Gut-brain Research Articles

Anti-Inflammatory Effects of Hydrogen Sulfide in Axes Between Gut and Other Organs.

Significance: Hydrogen sulfide (H2S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) via reducing inflammation, inhibiting oxidative stress, and cell apoptosis. Recent Advances: Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H2S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. Critical Issues: We reviewed endogenous H2S biogenesis and the H2S-releasing donors, and revealed the anti-inflammatory effects of H2S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H2S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. Future Direction: The rate, location, and timing of H2S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H2S concentration. Moreover, more efficient H2S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. Antioxid. Redox Signal. 00, 000-000.

Mechanisms of microbiota-gut-brain axis communication in anxiety disorders

Anxiety disorders, prevalent mental health conditions, receive significant attention globally due to their intricate etiology and the suboptimal effectiveness of existing therapies. Research is increasingly recognizing that the genesis of anxiety involves not only neurochemical brain alterations but also changes in gut microbiota. The microbiota-gut-brain axis (MGBA), serving as a bidirectional communication pathway between the gut microbiota and the central nervous system (CNS), is at the forefront of novel approaches to deciphering the complex pathophysiology of anxiety disorders. This review scrutinizes the role and recent advancements in the MGBA concerning anxiety disorders through a review of the literature, emphasizing mechanisms via neural signals, endocrine pathways, and immune responses. The evidence robustly supports the critical influence of MGBA in both the development and progression of these disorders. Furthermore, this discussion explores potential therapeutic avenues stemming from these insights, alongside the challenges and issues present in this realm. Collectively, our findings aim to enhance understanding of the pathological mechanisms and foster improved preventative and therapeutic strategies for anxiety disorders.

Chemotherapy-Induced Neuropathy Affecting the Gastrointestinal Tract.

Cancer is a major global cause of morbidity and mortality. Survivorship is increasing, bringing new challenges. Cancer treatment, including chemotherapeutic drugs, immunotherapy, and radiotherapy, can have severe and impactful gastrointestinal side effects occurring shortly after treatment (acute toxicity) or persisting for years after treatment ends (late/chronic toxicity). The aim of this article is to review the neurotoxic effects of chemotherapy on the enteric nervous system (ENS) and the gut extrinsic innervation. These effects could contribute to the development of long-term gastrointestinal dysfunctions. Research, primarily conducted in animal models, indicates that antitumoral drugs can lead to chemotherapy-induced enteric neuropathy (CIEN). Studies, mainly performed in the myenteric plexus, show that CIEN is characterized by a reduced density of nerve cells and fibers, as well as an imbalanced representation of neuronal subpopulations or their markers, with enteric glial cells also affected. These alterations underlie changes in neuronal activity and gastrointestinal motor function. Although research on the submucosal plexus remains limited, evidence suggests that CIEN affects the entire ENS. Furthermore, scarce studies show that CIEN also occurs in humans. Moreover, emerging experimental data on chemotherapy-induced alterations in visceral sensitivity suggest that the extrinsic innervation of the gut is also affected, but this has received little attention thus far. Nevertheless, this could contribute to the development of chemotherapy-induced brain-gut axis (BGA) disorders in the long term. Cancer chemotherapy (and probably also immunotherapy and radiotherapy) seems to cause neuropathic effects on the intrinsic and extrinsic innervation of the gastrointestinal tract, with an important impact on gastrointestinal and BGA functions. This is a relatively neglected area deserving further investigation.

Research advances in gut microbes and autism spectrum disorders

This paper concludes that recent research on the interrelationship between gut microbiota and autism spectrum disorder (ASD) has gained significant attention. The study found that the composition of the gut microbiota in ASD patients is often markedly different from that of the general population, particularly in the species and abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, which are frequently imbalanced. The imbalance in intestinal microorganisms not only affects gut health but also disrupts the neurological functions mediated by the gut-brain axis, exacerbating the behavioral and cognitive symptoms associated with ASD. In recent years, microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), have shown some promise. The use of probiotics and prebiotics can increase the proportion of beneficial flora in the gut of patients with ASD, helping to produce anti-inflammatory short-chain fatty acids, thereby improving neurological symptoms. Additionally, FMT, which involves transplanting gut microbes from healthy individuals into ASD patients, has demonstrated significant improvements in both gut and behavioral symptoms in several studies. However, due to the high individual variability among ASD patients, a single microbial intervention is not consistently effective across all individuals. Some patients respond well to probiotics or FMT, whereas others show limited symptom improvement. This variability may be attributed to each patient's unique microbiota composition, immune status, and metabolic profile. Therefore, further research is needed to identify biomarkers that can predict the effectiveness of microbial interventions, thereby enabling more precise and individualised therapies. This review aims to provide guidance for future research and to offer a theoretical foundation and data support for exploring microbial modulation as a potential treatment for ASD.

Intestinal Microbiota and Its Influence on Human Health and Autism Spectrum Disorder (ASD)

Introduction: The intestinal microbiota plays a crucial role in human health, influencing digestion, metabolism, immune system development, and even behavior. This review aims to explore the relationship between gut microbiota and Autism Spectrum Disorder (ASD), emphasizing its potential role in the development and manifestation of ASD symptoms through immunological and metabolic pathways. Methods: Data for this review were obtained from PubMed and Science Direct, covering literature from 2011 to 2024. Inclusion criteria focused on original studies, systematic reviews, and meta-analyses discussing gut microbiota composition, dysbiosis, and its relationship with ASD. Articles were selected based on relevance, language (English or Portuguese), and the presence of empirical data. Results: The review identified 36 articles that highlight the diversity and vital functions of the gut microbiota. Dysbiosis, an imbalance in the gut microbiota, is associated with gastrointestinal issues, metabolic disorders, and neuropsychiatric conditions, including ASD. Studies indicate that children with ASD have distinct gut microbiota compositions, with reduced diversity and specific bacterial imbalances. These changes may contribute to ASD symptoms through the gut-brain axis, affecting neurotransmitter production and immune responses. Discussion: Maintaining a balanced gut microbiota is essential for overall health, and modulating the microbiota may offer therapeutic benefits for managing ASD symptoms. The changes in gut microbiota observed in individuals with ASD suggest a potential link between gut health and neuropsychiatric symptoms, highlighting the importance of dietary and probiotic interventions in maintaining gut health. Conclusion: This review underscores the potential of the gut microbiota as a therapeutic target in ASD and the importance of dietary and probiotic interventions in maintaining gut health. Further research is necessary to fully understand these interactions and develop effective microbiota-based treatments, emphasizing the need for personalized approaches in clinical applications.

Gut-brain axis: The role of gut microbiota in energy balance and body weight regulation

Obesity currently represents a major societal and health problem worldwide. Its prevalence has reached epidemic levels, and trends continue to increase; This, in turn, reflects the need for more effective preventive measures. Dietary composition is one of the main factors that modulate the structure and function of the gut microbiota. Therefore, abnormal dietary patterns or unhealthy diets can alter gut microbiota-diet interactions and alter nutrient availability and/or microbial ligands that transmit information from the gut to the brain in response to nutrient intake, thereby disrupting energy homeostasis. Accordingly, this review aims to examine how dietary composition modulates the gut microbiota and thus the potential effects of these biological products on energy homeostasis through gut-brain based mechanisms. It also assesses the knowledge gaps and advances needed to clinically implement microbiome-based strategies to improve gut-brain axis function and therefore combat obesity.

Gut Microbiota, Bacterial Translocation, and Stroke: Current Knowledge and Future Directions

Stroke is one of the most devastating pathologies in terms of mortality, cause of dementia, major adult disability, and socioeconomic burden worldwide. Despite its severity, treatment options remain limited, with no pharmacological therapies available for hemorrhagic stroke (HS) and only fibrinolytic therapy or mechanical thrombectomy for ischemic stroke (IS). In the pathophysiology of stroke, after the acute phase, many patients develop systemic immunosuppression, which, combined with neurological dysfunction and hospital management, leads to the onset of stroke-associated infections (SAIs). These infections worsen prognosis and increase mortality. Recent evidence, particularly from experimental studies, has highlighted alterations in the microbiota–gut–brain axis (MGBA) following stroke, which ultimately disrupts the gut flora and increases intestinal permeability. These changes can result in bacterial translocation (BT) from the gut to sterile organs, further contributing to the development of SAIs. Given the novelty and significance of these processes, especially the role of BT in the development of SAIs, this review summarizes the latest advances in understanding these phenomena and discusses potential therapeutic strategies to mitigate them, ultimately reducing post-stroke complications and improving treatment outcomes.

Global research trajectories in gut microbiota and functional constipation: a bibliometric and visualization study

BackgroundFunctional constipation (FC) negatively impacts quality of life and is associated with gut microbiota (GM) imbalances. Despite the growing interest in this area, a thorough analysis of research trends is missing. This study uses bibliometric methods to assess the global research on GM’s role in FC, pinpointing key topics, impactful studies, and prominent researchers to guide future research and identify gaps.MethodsIn our study, we conducted a performance analysis and science mapping using bibliometric indicators such as publication trends, author and institutional contributions, productivity, impact, keyword analysis, and collaboration networks. We employed software tools like VOSviewer, Biblioshiny, CiteSpace, and SCImago Graphica to automate the assessment of metrics including country, institutional, and journal distribution, authorship, keyword frequency, and citation patterns.ResultsFrom 2013 to 2024, annual publications on GM and FC rose from 29 to 252, with a slight decrease to 192 in 2024. Average citations per publication peaked at 11.12 in 2021, declining to 6.43 by 2024. China led in research output (37.8%), followed by the United States (14.4%) and Japan (7.5%). Bibliometric analysis identified key authors like CHEN W and ZHANG H, with 30 and 27 articles, respectively. Jiangnan University and Harvard University were top contributors, with 131 and 81 articles. Keywords analysis revealed “constipation,” “gut microbiota,” and “probiotic” as central themes, with a shift toward “gut microbiota” and “intestinal flora” in recent years. This study provides a comprehensive overview of the research landscape, highlighting leading authors, institutions, and evolving research priorities in the field.ConclusionOur review synthesizes current GM and FC research, guiding future studies. It suggests exploring GM in various GI disorders, the impact of lifestyle and drugs on GM, advanced research techniques, and probiotics/prebiotics for FC. There’s also a focus on therapies targeting GM’s effect on the gut-brain axis, paving the way for improved FC management.

Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection

Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection

Gut-Brain Axis Microbiota in Stroke Pathogenesis

Stroke is the second cause of death globally and the third cause of global disability, causing substantial health and socioeconomic problems. Clinically, Stroke is defined as brain tissue injury caused by a lack of blood supply to a particular area, resulting in permanent nerve damage or death. Stroke is also frequently associated with metabolic causes, including insulin resistance, obesity, hypertension, and type 2 diabetes mellitus (T2DM), significantly influencing the composition and abundance of the gut microbiota. Therefore, identifying potential risk factors influencing stroke prognosis and underlying pathogenic mechanisms is essential for better management and treatment of Stroke. Several studies show the existence of two-way communication between the gut and the brain through the gut microbiota. Intimate two-way interactions between the gut and the brain occur via neural (central, autonomic, and enteric nervous systems), hormonal (endocrine system), and immunological (innate and acquired immune systems) pathways, commonly referred to as the gut-microbiota axis. Brain or gut-brain axis (Gut-Brain Axis/GBA). Gut microbiota and derived metabolites play an important role in brain function by regulating GBA signaling. Recent evidence also suggests that GBA is critical in regulating immune function post-stroke. Intestinal dysbiosis provides a chronic peripheral and central inflammatory response that accelerates stroke pathology. Gut microbial dysbiosis is a significant risk factor positively correlated with poor post-stroke outcomes. This literature review summarizes the pathogenesis of ischemic Stroke, the description of the gut microbiota, and preclinical and clinical evidence indicating the pathogenic influence of gut dysbiosis in cerebral ischemic Stroke. Keywords: Stroke, Gut-brain axis, dysbiosis

Endogenous hydrogen peroxide positively regulates secretion of a gut-derived peptide in neuroendocrine potentiation of the oxidative stress response in Caenorhabditis elegans.

The gut-brain axis mediates bidirectional signaling between the intestine and the nervous system and is critical for organism-wide homeostasis. Here, we report the identification of a peptidergic endocrine circuit in which bidirectional signaling between neurons and the intestine potentiates the activation of the antioxidant response in Caenorhabditis elegans in the intestine. We identify an FMRF-amide-like peptide, FLP-2, whose release from the intestine is necessary and sufficient to activate the intestinal oxidative stress response by promoting the release of the antioxidant FLP-1 neuropeptide from neurons. FLP-2 secretion from the intestine is positively regulated by endogenous hydrogen peroxide (H2O2) produced in the mitochondrial matrix by sod-3/superoxide dismutase, and is negatively regulated by prdx-2/peroxiredoxin, which depletes H2O2 in both the mitochondria and cytosol. H2O2 promotes FLP-2 secretion through the DAG and calcium-dependent protein kinase C family member pkc-2 and by the SNAP25 family member aex-4 in the intestine. Together, our data demonstrate a role for intestinal H2O2 in promoting inter-tissue antioxidant signaling through regulated neuropeptide-like protein exocytosis in a gut-brain axis to activate the oxidative stress response.

A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging

Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer’s disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut–brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.

Neuroprotective effect of Bacillus subtilis in haloperidol induced rat model, targeting the microbiota-gut-brain axis.

Functional microbes regulate Parkinson's disease (PD), according to contemporary research. The mechanism by which probiotics (PBT) improve PD was not fully explored yet. We examined the antioxidant impact and mechanism of PBT (Bacillus subtilis) on PD using gut-brain axis regulation. To establish a model of PD, rats were given haloperidol (HAL) intraperitoneally (i.p.) in this study. The standard group received L-DOPA for 21days. After that, the motor function was assessed using different neurobehavioral tests. Further estimation comprehends the build up of alpha-synuclein, the manifestation of monoamine oxidase-B (MAO-B) activity, the deterioration of dopaminergic neurons and the induction of an oxidative stress reaction. In addition, the concentration of intestinal microbes was measured. These findings demonstrated that the administration of PBT in combination with L-dopa could alleviate motor impairments caused by HAL, the deterioration of dopaminergic neurons, and the build up of α-synuclein. Furthermore, the levels of superoxide dismutase (SOD) and dopamine were considerably raised by co-administration of L-dopa and PBT in the case of HAL-treated rats, whereas the levels of alpha-synuclein, MAO-B, and malondialdehyde (MDA) were reduced. Particularly, PBT administration reduced the gut microbial dysbiosis, which in turn raised the concentration of good bacteria i.e., Bifidobacterium and reduced the concentration of E. coli in experimental animals. These findings indicated that PBT might represent a promising candidate to inhibit the progression of Parkinson's disease by targeting the gut-brain axis.

The Gut Brain Axis, Effect of Dietary Changes and Probiotics Supplement on Depression Symptoms

The Gut Brain Axis, Effect of Dietary Changes and Probiotics Supplement on Depression Symptoms

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.

Lateral periaqueductal gray participate in the regulation of irritable bowel syndrome induced by chronic restraint stress

Irritable bowel syndrome (IBS) is a functional bowel disorder defined by recurrent abdominal pain, coupled with irregular bowel habits and alterations in the frequency as well as the consistency of stool. At present, IBS is considered as a disease of gut-brain interaction, and an increasing number of studies are focusing on the brain-gut axis. However, the brain regions associated with IBS have not been fully studied yet. In this study, we utilized the chronic restraint stress (CRS) model to evoke IBS-like symptoms in mice, which were accompanied by anxiety-like behaviors and hyperalgesia. Through cFOS staining, we observed the activation of the lateral periaqueductal gray (LPAG) in the mice after CRS. By inhibiting the activity of the LPAG through tetanus toxin or chemogenetics, we found that IBS-like symptoms could be relieved, whereas chemogenetic activation of the LPAG induced IBS-like symptoms. Finally, we utilized the classic analgesic drug sufentanil and found that it could alleviate CRS-induced IBS-like symptoms.

Novel insights into Cntnap4 in Alzheimer's disease: Intestinal flora interaction.

Alzheimer's disease (AD) is a neurodegenerative disorder with unclear etiology. This study employs single-cell RNA sequencing (scRNA-seq), high-throughput transcriptome sequencing, 16s rRNA sequencing, and animal experiments to investigate the role of the contactin-associated protein like-4 (Cntnap4) gene in AD and its interaction with intestinal flora. We found that Cntnap4 deficiency in AD mice led to increased Tau protein phosphorylation, amyloid-beta plaque accumulation, and neuronal loss. Astrocytes in Cntnap4-/- mice showed impaired amyloid-beta processing. 16 s rRNA sequencing revealed distinct intestinal flora compositions between Cntnap4-/- and control mice, indicating a potential link between gut microbiota and AD progression. Notably, GABA supplementation improved cognitive impairment, restored synaptic currents, reduced amyloid-beta plaques, and increased neuronal counts. This study highlights Cntnap4's critical role in AD and suggests gut-brain axis involvement, offering novel insights for potential therapeutic strategies.

Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats

Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.