Gut-brain Research Articles

Drug-Resistant Epilepsy and Gut-Brain Axis: an Overview of a New Strategy for Treatment.

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.

Trehalose: Neuroprotective Effects and Mechanisms-An Updated Review.

Trehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose's impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose's neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut-brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases.

Gut Microbiome in Alzheimer's Disease: from Mice to Humans.

Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. The gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.

The New Approach to the Gut-Brain Axis Research and Possible Implications for the Rethinking of the Addiction Problem

The New Approach to the Gut-Brain Axis Research and Possible Implications for the Rethinking of the Addiction Problem

Gut-brain axis in Drosophila aging.

Gut-brain axis in Drosophila aging.

Roles of the gut microbiota in human neurodevelopment and adult brain disorders

Growing evidence demonstrates the connection between gut microbiota, neurodevelopment, and adult brain function. Microbial colonization occurs before the maturation of neural systems and its association with brain development. The early microbiome interactions with the gut-brain axis evolved to stimulate cognitive activities. Gut dysbiosis can lead to impaired brain development, growth, and function. Docosahexaenoic acid (DHA) is critically required for brain structure and function, modulates gut microbiota, and impacts brain activity. This review explores how gut microbiota influences early brain development and adult functions, encompassing the modulation of neurotransmitter activity, neuroinflammation, and blood-brain barrier integrity. In addition, it highlights processes of how the gut microbiome affects fetal neurodevelopment and discusses adult brain disorders.

The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function

The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic–pituitary–adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.

Lifestyle and the Gut-Brain Axis Insights into Mental Health and Microbiome Interactions

Introduction: The intricate relationship between lifestyle factors and gut health has become a focus of recent research, emphasizing the significant role of the gut-brain axis (GBA) in regulating both physical and emotional well- being. Unhealthy lifestyle choices, including a diet high in ultra-processed foods, irregular sleep patterns, physical inactivity, and substance abuse, have been closely associated with gut dysbiosis, leading to gastrointestinal (GI) symptoms and mood disturbances such as anxiety and depression. The gut microbiota, through the production of neurotransmitters like serotonin and dopamine, as well as short-chain fatty acids (SCFAs), influences mood and mental health via the GBA. Maintaining a healthy lifestyle, characterized by balanced nutrition, regular physical activity, and good sleep quality, is critical in fostering a diverse and stable gut microbiome, which in turn supports emotional stability.  Aim: This review aims to examine the existing literature on the impact of lifestyle factors, such as diet, physical activity, sleep, smoking, alcohol consumption, and stress management, on gut health and emotional well-being. The goal is to highlight the importance of gut microbiota in mental health and the potential therapeutic strategies to enhance gut health for improved emotional outcomes.  Methodology: A comprehensive search of peer-reviewed journal articles was conducted using databases such as PubMed, Google Scholar, and Web of Science. Keywords like "lifestyle," "gut health," "emotional well-being," "dietary habits," "physical activity," "sleep patterns," and "gut-brain axis" were used to identify relevant studies. Inclusion criteria focused on human clinical trials and observational studies published within the last 16 years. Studies involving animal subjects, non-peer- reviewed articles, and outdated research were excluded.  Results: The literature shows that diets high in fiber and low in processed foods support a healthier gut microbiome, while high consumption of ultra-processed foods disrupts gut bacteria, leading to GI symptoms and mood disorders. Regular physical activity was found to enhance gut microbiota diversity, contributing to better emotional well-being. Conversely, poor sleep quality and chronic stress were linked to gut dysbiosis, which exacerbated mood disturbances. Smoking and excessive alcohol consumption further damaged gut health, contributing to mood dysregulation. Probiotic and prebiotic interventions, particularly synbiotics, were found to restore gut balance and improve both GI and mental health outcomes.  Conclusion: This review underscores the pivotal role of lifestyle choices in shaping gut health and emotional well-being. A balanced diet, regular exercise, sufficient sleep, and stress management are essential for maintaining a healthy gut microbiome, which, in turn, supports emotional stability. Therapeutic strategies involving prebiotics, probiotics, and synbiotics offer promising avenues for improving both gut health and mood. Addressing lifestyle factors and promoting gut health can potentially serve as an effective approach for enhancing overall well-being and preventing mood disorders.

Microplastics and human health: unveiling the gut microbiome disruption and chronic disease risks

Microplastics (MPs), defined as plastic particles smaller than 5 mm, are increasingly recognized as environmental contaminants with potential health risks. These emerge as breakdown products of larger plastics and are omnipresent in marine, freshwater, and terrestrial ecosystems. They are primarily composed of polymers such as polyethylene, polypropylene, polystyrene, and additives that enhance their performance. MPs also adsorb harmful environmental chemicals like persistent organic pollutants and heavy metals, posing risks to human and environmental health. Human exposure to MPs occurs mainly through ingestion and inhalation, with MPs detected in food products, water, and even the air. MPs have been shown to accumulate in the gastrointestinal tract, disrupting the gut microbiome, and causing dysbiosis-a harmful imbalance between beneficial and harmful bacteria. This disruption has been linked to various health issues, including gastrointestinal disorders, systemic inflammation, and chronic diseases. Furthermore, the gut-brain axis may be affected, with potential neuroinflammatory consequences. As research continues to unravel the health impacts of MP exposure, understanding the mechanisms of accumulation and the broader implications on human health is crucial. This review highlights the effects of MPs on human health, emphasizing their impact on the gut microbiome. We discuss the potential connections between MP exposure and cardiometabolic and inflammatory diseases, and disorders related to the Gut-Brain Axis. By synthesizing the latest research, this work sheds light on the silent yet pervasive threat posed by MPs and underscores the importance of further studies to understand their health impacts fully.

Microbiota and Autism: A Review on Oral and Gut Microbiome Analysis Through 16S rRNA Sequencing

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiologies, including genetic, environmental, and microbiological factors. In recent years, increasing attention has been given to the role of the gut microbiota in ASD. Emerging evidence suggests that gut microbiota dysbiosis may influence the central nervous system through the gut-brain axis, potentially impacting behavior and neurodevelopment. The use of 16S rRNA gene sequencing has become a pivotal tool in profiling the microbial communities associated with ASD, offering valuable insights into bacterial diversity, composition, and potential functional roles. This review aims to provide a comprehensive analysis of current findings on the relationship between the gut and oral microbiota with ASD, and a particular focus on studies utilizing 16S rRNA sequencing. We will explore how gut microbiome alterations may contribute to ASD pathophysiology, discuss the limitations of existing research, and propose future directions for the integration of microbiome analysis in ASD diagnostics and treatment strategies. These findings underscore the potential role of microbiota in modulating ASD symptoms. The data suggest that specific bacterial taxa are consistently altered in ASD, which may have implications for understanding the gut-brain axis and its influence on neurodevelopment.

Optimizing Lactiplantibacillus plantarum viability in the gastrointestinal tract and its impact on gut microbiota-brain axis through zein microencapsulation.

Evidence suggests that Lactiplantibacillus plantarum (LP) can positively influence gut microbiota, subsequently affecting brain function via the gut-brain axis. However, the oral administration of LP may subject it to damage from gastric acid. To address this issue, a microencapsulation system was developed to protect LP and enhance its viability in the gastrointestinal tract. In the study, zein-microencapsulated LP (MLP) was prepared using the phase separation method. We found that the optimal conditions to encapsulate LP (9logCFU/mL) were a zein concentration of 10mg/mL and a zein-to-bacteria mass ratio of 5:1. Scanning electron microscopy and dynamic light scattering analysis demonstrated that MLP exhibited a microstructure with an approximate diameter of 4µm. Findings also revealed that microencapsulation markedly improved the in vitro survival rate of LP compared to free cells and allowed for controlled release. Subsequent in vivo studies in mice showed that this encapsulation not only boosted the colonization of LP but also ameliorated the imbalance of gut microbiota associated with depression. An analysis of the intestinal microbiota in mice identified 13 genera that exhibited significant shifts in abundance due to the depressive states. The administration of MLP reversed these microbial changes, underscoring its therapeutic potential. Additionally, the study examined the expression of pro-inflammatory cytokines. The administrated MLP was found to reverse the inflammation in both the intestine and hippocampus of mice with depression. Behavioral assessments in mouse models corroborated the efficacy of MLP in preventing depression, positioning it as a promising daily supplement.

Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut–Brain Axis: Implications for Alzheimer’s and Parkinson’s Disease Pathogenesis

Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut–brain axis, with significant implications for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. H2S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H2S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H2S has a dual role or a Janus face, excessive H2S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer’s and Parkinson’s diseases, where the overproduction of H2S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H2S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H2S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer’s and Parkinson’s diseases, underscoring the critical role of the gut–brain axis in maintaining central nervous system health.

TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure

BackgroundObesity has become a global pandemic, marked by significant shifts in both the homeostatic and hedonic/reward aspects of food consumption. While the precise causes are still under investigation, recent studies have identified the role of gut microbes in dysregulating the reward system within the context of obesity. Unravelling these gut–brain connections is crucial for developing effective interventions against eating and metabolic disorders, particularly in the context of obesity. This study explores the causal role of LPS, as a key relay of microbiota component-induced neuroinflammation in the dysregulation of the reward system following exposure to high-fat diet (HFD).MethodsThrough a series of behavioural paradigms related to food-reward events and the use of pharmacological agents targeting the dopamine circuit, we investigated the mechanisms associated with the development of reward dysregulation during HFD-feeding in male mice. A Toll-like receptor 4 (TLR4) full knockout model and intraventricular lipopolysaccharide (LPS) diffusion at low doses, which mimics the obesity-associated neuroinflammatory phenotype, were used to investigate the causal roles of gut microbiota-derived components in neuroinflammation and reward dysregulation.ResultsOur study revealed that short term exposure to HFD (24 h) tended to affect food-seeking behaviour, and this effect became significant after 1 week of HFD. Moreover, we found that deletion of TLR4 induced a partial protection against HFD-induced neuroinflammation and reward dysregulation. Finally, chronic brain diffusion of LPS recapitulated, at least in part, HFD-induced molecular and behavioural dysfunctions within the reward system.ConclusionsThese findings highlight a link between the neuroinflammatory processes triggered by the gut microbiota components LPS and the dysregulation of the reward system during HFD-induced obesity through the TLR4 pathway, thus paving the way for future therapeutic approaches.Graphical abstract

The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract.

Visceral pain is a major clinical problem and one of the most common reasons patients with gastrointestinal disorders seek medical help. Peripheral sensory neurons that innervate the gut can detect noxious stimuli and send signals to the central nervous system that are perceived as pain. There is a bidirectional communication network between the gastrointestinal tract and the nervous system that mediates pain through the gut-brain axis. Sensory neurons detect mechanical and chemical stimuli within the intestinal tissues, and receive signals from immune cells, epithelial cells and the gut microbiota, which results in peripheral sensitization and visceral pain. This Review focuses on molecular communication between these non-neuronal cell types and neurons in visceral pain. These bidirectional interactions can be dysregulated during gastrointestinal diseases to exacerbate visceral pain. We outline the anatomical pathways involved in pain processing in the gut and how cell-cell communication is integrated into this gut-brain axis. Understanding how bidirectional communication between the gut and nervous system is altered during disease could provide new therapeutic targets for treating visceral pain.

The emerging roles of neuroactive components produced by gut microbiota.

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 1013 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. 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. 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.

Research progress of methamphetamine in brain-gut axis

Methamphetamine (METH) is an illegal psychostimulant that has been widely abused. Currently, METH abuse is a major health and social problem facing the world. To figure out the METH’s influence on the brain-gut axis, the relevant literature was searched through PubMed, CNKI, and other databases with keywords “methamphetamine”, “brain-gut axis”, “neurotoxicity”, “intestinal barrier”, “intestinal microbes". The selected literature is highly related to these keywords, with the latest 5 years as the threshold to ensure that the research contents keep pace with the times. By summarizing the relevant literature, it was found that METH could destroy the normal structure of the brain and intestine and affect their function, and also the release of some neurotransmitters or cytokines, damage the blood-brain barrier, intestinal barrier, disturb the intestinal microbes, and aggravate neurotoxic symptoms. METH affects both the brain and gut, causing a range of central nervous system and digestive diseases. Conclusively, this review summarizes the main mechanism of brain function, gut function, and brain-gut axis dysfunction induced by METH, so as to further understand the damaging effect and influence of METH and provide guidance for clinical practice.

Gut Microbiota and Neuroinflammation: An Interconnected Nexus of Health and Neurodegenerative Disease

The gut microbiota, a complex ecosystem of billions of microorganisms in the human digestive tract, plays a crucial role in maintaining health. Recent studies have highlighted a bidirectional communication pathway called the gut-brain axis between the gut and the brain. This communication is significantly influenced by gut microbiota and its interactions with the immune system, which can affect brain function and contribute to inflammation. This study aims to provide a comprehensive overview of the relationship between gut microbiota and neuroinflammation, focusing on the underlying mechanisms and implications for neurological disorders. A thorough literature review was conducted, examining the impact of gut microbiota on neuroinflammation, the mechanisms of this interaction, and potential therapeutic applications. The gut microbiota modulates neuroinflammation through various pathways, including producing short-chain fatty acids (SCFAs), modulating the immune system, and regulating the nervous system. Dysbiosis, characterized by an imbalance in gut microbiota composition, has been associated with an increased risk of neuroinflammation and various neurological conditions. Interventions such as probiotics, prebiotics, and fecal microbiota transplantation show promise in treating neuroinflammation. Understanding the pivotal role of gut microbiota in neuroinflammation is essential for developing novel strategies to prevent and manage neurological diseases. Further research is needed to elucidate the mechanisms involved, identify specific gut microbiota profiles associated with different neurological disorders, and optimize personalized therapies based on microbiome modulation.

GOS enhances BDNF-mediated mammary gland development in pubertal mice via the gut-brain axis

The “gut-brain axis” is involved in many physiological processes. However, its role in regulating mammary gland (MG) development remains unknown. In this study, we established the mice model of bilateral subdiaphragmatic vagotomy (Vago) to clarify the effects of “gut-brain axis” on MG development in pubertal mice. The results showed that Vago reduced the ratio of Lactobacillus and Bifidobacterium, neuronal excitability in the nucleus of solitary tract (NTS), and synthesis and secretion of BDNF, thereby slowing MG development. Transplanting the gut microbiota of Vago mice to recipient mice replicated these effects, and transplanting the gut microbiota of Control mice to Vago mice did not alleviate these effects. Galacto-Oligosaccharide (GOS), which up-regulates the ratio of Lactobacillus and Bifidobacterium, supplementation elevated NTS neuron excitability, synthesis and secretion of BDNF, and MG development, but Vago reversed these benefits. In conclusion, GOS enhances BDNF-mediated mammary gland development in pubertal mice via the “gut-brain axis”.

A review on gut microbiota and miRNA crosstalk: implications for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.

Brain injury in premature infants may be related to abnormal colonization of early gut microbiome.

Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16S rRNA technology. Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups. At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group. Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.