression-associated reduction in sucrose preference when compared to VEH-S. MOE (with peak effect at 30 mg/kg) reduced immobility while increasing swimming and climbing behaviors. MOE reversed CUMS-induced reduction of 5-HT concentration in PFC and hippocampus. The behavioral effects of MOE were associated with shifts in the gut microbiota of CUMS-exposed mice. The study has provided seminal evidence that MOE ameliorates CUMS-induced depressive symptoms by modulating gut microbiota and increasing brain 5-HT levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is caused by a variety of factors, and one of the most important factors is gut microbiota dysbiosis. An imbalance in the gut mincrobiota have been shown to change the concentrations of lipopolysaccharide and short-chain fatty acids. These microorganisms synthesize substances that can influence the levels of a variety of metabolites and cause multiple diseases through the immune response, fatty acid metabolism, and amino acid metabolism pathways. Furthermore, these metabolic changes promote the formation of β-amyloid plaques and neurofibrillary tangles. Thus, the microbiota-gut-brain axis plays an important role in AD development. In addition to traditional therapeutic drugs such as donepezil and memantine, traditional Chinese medicines (TCMs) have also showed to significantly decrease the severity of AD symptoms and suppress the underlying related mechanisms. We searched for studies on the effects of different herbal monomers, single herbs, and polyherbal formulas on the gut microbiota of AD patients and identified the relevant pathways through which the gut microbiota affected AD. We conclude that improvements in the gut microbiota not only decrease the occurrence of inflammatory reactions but also reduce the deposition of central pathological products. Herbal monomers have a stronger effect on improving of central pathology. Polyherbal formulas have the most extensive effect on the gut microbiota in patients with AD. Among the effects of formulas, the anti-inflammatory effect is the most essential and is also the main concern regarding the use of TCMs in treating AD from the viewpoint of the gut microbiota. We hope that this review will be helpful for providing new ideas for the clinical application of TCMs in the treatment of AD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications., Methods: In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 10 9 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals., Results: Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3)., Conclusion: Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting., Methods: We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024., Results: The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients., Conclusions: Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future., (© 2024 John Wiley & Sons Ltd.)

Purpose of Review: Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut-brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia., Recent Findings: Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut-brain therapies have shown promising results, especially virtual reality., Summary: The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Perinatal stage represents a critical period for brain development. Docosahexaenoic acid (DHA) is a ω-3 polyunsaturated fatty acid preferentially accumulated in the brain that may benefit neurodevelopment. Microbial colonization and maturation parallel with the rapid development of infant metabolic and brain function that may influence the effects of DHA on neurological development. This review aims to summarize the current literature on the mediating effects of DHA on brain and gut microbiome development and attempts to reevaluate the efficacy of DHA from a gut microbiome-mediated perspective. Specifically, the regulatory roles of DHA on hypothalamic-pituitary-adrenal axis, inflammation, and neuroactive mediators may be partly moderated through gut microbiome. Consideration of the gut microbiome and gut-brain communication, when evaluating the efficacy of DHA, may provide new insights in better understanding the mechanisms of DHA and impart advantages to future development of nutritional therapy based on the nutrient-microbiome interaction., Competing Interests: Author Declarations The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The gut-brain axis plays an important role in mental health. The intestinal epithelial surface is colonized by billions of commensal and transitory bacteria, known as the Gut Microbiota (GM). However, potential pathogens continuously stimulate intestinal immunity when they find the place. The last two decades have witnessed several studies revealing intestinal bacteria as a key factor in the health-disease balance of the gut, as well as disease-emergent in other parts of the body. Various neurological processes, such as cognition, learning, and memory, could be affected by dysbiosis in GM. Additionally, the aging process and longevity are related to systemic inflammation caused by dysbiosis. Commensal GM affects brain development, behavior, and healthy aging suggesting that building changes in GM might be a potential therapeutic method. The innovation in GM dysbiosis is intervention by Fecal Microbiota Transplantation (FMT), which has been confirmed as a therapy for recurrent Clostridium difficile infections and is promising for other clinical disorders, such as Parkinson's disease, Multiple Sclerosis (MS), Alzheimer's disease, and depression. Additionally, FMT may be possible to promote healthy aging, and extend longevity. This review aims to connect dysbiosis, neurological disorders, and aging and the potential of FMT as a therapeutic strategy to treat these disorders, and to enhance the quality of life in the elderly., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Our investigations on GABA-enriched tea and the reduction of stress in a student cohort have shown that more than just GABA may be involved. The effects of other constituents that are changed in the enrichment process are likely to be important. We have concentrated on GABA as well as the major tea flavonoid, epigallocatechin gallate. While this flavonoid is known to get to the brain on oral administration, it is far from clear that GABA does the same. GABA may act primarily on the gut and influence brain function via the gut-brain axis and the gut microbiome. In addition, there may be a microbiome in the brain that has a role. The situation is complex and not clearly understood. Mixtures of bioactive compounds are always difficult to investigate, but even the precise mechanisms of how pure oral GABA acts as a neuro-nutraceutical is unclear., Competing Interests: Declaration of competing interest We have no conflicts of interest to declare, financial or otherwise., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent research has illuminated the profound bidirectional communication between the gastrointestinal tract and the brain, furthering our understanding of neurological ailments facilitating possible therapeutic strategies. Technological advancements in high-throughput sequencing and multi-omics have unveiled significant alterations in gut microbiota and their metabolites in various neurological disorders. This review provides a thorough analysis of the role of microbiome-gut-brain axis in neurodegenerative disease pathology, linking it to reduced age-associated proteostasis. We discuss evidences that substantiate the existence of a gut-brain cross talk ranging from early clinical accounts of James Parkinson to Braak's hypothesis. In addition to understanding of microbes, the review particularly entails specific metabolites which are altered in neurodegenerative diseases. The regulatory effects of microbial metabolites on protein clearance mechanisms, proposing their potential therapeutic implications, are also discussed. By integrating this information, we advocate for a combinatory therapeutic strategy that targets early intervention, aiming to restore proteostasis and ameliorate disease progression. This approach not only provides a new perspective on the pathogenesis of neurodegenerative diseases but also highlights innovative strategies to combat the increasing burden of these age-related disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest No conflict of interest exists in relation to the submission of this manuscript, and the manuscript has been approved by all the authors for publication. I would like to declare on behalf of myself and my co-authors that the work described is original research that has not been published previously and is not under consideration for publication elsewhere, either in whole or in part. All the listed authors have approved the enclosed manuscript. Figs. 1-4 were created by Figdraw (www.figdraw.com)., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events., Purpose: The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review., (© 2024 John Wiley & Sons Ltd.)

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders., (© 2024. The Author(s).)

Various roles of intestinal flora in the gut-brain axis response pathway have received enormous attention because of their unique position in intestinal flora-derived metabolites regulating hormones, inducing appetite, and modulating energy metabolism. Reward pathways in the brain play a crucial role in gut-brain communications, but the mechanisms have not been methodically understood. This review outlined the mechanisms by which leptin, ghrelin, and insulin are influenced by intestinal flora-derived metabolites to regulate appetite and body weight, focused on the significance of the paraventricular nucleus and ventromedial prefrontal cortex in food reward. The vagus nerve and mitochondria are essential pathways of the intestinal flora involved in the modulation of neurotransmitters, neural signaling, and neurotransmission in gut-brain communications. The dynamic response to nutrient intake and changes in the characteristics of feeding activity requires the participation of the vagus nerve to transmit messages to be completed. SCFAs, Bas, BCAAs, and induced hormones mediate the sensory information and reward signaling of the host in the complex regulatory mechanism of food selection, and the composition of the intestinal flora significantly impacts this process. Food reward in the process of obesity based on gut-brain communications expands new ideas for the prevention and treatment of obesity.