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Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology. Methods: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD. Results: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including ß-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance. Conclusion: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines. [ABSTRACT FROM AUTHOR]

• Three different MSCs have varied therapeutic effects on AD model mice. • The gut microbiota dysbiosis of AD mice could be partially recovered after MSC treatment, antibiotic diminished the therapeutic impacts of MSCs. • MSCs treatment affected the bile acids related microbiota and metabolites. • Both MSCs and bile acids mediate the therapeutic outcomes in AD mice through MGBA. The intricacy and multifaceted nature of Alzheimer's disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types—derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)—in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5 × FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5 × FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA. [ABSTRACT FROM AUTHOR]

Abstract Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

This review summarizes the relationship between diet, the gut microbiome, and migraine. Key findings reveal that certain dietary factors, such as caffeine and alcohol, can trigger migraine, while nutrients like magnesium and riboflavin may help alleviate migraine symptoms. The gut microbiome, through its influence on neuroinflammation (e.g., vagus nerve and cytokines), gut–brain signaling (e.g., gamma-aminobutyric acid), and metabolic function (e.g., short-chain fatty acids), plays a crucial role in migraine susceptibility. Migraine can also alter eating behaviors, leading to poor nutritional choices and further exacerbating the condition. Individual variability in diet and microbiome composition highlights the need for personalized dietary and prebiotic interventions. Epidemiological and clinical data support the effectiveness of tailored nutritional approaches, such as elimination diets and the inclusion of beneficial nutrients, in managing migraine. More work is needed to confirm the role of prebiotics, probiotics, and potentially fecal microbiome translation in the management of migraine. Future research should focus on large-scale studies to elucidate the underlying mechanisms of bidirectional interaction between diet and migraine and develop evidence-based clinical guidelines. Integrating dietary management, gut health optimization, and lifestyle modifications can potentially offer a holistic approach to reducing migraine frequency and severity, ultimately improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

The traditional neuron-centric view of the central nervous system (CNS) is shifting toward recognizing the importance of communication between the neurons and the network of glial cells. This shift is leading to a more comprehensive understanding of how glial cells contribute to CNS function. Alongside this shift, recent discoveries have illuminated the significant role of the human microbiome, comprising trillions of microorganisms, mirroring the number of human cells in an individual. This paper delves into the multifaceted functions of neuroglia, or glial cells, which extend far beyond their traditional roles of supporting and protecting neurons. Neuroglia modulate synaptic activity, insulate axons, support neurogenesis and synaptic plasticity, respond to injury and inflammation, and engage in phagocytosis. Meanwhile, the microbiome, long overlooked, emerges as a crucial player in brain functionality akin to glial cells. This review aims to underscore the importance of the interaction between glial cells and resident microorganisms in shaping the development and function of the human brain, a concept that has been less studied. Through a comprehensive examination of existing literature, we discuss the mechanisms by which glial cells interface with the microbiome, offering insights into the contribution of this relationship to neural homeostasis and health. Furthermore, we discuss the implications of dysbiosis within this interaction, highlighting its potential contribution to neurological disorders and paving the way for novel therapeutic interventions targeting both glial cells and the microbiome. [ABSTRACT FROM AUTHOR]

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats. [ABSTRACT FROM AUTHOR]

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

The traditional neuron-centric view of the central nervous system (CNS) is shifting toward recognizing the importance of communication between the neurons and the network of glial cells. This shift is leading to a more comprehensive understanding of how glial cells contribute to CNS function. Alongside this shift, recent discoveries have illuminated the significant role of the human microbiome, comprising trillions of microorganisms, mirroring the number of human cells in an individual. This paper delves into the multifaceted functions of neuroglia, or glial cells, which extend far beyond their traditional roles of supporting and protecting neurons. Neuroglia modulate synaptic activity, insulate axons, support neurogenesis and synaptic plasticity, respond to injury and inflammation, and engage in phagocytosis. Meanwhile, the microbiome, long overlooked, emerges as a crucial player in brain functionality akin to glial cells. This review aims to underscore the importance of the interaction between glial cells and resident microorganisms in shaping the development and function of the human brain, a concept that has been less studied. Through a comprehensive examination of existing literature, we discuss the mechanisms by which glial cells interface with the microbiome, offering insights into the contribution of this relationship to neural homeostasis and health. Furthermore, we discuss the implications of dysbiosis within this interaction, highlighting its potential contribution to neurological disorders and paving the way for novel therapeutic interventions targeting both glial cells and the microbiome.

Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and neurodegenerative disorders. Here, we conduct a systematic review of gut microbiome assessments on infants (both healthy and with conditions that affect brain development) during the first thousand days of life, associated with neurodevelopmental outcomes, with the aim of investigating key microbiome players and mechanisms through which the gut microbiome affects the brain. Bacteroides and Bifidobacterium were associated with non-social fear behavior, duration of orientation, cognitive and motricity development, and neurotypical brain development. Lachnospiraceae, Streptococcus, and Faecalibacterium showed variable levels of influence on behavior and brain development. Few studies described mechanistic insights related to NAD salvage, aspartate and asparagine biosynthesis, methanogenesis, pathways involved in bile acid transformation, short-chain fatty acids production, and microbial virulence genes. Further studies associating species to gene pathways and robustness in data analysis and integration are required to elucidate the functional mechanisms underlying the role of microbiome–gut–brain axis in early brain development. [ABSTRACT FROM AUTHOR]

The gut microbiome is emerging as an important factor in signaling along the gut-brain axis. The intimate physiological connection between the gut and the brain allows perturbations in the microbiome to be directly transmitted to the central nervous system and thereby contribute to psychiatric and neurological diseases. Common microbiome perturbations result from the ingestion of xenobiotic compounds including pharmaceuticals such as psychotropic drugs. In recent years, a variety of interactions between these drug classes and the gut microbiome have been reported, ranging from direct inhibitory effects on gut bacteria to microbiome-mediated drug degradation or sequestration. Consequently, the microbiome may play a critical role in influencing the intensity, duration, and onset of therapeutic effects, as well as in influencing the side effects that patients may experience. Furthermore, because the composition of the microbiome varies from person to person, the microbiome may contribute to the frequently observed interpersonal differences in the response to these drugs. In this review, we first summarize the known interactions between xenobiotics and the gut microbiome. Then, for psychopharmaceuticals, we address the question of whether these interactions with gut bacteria are irrelevant for the host (i.e., merely confounding factors in metagenomic analyses) or whether they may even have therapeutic or adverse effects. [ABSTRACT FROM AUTHOR]

Background & Aims: Mounting evidence suggests the gastrointestinal microbiome is a determinant of peripheral immunity and central neurodegeneration, but the local disease mechanisms remain unknown. Given its potential relevance for early diagnosis and therapeutic intervention, we set out to map the pathogenic changes induced by bacterial amyloids in the gastrointestinal tract and its enteric nervous system. Methods: To examine the early response, we challenged primary murine myenteric networks with curli, the prototypical bacterial amyloid, and performed shotgun RNA sequencing and multiplex enzyme-linked immunosorbent assay. Using enteric neurosphere-derived glial and neuronal cell cultures, as well as in vivo curli injections into the colon wall, we further scrutinized curli-induced pathogenic pathways. Results: Curli induced a proinflammatory response, with strong up-regulation of Saa3 and the secretion of several cytokines. This proinflammatory state was induced primarily in enteric glia, was accompanied by increased levels of DNA damage and replication, and triggered the influx of immune cells in vivo. The addition of recombinant Serum Amyloid A3 (SAA3) was sufficient to recapitulate this specific proinflammatory phenotype while Saa3 knock-out attenuated curli-induced DNA damage and replication. Similar to curli, recombinant SAA3 caused a strong up-regulation of Saa3 transcripts, illustrating its self-amplifying potential . Since colonization of curli-producing Salmonella and dextran sulfate sodium–induced colitis triggered a significant increase in Saa3 transcripts as well, we assume SAA3plays a central role in enteric dysfunction. Inhibition of dual leucine zipper kinase, an upstream regulator of the c-Jun N-terminal kinase pathway responsible for SAA3 production, attenuated curli- and recombinant SAA3-induced Saa3 up-regulation, DNA damage, and replication in enteric glia. Conclusions: Our results position SAA3 as an important mediator of gastrointestinal vulnerability to bacterial-derived amyloids and demonstrate the potential of dual leucine zipper kinase inhibition to dampen enteric pathology.

AbstractContext Sinisan (SNS) has been used to treat psychosomatic diseases of the digestive system. But little is known about how SNS affects water immersion restraint stress (WIRS).Objective To study the effects of SNS on colonic tissue injury in the WIRS model.Materials and methods Forty-eight Kunming (KM) mice were randomized into 6 groups (n = 8): The control and WIRS groups receiving deionized water; the SNS low-dose (SL, 3.12 g/kg/d), SNS middle-dose (SM, 6.24 g/kg/d), SNS high-dose (SH, 12.48 g/kg/d), and diazepam (DZ, 5 mg/kg/d) groups; each with two daily administrations for 5 consecutive days. The 5 treatment groups were subjected to WIRS for 24 h on day 6. The effects of SNS on colon tissue injury caused by WIRS were assessed by changes in colon histology, inflammatory cytokines, brain-gut peptides, and tight junction (TJ) proteins levels. 16S rRNA gene sequencing was used to detect the regulation of the gut microbiota.Results SNS pretreatment significantly reduced TNF-α (0.75- to 0.81-fold), IL-6 (0.77-fold), and IFN-γ (0.69-fold) levels; and increased TJ proteins levels, such as ZO-1 (4.06- to 5.27-fold), claudin-1 (3.33- to 5.14-fold), and occludin (6.46- to 11.82-fold). However, there was no significant difference between the levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the control and WIRS groups. SNS regulated the composition of gut microbiota in WIRS mice.Conclusion The positive effects of SNS on WIRS could provide a theoretical basis to treat stress-related gastrointestinal disorders.

Background and objective: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice. Methods: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3  weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30  min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively. Results: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ETgroup mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice. Conclusion: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET. [ABSTRACT FROM AUTHOR]

Sinisan (SNS) has been used to treat psychosomatic diseases of the digestive system. But little is known about how SNS affects water immersion restraint stress (WIRS). To study the effects of SNS on colonic tissue injury in the WIRS model. Forty-eight Kunming (KM) mice were randomized into 6 groups (n = 8): The control and WIRS groups receiving deionized water; the SNS low-dose (SL, 3.12 g/kg/d), SNS middle-dose (SM, 6.24 g/kg/d), SNS high-dose (SH, 12.48 g/kg/d), and diazepam (DZ, 5 mg/kg/d) groups; each with two daily administrations for 5 consecutive days. The 5 treatment groups were subjected to WIRS for 24 h on day 6. The effects of SNS on colon tissue injury caused by WIRS were assessed by changes in colon histology, inflammatory cytokines, brain-gut peptides, and tight junction (TJ) proteins levels. 16S rRNA gene sequencing was used to detect the regulation of the gut microbiota. SNS pretreatment significantly reduced TNF-α (0.75- to 0.81-fold), IL-6 (0.77-fold), and IFN-γ (0.69-fold) levels; and increased TJ proteins levels, such as ZO-1 (4.06- to 5.27-fold), claudin-1 (3.33- to 5.14-fold), and occludin (6.46- to 11.82-fold). However, there was no significant difference between the levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the control and WIRS groups. SNS regulated the composition of gut microbiota in WIRS mice. The positive effects of SNS on WIRS could provide a theoretical basis to treat stress-related gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

An increasing number of studies indicate that the microbiota-gut-brain axis is an important pathway involved in the onset and progression of depression. The responses of the organism (or its microorganisms) to external cues cannot be separated from a key intermediate element: their metabolites. In recent years, with the rapid development of metabolomics, an increasing amount of metabolites has been detected and studied, especially the gut metabolites. Nevertheless, the increasing amount of metabolites described has not been reflected in a better understanding of their functions and metabolic pathways. Moreover, our knowledge of the biological interactions among metabolites is also incomplete, which limits further studies on the connections between the microbial-entero-brain axis and depression. This paper summarizes the current knowledge on depression-related metabolites and their involvement in the onset and progression of this disease. More importantly, this paper summarized metabolites from the intestine, and defined them as enterogenic metabolites, to further clarify the function of intestinal metabolites and their biochemical cross-talk, providing theoretical support and new research directions for the prevention and treatment of depression. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterised by both motor and non-motor symptoms. While most PD medications currently available can improve motor symptoms, there is currently no treatment available to halt or slow down the progression of the disease. Recently, there has been increasing focus on environmental factors in the pathophysiology of PD and their possible neuroprotective effects. According to Braak’s hypothesis, an unknown pathogen in the gastrointestinal tract may initiate the production of pathogenic α synuclein, which would subsequently spread to the central nervous system. The microbiome-gut-brain axis may be implicated in this process, whereas nutrition can be one of the modifiable regulatory variables. A variety of foods and nutrients have been suggested as either risk or protective factors based on biological theories. Although epidemiological and experimental studies in animal models have shown their neuroprotective properties, their effectiveness was not confirmed in clinical trials. However, daily food intake comprises many nutrients that can interact and produce either a synergistic or antagonistic effect on the human body. Therefore, dietary patterns that include a certain set of nutrients have recently gained increased interest as potential modifiers of disease progression and alleviators of symptoms. This article reviews the current literature on the role of different nutritional factors and diets in the pathogenesis of PD and their possible neuroprotective and symptomatic effects.

Emerging evidence supports the gut microbiota and the brain communication in general health. This axis may affect behavior through modulating neurotransmission, and thereby involve in the pathogenesis and/or progression of different neuropsychiatric disorders such as depression. Brain-derived neurotrophic factor and cAMP response element-binding protein known as CREB/BDNF pathway plays have critical functions in the pathogenesis of depression as the same of mechanisms related to antidepressants. However, the putative causal significance of the CREB/BDNF signaling cascade in the gut-brain axis in depression remains unknown. Also interventions such as probiotics supplementation and exercise can influence microbiome also improve bidirectional communication of gut and brain. In this review we aim to explain the BDNF/CREB signaling pathway and gut microbiota dysfunction and then evaluate the potential role of probiotics, prebiotics, and exercise as a therapeutic target in the gut microbiota dysfunction induced depression. The current narrative review will specifically focus on the impact of exercise and diet on the intestinal microbiota component, as well as the effect that these therapies may have on the microbiota to alleviate depressive symptoms. Finally, we look at how BDNF/CREB signaling pathway may exert distinct effects on depression and gut microbiota dysfunction.

Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis, which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome.

This review summarizes the relationship between diet, the gut microbiome, and migraine. Key findings reveal that certain dietary factors, such as caffeine and alcohol, can trigger migraine, while nutrients like magnesium and riboflavin may help alleviate migraine symptoms. The gut microbiome, through its influence on neuroinflammation (e.g., vagus nerve and cytokines), gut–brain signaling (e.g., gamma-aminobutyric acid), and metabolic function (e.g., short-chain fatty acids), plays a crucial role in migraine susceptibility. Migraine can also alter eating behaviors, leading to poor nutritional choices and further exacerbating the condition. Individual variability in diet and microbiome composition highlights the need for personalized dietary and prebiotic interventions. Epidemiological and clinical data support the effectiveness of tailored nutritional approaches, such as elimination diets and the inclusion of beneficial nutrients, in managing migraine. More work is needed to confirm the role of prebiotics, probiotics, and potentially fecal microbiome translation in the management of migraine. Future research should focus on large-scale studies to elucidate the underlying mechanisms of bidirectional interaction between diet and migraine and develop evidence-based clinical guidelines. Integrating dietary management, gut health optimization, and lifestyle modifications can potentially offer a holistic approach to reducing migraine frequency and severity, ultimately improving patient outcomes and quality of life.

The microbiome-gut-brain axis (MGBA) plays a critical role in schizophrenia (SZ). However, the underlying mechanisms of the interactions among the gut microbiome, brain networks, and symptom severity in SZ patients remain largely unknown. Fecal samples, structural and functional magnetic resonance imaging (MRI) data, and Positive and Negative Syndrome Scale (PANSS) scores were collected from 38 SZ patients and 38 normal controls, respectively. The data of 16S rRNA gene sequencing were used to analyze the abundance of gut microbiome and the analysis of human brain networks was applied to compute the nodal properties of 90 brain regions. A total of 1,691,280 mediation models were constructed based on 261 gut bacterial, 810 nodal properties, and 4 PANSS scores in SZ patients. A strong correlation between the gut microbiome and brain networks (r = 0.89, false discovery rate (FDR) -corrected p

ABSTRACTGenetic variants are traditionally known to shape the susceptibility to neuropsychiatric disorders. An increasing number of studies indicate that remodeling of the gut microbiome by genetic variance serves as a versatile regulator of gut-brain crosstalk and behavior. Evidence also emerges that certain behavioral symptoms are specifically attributed to gut microbial remodeling and gut-to-brain signals, which necessitates rethinking of neuropsychiatric disease etiology and treatment from a systems perspective of reciprocal gene-microbe interactions. Here, we present an emerging picture of how gut microbes and host genetics interactively shape complex psychiatric phenotypes. We illustrate the growing understanding of how the gut microbiome is shaped by genetic changes and its connection to behavioral outcome. We also discuss working strategies and open questions in translating associative gene-microbiome-behavior findings into causal links and novel targets for neurobehavioral disorders. Dual targeting of the genetic and microbial factors may expand the space of drug discovery for neuropsychiatric diseases.

Introduction and aim. Nowadays, almost 4% of people in the world suffer from depressive disorders, and the forecasts of further increase in incidence are alarming. The disease is debilitating and can lead to suicide, and available treatments are still imperfect. The aim of the study was to review the literature and present the potential role of the gut microbiota in the development of depression and to consider the use of prebiotics and probiotics as one of the therapeutic options in this disease. Material and methods. Review of articles published on PubMed since 2015. Analysis of the literature. The available reports point to a relationship between disturbances in the composition of the intestinal flora and the development of depressive disorders. In addition, more and more studies indicate the benefits of the influence on mood and clinical improvement, observed when using psychobiotics as an adjuvant treatment of depression, as well as monotherapy. Conclusion. Further research is needed in this area, especially in humans, to gain a deeper understanding of the role of the gut microbiota in depression and the promising use of psychobiotics for its treatment. [ABSTRACT FROM AUTHOR]

Background: Prenatal antibiotic exposure induces changes in the maternal microbiome, which could influence the development of the infant's microbiome–gut–brain axis. Objectives: We assessed whether prenatal antibiotic exposure is associated with an increased risk of autism spectrum disorder (ASD) in offspring born at term. Methods: This population‐based retrospective cohort study included everyone who delivered a live singleton‐term infant in British Columbia, Canada between April 2000 and December 2014. Exposure was defined as filling antibiotic prescriptions during pregnancy. The outcome was an ASD diagnosis from the British Columbia Autism Assessment Network, with a follow‐up to December 2016. To examine the association among pregnant individuals treated for the same indication, we studied a sub‐cohort diagnosed with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (HR). The analysis was stratified by sex, trimester, cumulative duration of exposure, class of antibiotic, and mode of delivery. We ran a conditional logistic regression of discordant sibling pairs to control for unmeasured environmental and genetic confounding. Results: Of the 569,953 children included in the cohort, 8729 were diagnosed with ASD (1.5%) and 169,922 were exposed to prenatal antibiotics (29.8%). Prenatal antibiotic exposure was associated with an increased risk of ASD (HR 1.10, 95% confidence interval [CI] 1.05, 1.15), particularly for exposure during the first and second trimesters (HR 1.11, 95% CI 1.04, 1.18 and HR 1.09, 95% CI 1.03, 1.16, respectively), and exposure lasting ≥15 days (HR 1.13, 95% CI 1.04, 1.23). No sex differences were observed. The association was attenuated in the sibling analysis (adjusted odds ratio 1.04, 95% CI 0.92, 1.17). Conclusions: Prenatal antibiotic exposure was associated with a small increase in the risk of ASD in offspring. Given the possibility of residual confounding, these results should not influence clinical decisions regarding antibiotic use during pregnancy. [ABSTRACT FROM AUTHOR]

The gut–brain axis refers to a bidirectional communication pathway linking the gastrointestinal system to the central nervous system. The hardware of this multifaceted pathway takes many forms, at once structural (neurons, microglia, intestinal epithelial cell barrier), chemical (neurotransmitters, enteroendocrine hormones, bacterial metabolites), and cellular (immune signaling, inflammatory pathways). The gut–brain axis is exquisitely influenced by our environment, diet, and behaviors. Here, we will describe recent progress in understanding the gut–brain axis in neurological disease, using Parkinson's disease as a guide. We will see that each component of the gut–brain axis is heavily mediated by intestinal microbiota and learn how gut–brain communication can go awry in microbial dysbiosis. [ABSTRACT FROM AUTHOR]

Abstract Background Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management. Methods A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months. Discussion The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis.

Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and neurodegenerative disorders. Here, we conduct a systematic review of gut microbiome assessments on infants (both healthy and with conditions that affect brain development) during the first thousand days of life, associated with neurodevelopmental outcomes, with the aim of investigating key microbiome players and mechanisms through which the gut microbiome affects the brain. Bacteroides and Bifidobacterium were associated with non-social fear behavior, duration of orientation, cognitive and motricity development, and neurotypical brain development. Lachnospiraceae, Streptococcus, and Faecalibacterium showed variable levels of influence on behavior and brain development. Few studies described mechanistic insights related to NAD salvage, aspartate and asparagine biosynthesis, methanogenesis, pathways involved in bile acid transformation, short-chain fatty acids production, and microbial virulence genes. Further studies associating species to gene pathways and robustness in data analysis and integration are required to elucidate the functional mechanisms underlying the role of microbiome–gut–brain axis in early brain development.

ABSTRACT: Feather pecking (FP) is a multifactorial abnormal behavior in laying hens where they display harmful pecks in conspecifics. FP has been associated with the altered functioning of the microbiome-gut-brain axis affecting host emotions and social behavior. The altered levels of serotonin (5-HT), a key monoaminergic neurotransmitter at both terminals of the gut-brain axis, affect the development of abnormal behavior, such as FP in laying hens. However, the underlying mechanism involving reciprocal interactions along the microbiota-gut-brain axis, particularly about the metabolism of 5-HT, remains unclear in FP phenotypes. This study examined the microbiota diversity, intestinal microbial metabolites, inflammatory responses, and 5-HT metabolism in divergently selected high (HFP; n = 8) and low (LFP; n = 8) FP hens to investigate the possible interconnections between FP behavior and the examined parameters. The 16S rRNA analysis revealed that compared to LFP birds, the gut microbiota of HFP birds exhibited a decrease in the abundance of phylum Firmicutes and genera Lactobacillus, while an increase in the abundance of phylum Proteobacteria and genera Escherichia Shigella and Desulfovibrio. Furthermore, the intestinal differential metabolites associated with FP phenotypes were mainly enriched in the tryptophan metabolic pathway. HFP birds had higher tryptophan metabolites and possibly a more responsive immune system compared to the LFP birds. This was indirectly supported by altered TNF-α levels in the serum and expression of inflammatory factor in the gut and brain. Moreover, HFP birds had lower serum levels of tryptophan and 5-HT compared to LFP birds, which was consistent with the downregulation of 5-HT metabolism-related genes in the brain of HFP birds. The correlation analysis revealed that genera Lactobacillus and Desulfovibrio were associated with differences in intestinal metabolites, 5-HT metabolism, and inflammatory response between the LFP and HFP birds. In conclusion, differences in the cecal microbiota profile, immune response and 5-HT metabolism drive FP phenotypes, which could be associated with the gut abundance of genera Lactobacillus and Desulfovibrio.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome–gut–brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function and microbiota metabolites in ASD. However, a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity and the microbiome–gut–brain axis in the development of autistic symptoms severity and a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via the microbiome–gut–brain axis in a feedback circuit. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterised by both motor and non-motor symptoms. While most PD medications currently available can improve motor symptoms, there is currently no treatment available to halt or slow down the progression of the disease. Recently, there has been increasing focus on environmental factors in the pathophysiology of PD and their possible neuroprotective effects. According to Braak’s hypothesis, an unknown pathogen in the gastrointes tinal tract may initiate the production of pathogenic α synuclein, which would subsequently spread to the central nervous system. The microbiome-gut-brain axis may be implicated in this process, whereas nutrition can be one of the modifiable regulatory variables. A variety of foods and nutrients have been suggested as either risk or protective factors based on biological theories. Although epidemiological and experimental studies in animal models have shown their neuroprotective properties, their effectiveness was not confirmed in clinical trials. However, daily food intake comprises many nutrients that can interact and produce either a synergistic or antagonistic effect on the human body. Therefore, dietary patterns that include a certain set of nutrients have recently gained increased interest as potential modifiers of disease progression and alleviators of symptoms. This article reviews the current literature on the role of different nutritional factors and diets in the pathogenesis of PD and their possible neuroprotective and symptomatic effects. [ABSTRACT FROM AUTHOR]

The relationship between the microbiota profile and exposure to stress is not well understood. Therefore, we used a rat model of unpredictable chronic mild stress (UCMS) to investigate this relationship. Depressive-like behaviors were measured in Female Sprague Dawley rats using the sucrose preference test and the Porsolt swim test. Anxiety-like behaviors were measured with the light–dark box test. Fecal corticosterone, cecal microbiota (composition and organic acids), plasma gut permeability (lipopolysaccharide-binding protein, LBP) and plasma inflammation (12 cytokines) markers were measured. Atypical behaviors were observed in female rats following UCMS, but no depressive-like behaviors were observed. Circulating concentrations of cytokines granulocyte-macrophage colony-stimulating factor and cytokine-induced neutrophil chemoattractant 1 were higher in UCMS-exposed female rats; plasma LBP and cecal organic acid levels remained unchanged. Our results reflect a resilient and adaptive phenotype for female SD rats. The relative abundance of taxa from the Clostridiales order and Desulfovibrionaceae family did, however, correlate both positively and negatively with anxiety-like behaviors and plasma cytokine concentrations, regardless of UCMS exposure, supporting the brain-to-gut influence of mild anxiety with a microbiota profile that may involve inflammatory pathways. [ABSTRACT FROM AUTHOR]

Introduction: The barrier function of the gut is important for many organs and systems, including the brain. If gut permeability increases, bacterial fragments may enter the circulation, giving rise to increased systemic inflammation. Increases in bacterial translocation are reflected in higher values of blood markers, including lipopolysaccharide binding protein (LBP) and soluble cluster of differentiation 14 (sCD14). Some pioneer studies showed a negative association between bacterial translocation markers and brain volumes, but this association remains scarcely investigated. We investigate the effect of bacterial translocation on brain volumes and cognition in both healthy controls and patients with a schizophrenia spectrum disorder (SSD). Materials and methods: Healthy controls (n = 39) and SSD patients (n = 72) underwent an MRI‐scan, venipuncture and cognition assessments. We investigated associations between LBP and sCD14 and brain volumes (intracranial volume, total brain volume, and hippocampal volume) using linear regression. We then associated LBP and sCD14 to cognitive function using a mediation analysis, with intracranial volume as mediator. Results: Healthy controls showed a negative association between hippocampal volume and LBP (b = –0.11, p =.04), and intracranial volume and sCD14 (b = –0.25, p =.07). Both markers were indirectly associated with lower cognitive functioning in healthy controls (LBP: b = –0.071, p =.028; sCD14: b = –0.213, p =.052), mediated by low intracranial volume. In the SSD patients, these associations were markedly less present. Conclusion: These findings extend earlier studies suggesting that increased bacterial translocation may negatively affect brain volume, which indirectly impacts cognition, even in this young healthy group. If replicated, this finding stresses the importance of a healthy gut for the development and optimal functioning of the brain. Absence of these associations in the SSD group may indicate that other factors such as allostatic load, chronic medication use and interrupted educational carrier had larger impact and attenuated the relative contribution of bacterial translocation. [ABSTRACT FROM AUTHOR]

Recently, a large number of experimenters have found that the pathogenesis of Parkinson's disease may be related to the gut microbiome and proposed the microbiome-gut-brain axis. Studies have shown that Toll-like receptors, especially Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), are key mediators of gut homeostasis. In addition to their established role in innate immunity throughout the body, research is increasingly showing that the Tolllike receptor 2 and Toll-like receptor 4 signaling pathways shape the development and function of the gut and enteric nervous system. Notably, Toll-like receptor 2 and Toll-like receptor 4 are dysregulated in Parkinson's disease patients and may therefore be identified as the core of early gut dysfunction in Parkinson's disease. To better understand the contribution of Toll-like receptor 2 and Toll-like receptor 4 dysfunction in the gut to early α-synuclein aggregation, we discussed the structural function of Toll-like receptor 2 and Toll-like receptor 4 and signal transduction of Toll-like receptor 2 and Tolllike receptor 4 in Parkinson's disease by reviewing clinical, animal models, and in vitro studies. We also present a conceptual model of the pathogenesis of Parkinson's disease, in which microbial dysbiosis alters the gut barrier as well as the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways, ultimately leading to a positive feedback loop for chronic gut dysfunction, promoting α-synuclein aggregation in the gut and vagus nerve. [ABSTRACT FROM AUTHOR]

Being isolated from the peripheral system by the blood-brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) influences gastrointestinal and brain disorders such as Alzheimer's disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research. [ABSTRACT FROM AUTHOR]

The development of abnormal feather-pecking (FP) behavior, where laying hens display harmful pecks in conspecifics, is multifactorial and has been linked to the microbiota-gut-brain axis. Antibiotics affect the gut microbial composition, leading to gut-brain axis imbalance and behavior and physiology changes in many species. However, it is not clear whether intestinal dysbacteriosis can induce the development of damaging behavior, such as FP. The restorative effects of Lactobacillus rhamnosus LR-32 against intestinal dysbacteriosisinduced alternations need to be determined either. The current investigation aimed to induce intestinal dysbacteriosis in laying hens by supplementing their diet with the antibiotic lincomycin hydrochloride. The study revealed that antibiotic exposure resulted in decreased egg production performance and an increased tendency toward severe feather-pecking (SFP) behavior in laying hens. Moreover, intestinal and blood-brain barrier functions were impaired, and 5-HT metabolism was inhibited. However, treatment with Lactobacillus rhamnosus LR-32 following antibiotic exposure significantly alleviated the decline in egg production performance and reduced SFP behavior. Lactobacillus rhamnosus LR-32 supplementation restored the profile of the gut microbial community, and showed a strong positive effect by increasing the expression of tight junction proteins in the ileum and hypothalamus and promoting the expression of genes related to central 5-HT metabolism. The correlation analysis revealed that probiotic-enhanced bacteria were positively correlated, and probiotic-reduced bacteria were negatively correlated with tight junctionrelated gene expression, and 5-HT metabolism, and butyric acid levels. Overall, our findings indicate that dietary supplementation with Lactobacillus rhamnosus LR-32 can reduce antibiotic-induced FP in laying hens and is a promising treatment to improve the welfare of domestic birds. [ABSTRACT FROM AUTHOR]

Abstract Background Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer’s disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

Background: Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management. Methods: A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months. Discussion: The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation. [ABSTRACT FROM AUTHOR]

Approximately 400 million people work and live in high-altitude areas and suffer from memory dysfunction worldwide. Until now, the role of the intestinal flora in plateau-induced brain damage has rarely been reported. To address this, we investigated the effect of intestinal flora on spatial memory impairment induced by high altitudes based on the microbiome–gut–brain axis theory. C57BL/6 mice were divided into three groups: control, high-altitude (HA), and high-altitude antibiotic treatment (HAA) group. The HA and HAA groups were exposed to a low-pressure oxygen chamber that simulated an altitude of 4000 m above sea level (m. a. s.l.) for 14 days, with the air pressure in the chamber set at 60–65 kPa. The results showed that spatial memory dysfunction induced by the high-altitude environment was aggravated by antibiotic treatment, manifesting as lowered escape latency and hippocampal memory-related proteins (BDNF and PSD-95). 16 S rRNA sequencing showed a remarkable separation of the ileal microbiota among the three groups. Antibiotic treatment exacerbated the reduced richness and diversity of the ileal microbiota in mice in the HA group. Lactobacillaceae were the main target bacteria and were significantly reduced in the HA group, which was exacerbated by antibiotic treatment. Meanwhile, reduced intestinal permeability and ileal immune function in mice exposed high-altitude environment was also aggravated by antibiotic treatment, as indicated by the lowered tight junction proteins and IL-1β and IFN-γ levels. Furthermore, indicator species analysis and Netshift co-analysis revealed that Lactobacillaceae (ASV11) and Corynebacteriaceae (ASV78, ASV25, and ASV47) play important roles in high-altitude exposure-induced memory dysfunction. Interestingly, ASV78 was negatively correlated with IL-1β and IFN-γ levels, indicating that ASV78 may be induced by reduced ileal immune function, which mediates high-altitude environment exposure-induced memory dysfunction. This study provides evidence that the intestinal flora is effective in preventing brain dysfunction caused by exposure to high-altitude environments, suggesting a relationship between the microbiome–gut–brain axis and altitude exposure.

Abstract Introduction The barrier function of the gut is important for many organs and systems, including the brain. If gut permeability increases, bacterial fragments may enter the circulation, giving rise to increased systemic inflammation. Increases in bacterial translocation are reflected in higher values of blood markers, including lipopolysaccharide binding protein (LBP) and soluble cluster of differentiation 14 (sCD14). Some pioneer studies showed a negative association between bacterial translocation markers and brain volumes, but this association remains scarcely investigated. We investigate the effect of bacterial translocation on brain volumes and cognition in both healthy controls and patients with a schizophrenia spectrum disorder (SSD). Materials and methods Healthy controls (n = 39) and SSD patients (n = 72) underwent an MRI‐scan, venipuncture and cognition assessments. We investigated associations between LBP and sCD14 and brain volumes (intracranial volume, total brain volume, and hippocampal volume) using linear regression. We then associated LBP and sCD14 to cognitive function using a mediation analysis, with intracranial volume as mediator. Results Healthy controls showed a negative association between hippocampal volume and LBP (b = –0.11, p = .04), and intracranial volume and sCD14 (b = –0.25, p = .07). Both markers were indirectly associated with lower cognitive functioning in healthy controls (LBP: b = –0.071, p = .028; sCD14: b = –0.213, p = .052), mediated by low intracranial volume. In the SSD patients, these associations were markedly less present. Conclusion These findings extend earlier studies suggesting that increased bacterial translocation may negatively affect brain volume, which indirectly impacts cognition, even in this young healthy group. If replicated, this finding stresses the importance of a healthy gut for the development and optimal functioning of the brain. Absence of these associations in the SSD group may indicate that other factors such as allostatic load, chronic medication use and interrupted educational carrier had larger impact and attenuated the relative contribution of bacterial translocation.

Major depression disorder is more common among adolescents and is a primary reason for suicide in adolescents. Some antidepressants are ineffective and may possess side effects. Therefore, developing an adolescent antidepressant is the need of the hour. We designed the stress model of adolescent male mice induced by chronic unpredictable stress (CUS). The mice were treated using Tongxieyaofang neutral polysaccharide (TXYF-NP), Tongxieyaofang acidic polysaccharide (TXYF-AP), TXYF-AP + TXYF-NP and fructooligosaccharide + galactooligosaccharides to determine their body weight, behavior, and serum hormone levels. RT-qPCR was used to detect the gene expression of Crhr1, Nr3c1, and Nr3c2 in the hypothalamus and hippocampus and the gene expression of glutamic acid and γ-aminobutyric acid-related receptors in the hippocampus. RT-qPCR, Western blot, and ELISA detected tryptophan metabolism in the colon, serum, and hippocampus. 16s rDNA helped sequence colon microflora, and non-targeted metabolomics enabled the collection of metabolic profiles of colon microflora. In adolescent male mice, CUS induced depression-like behavior, hypothalamic–pituitary–adrenal axis hyperactivity, hippocampal tissue damage, abnormal expression of its related receptors, and dysregulation of tryptophan metabolism. The 16s rDNA and non-targeted metabolomics revealed that CUS led to colon microflora disorder and bile acid metabolism abnormality. Tongxieyaofang polysaccharide could improve the bacterial community and bile acid metabolism disorder by upregulating the relative abundance of Lactobacillus gasseri, Lachnospiraceae bacterium 28–4, Bacteroides and Ruminococcaceae UCG-014 while preventing CUS-induced changes. TXYF-P can inhibit depression-like behavior due to CUS by regulating colonic microflora and restoring bile acid metabolism disorder. Thus, based on the different comparisons, TXYF-NP possessed the best effect.

Abstract Background Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. Methods This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. Discussion Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. Trial registration German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

Background. According to the World Health Organization, about 50 million people worldwide suffer from epilepsy. Almost 1/3 of patients are diagnosed with drug-resistant epilepsy (DRE). There is a relationship between the intestinal microbiome (IM) and the central nervous system, which is carried out throughout life through a bidirectional dynamic network. There is evidence that IM changes in patients with DRE.Objective: to summarize the current literature data on the role of the microbiome-gut-brain axis in DRE, as well as to assess the value of changes in the composition of IM as a prognostic marker of the development of DRE.Material and methods. The authors conducted a search for publications in the electronic databases PubMed/MEDLINE and eLibrary, as well as Google Scholar search engine. The evaluation of the articles was carried out in accordance with the PRISMA recommendations. As a result of the search, 4,158 publications from PubMed/MEDLINE database, 173 publications from eLibrary, and 1,100 publications found with Google Scholar were extracted. After the selection procedure, 121 studies were included in the review.Results. The review provides convincing evidence of a correlation between IM and DRE. There were obvious differences in the composition of the intestinal microbiota in patients with epilepsy, depending on sensitivity to drugs. Dysbiosis of the intestinal microbiota can be corrected by exogenous interventions such as ketogenic diet, probiotic treatment and fecal microbiota transplantation, which subsequently leads to changes in neurochemical signaling in the brain and, consequently, to a decrease in epileptic activity.Conclusion. A ketogenic diet, probiotics and antibiotics may have some potential to influence epilepsy through the correction of dysbiosis of the intestinal microbiota, but the studies available to date do not provide an adequate level of evidence. Future clinical multicenter trials should use standardized protocols and a larger sample to provide more reliable evidence.In addition, further fundamental research is needed to elucidate potential mechanisms and therapeutic targets.

Background Intestinal microbiota homeostasis and the gut-brain axis are key players associated with host health and alterations in metabolic, inflammatory, and neurodegenerative disorders. Sepsis-associated encephalopathy (SAE), which is closely associated with bacterial translocation, is a common secondary organ dysfunction and an urgent, unsolved problem affecting patient quality of life. Our study examined the neuroprotective effects of the gut microbiome and short-chain fatty acid (SCFA) metabolites on SAE. Methods Male C57BL/6 mice were administered SCFAs in drinking water, then subjected to cecal ligation and puncture (CLP) surgery to induce SAE. 16S rRNA sequencing was used to investigate gut microbiome changes. The open field test (OFT) and Y-maze were performed to evaluate brain function. The permeability of the blood–brain barrier (BBB) was assessed by Evans blue (EB) staining. Hematoxylin and eosin (HE) staining was used to examine intestinal tissue morphology. The expression levels of tight junction (TJ) proteins and inflammatory cytokines was assessed by western blots and immunohistochemistry. In vitro, bEND.3 cells were incubated with SCFAs and then with lipopolysaccharide (LPS). Immunofluorescence was used to examine the expression of TJ proteins. Results The composition of the gut microbiota was altered in SAE mice; this change may be related to SCFA metabolism. SCFA treatment significantly alleviated behavioral dysfunction and neuroinflammation in SAE mice. SCFAs upregulated occludin and ZO-1 expression in the intestine and brain in SAE mice and LPS-treated cerebromicrovascular cells. Conclusions These findings suggested that disturbances in the gut microbiota and SCFA metabolites play key roles in SAE. SCFA supplementation could exert neuroprotective effects against SAE by preserving BBB integrity.

Background: Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods: We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer's disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results: We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions: Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development. [ABSTRACT FROM AUTHOR]

The relationship between social behaviour and the microbiome is known to be reciprocal. Research in wild animal populations, particularly in primate social groups, has revealed the role that social interactions play in microbial transmission, whilst studies in laboratory animals have demonstrated that the gut microbiome can affect multiple aspects of behaviour, including social behaviour. Here we explore behavioural variation in a non-captive animal population with respect to the abundance of specific bacterial genera. Social behaviour based on grooming interactions is assessed in a population of rhesus macaques (Macaca mulatta), and combined with gut microbiome data. We focus our analyses on microbiome genera previously linked to sociability and autistic behaviours in rodents and humans. We show in this macaque population that some of these genera are also related to an individual's propensity to engage in social interactions. Interestingly, we find that several of the genera positively related to sociability, such as Faecalibacterium, are well known for their beneficial effects on health and their anti-inflammatory properties. In contrast, the genus Streptococcus, which includes pathogenic species, is more abundant in less sociable macaques. Our results indicate that microorganisms whose abundance varies with individual social behaviour also have functional links to host immune status. Overall, these findings highlight the connections between social behaviour, microbiome composition, and health in an animal population. [ABSTRACT FROM AUTHOR]

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice. • The first exploration of the impact of traditional Chinese treatment method electroacupuncture on perioperative neurocognitive disorder, as well as whether the therapeutic effect of electroacupuncture is related to the gut microbiota. • By further utilizing the PND germ-free mouse fecal microbiota transplantation model, we aim to investigate whether the gut microbiota serves as an intermediate mediator in the effects of electroacupuncture on cognitive function. • We link PND, gut flora, and electroacupuncture and explore their relationship to each other. [ABSTRACT FROM AUTHOR]