Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related ...Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related to the occurrence of irritable bowel syndrome.This article starts with vasoactive intestinal peptide,substance P,serotonin,neuropeptide Y,corticotropin releasing factor,calcitonin gene-related peptide,cholecystokinin and other brain-gut peptides and their correlation with intestinal flora,to summarize the treatment of irritable bowel syndrome with traditional Chinese medicine in recent years.展开更多
Helicobacter pylori(H.pylori)infection is the main pathogenic factor for upper digestive tract organic diseases.In addition to direct cytotoxic and proinflammatory effects,H.pylori infection may also induce abnormalit...Helicobacter pylori(H.pylori)infection is the main pathogenic factor for upper digestive tract organic diseases.In addition to direct cytotoxic and proinflammatory effects,H.pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis,similar to other microorganisms present in the alimentary tract.The brain-gut axis integrates the central,peripheral,enteric and autonomic nervous systems,as well as the endocrine and immunological systems,with gastrointestinal functions and environmental stimuli,including gastric and intestinal microbiota.The bidirectional relationship between H.pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it,resulting in alterations in cognitive functions,food intake and appetite,immunological response,and modification of symptom sensitivity thresholds.Furthermore,disturbances in the upper and lower digestive tract permeability,motility and secretion can occur,mainly as a form of irritable bowel syndrome.Many of these abnormalities disappear following H.pylori eradication.H.pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes,or by microelement deficiency secondary to functional and morphological changes in the digestive tract.In digestive tissue,H.pylori can alter signaling in the brain-gut axis by mast cells,the main brain-gut axis effector,as H.pylori infection is associated with decreased mast cell infiltration in the digestive tract.Nevertheless,unequivocal data concerning the direct and immediate effect of H.pylori infection on the brain-gut axis are still lacking.Therefore,further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H.pylori infection pathophysiology and suggest new therapeutic approaches.展开更多
AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus...AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.展开更多
Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a...Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.展开更多
Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivit...Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission To-mography, Magnetoencephalography, and Electroen-cephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brain- imaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal dis- orders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the pheno- typic differences that determine an individual's response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual's psychological, autonomic, neuroendocrine, neurophysiological, and genetic prof ile to def ine phenotypic traits that may be at greater risk of developing sensitised states in response to gut in? am- mation or injury.展开更多
Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to t...Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.展开更多
Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional target...Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.展开更多
The recently developed magic-intensity trapping technique of neutral atoms efficiently mitigates the detrimental effect of light shifts on atomic qubits and substantially enhances the coherence time. This technique re...The recently developed magic-intensity trapping technique of neutral atoms efficiently mitigates the detrimental effect of light shifts on atomic qubits and substantially enhances the coherence time. This technique relies on applying a bias magnetic field precisely parallel to the wave vector of a circularly polarized trapping laser field. However, due to the presence of the vector light shift experienced by the trapped atoms, it is challenging to precisely define a parallel magnetic field, especially at a low bias magnetic field strength, for the magic-intensity trapping of85Rb qubits. In this work, we present a method to calibrate the angle between the bias magnetic field and the trapping laser field with the compensating magnetic fields in the other two directions orthogonal to the bias magnetic field direction. Experimentally, with a constantdepth trap and a fixed bias magnetic field, we measure the respective resonant frequencies of the atomic qubits in a linearly polarized trap and a circularly polarized one via the conventional microwave Rabi spectra with different compensating magnetic fields and obtain the corresponding total magnetic fields via the respective resonant frequencies using the Breit–Rabi formula. With known total magnetic fields, the angle is a function of the other two compensating magnetic fields.Finally, the projection value of the angle on either of the directions orthogonal to the bias magnetic field direction can be reduced to 0(4)° by applying specific compensating magnetic fields. The measurement error is mainly attributed to the fluctuation of atomic temperature. Moreover, it also demonstrates that, even for a small angle, the effect is strong enough to cause large decoherence of Rabi oscillation in a magic-intensity trap. Although the compensation method demonstrated here is explored for the magic-intensity trapping technique, it can be applied to a variety of similar precision measurements with trapped neutral atoms.展开更多
The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to fu...The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the elderly.These diseases also decrease patients’quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.展开更多
This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivot...This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.展开更多
Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the ...Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.展开更多
Insomnia,as one of the emotional diseases,has been increasing in recent years,which has a great impact on people's life and work.Therefore,researchers are eager to find a more perfect treatment.The microbiome-gut-...Insomnia,as one of the emotional diseases,has been increasing in recent years,which has a great impact on people's life and work.Therefore,researchers are eager to find a more perfect treatment.The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia.In recent years,traditional Chinese medicine(TCM)has played an increasingly important role in the treatment of insomnia,especially acupuncture and Chinese herbal medicine.It is the main method of TCM in the treatment of insomnia.This paper mainly reviews the combination degree of"microorganism-gut-brain axis"theory with TCM and acupuncture under the system of TCM.To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of"microorganismgut-brain axis"theory,in order to provide a new idea for the diagnosis and treatment of insomnia.展开更多
The gut microbiota is of growing interest to clinicians and researchers.This is because there is a growing understanding that the gut microbiota performs many different functions,including involvement in metabolic and...The gut microbiota is of growing interest to clinicians and researchers.This is because there is a growing understanding that the gut microbiota performs many different functions,including involvement in metabolic and immune processes that are systemic in nature.The liver,with its important role in detoxifying and metabolizing products from the gut,is at the forefront of interactions with the gut microbiota.Many details of these interactions are not yet known to clinicians and researchers,but there is growing evidence that normal gut microbiota function is important for liver health.At the same time,factors affecting the gut microbiota,including nutrition or medications,may also have an effect through the gut-liver axis.展开更多
In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus ...In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.展开更多
A central axis represents the core of a city’s culture,signifying its features and identity.STRETCHING from the Bell Tower and the Drum Tower in the north,to the Yongding Gate in the south,the 7.8 kilometer Beijing C...A central axis represents the core of a city’s culture,signifying its features and identity.STRETCHING from the Bell Tower and the Drum Tower in the north,to the Yongding Gate in the south,the 7.8 kilometer Beijing Central Axis has been the“cultural backbone”of the city for hundreds of years.Seen from the Drum Tower,the Central Axis is like a scroll of historical stories unfolding along its route,engendering a string of emotions in its many viewers.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially...BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.展开更多
Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and A...Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.展开更多
Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investig...Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.展开更多
基金National Training Program for Backbone Talents of Clinical Characteristic Technology Inheritance of Traditional Chinese Medicine[Chinese Medicine Renjiaofa(2019)No.36]。
文摘Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related to the occurrence of irritable bowel syndrome.This article starts with vasoactive intestinal peptide,substance P,serotonin,neuropeptide Y,corticotropin releasing factor,calcitonin gene-related peptide,cholecystokinin and other brain-gut peptides and their correlation with intestinal flora,to summarize the treatment of irritable bowel syndrome with traditional Chinese medicine in recent years.
文摘Helicobacter pylori(H.pylori)infection is the main pathogenic factor for upper digestive tract organic diseases.In addition to direct cytotoxic and proinflammatory effects,H.pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis,similar to other microorganisms present in the alimentary tract.The brain-gut axis integrates the central,peripheral,enteric and autonomic nervous systems,as well as the endocrine and immunological systems,with gastrointestinal functions and environmental stimuli,including gastric and intestinal microbiota.The bidirectional relationship between H.pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it,resulting in alterations in cognitive functions,food intake and appetite,immunological response,and modification of symptom sensitivity thresholds.Furthermore,disturbances in the upper and lower digestive tract permeability,motility and secretion can occur,mainly as a form of irritable bowel syndrome.Many of these abnormalities disappear following H.pylori eradication.H.pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes,or by microelement deficiency secondary to functional and morphological changes in the digestive tract.In digestive tissue,H.pylori can alter signaling in the brain-gut axis by mast cells,the main brain-gut axis effector,as H.pylori infection is associated with decreased mast cell infiltration in the digestive tract.Nevertheless,unequivocal data concerning the direct and immediate effect of H.pylori infection on the brain-gut axis are still lacking.Therefore,further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H.pylori infection pathophysiology and suggest new therapeutic approaches.
基金Supported by Division of Intramural ResearchNational Institute of Nursing Research to W.A.H.No.1ZIANR000018-01-05
文摘AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.
文摘Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.
基金Supported by A Medical Research Council Career Establi-shment Award and the Rosetrees Trust
文摘Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission To-mography, Magnetoencephalography, and Electroen-cephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brain- imaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal dis- orders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the pheno- typic differences that determine an individual's response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual's psychological, autonomic, neuroendocrine, neurophysiological, and genetic prof ile to def ine phenotypic traits that may be at greater risk of developing sensitised states in response to gut in? am- mation or injury.
基金This paper was supported by the National Natural Science Foundation of China(.81473597 and 81630104)the China National Funds for Distinguished Young Scientists(30825046)the Beijing Municipal Natural Science Foundation(7152093).
文摘Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.
基金supported by the National Natural Science Foundation of China,No.82204663the Natural Science Foundation of Shandong Province,No.ZR2022QH058(both to TZ).
文摘Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12104414,12122412,12104464,and 12104413)the China Postdoctoral Science Foundation(Grant No.2021M702955).
文摘The recently developed magic-intensity trapping technique of neutral atoms efficiently mitigates the detrimental effect of light shifts on atomic qubits and substantially enhances the coherence time. This technique relies on applying a bias magnetic field precisely parallel to the wave vector of a circularly polarized trapping laser field. However, due to the presence of the vector light shift experienced by the trapped atoms, it is challenging to precisely define a parallel magnetic field, especially at a low bias magnetic field strength, for the magic-intensity trapping of85Rb qubits. In this work, we present a method to calibrate the angle between the bias magnetic field and the trapping laser field with the compensating magnetic fields in the other two directions orthogonal to the bias magnetic field direction. Experimentally, with a constantdepth trap and a fixed bias magnetic field, we measure the respective resonant frequencies of the atomic qubits in a linearly polarized trap and a circularly polarized one via the conventional microwave Rabi spectra with different compensating magnetic fields and obtain the corresponding total magnetic fields via the respective resonant frequencies using the Breit–Rabi formula. With known total magnetic fields, the angle is a function of the other two compensating magnetic fields.Finally, the projection value of the angle on either of the directions orthogonal to the bias magnetic field direction can be reduced to 0(4)° by applying specific compensating magnetic fields. The measurement error is mainly attributed to the fluctuation of atomic temperature. Moreover, it also demonstrates that, even for a small angle, the effect is strong enough to cause large decoherence of Rabi oscillation in a magic-intensity trap. Although the compensation method demonstrated here is explored for the magic-intensity trapping technique, it can be applied to a variety of similar precision measurements with trapped neutral atoms.
文摘The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the elderly.These diseases also decrease patients’quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.
文摘This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.
基金This work was financially supported by the Second Batch of Medical and Health Science and Technology Plan(self-financing)Projects in Shantou in 2020,Shantou Science and Technology Bureau Document Shantou([2020]No.58).
文摘Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.
文摘Insomnia,as one of the emotional diseases,has been increasing in recent years,which has a great impact on people's life and work.Therefore,researchers are eager to find a more perfect treatment.The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia.In recent years,traditional Chinese medicine(TCM)has played an increasingly important role in the treatment of insomnia,especially acupuncture and Chinese herbal medicine.It is the main method of TCM in the treatment of insomnia.This paper mainly reviews the combination degree of"microorganism-gut-brain axis"theory with TCM and acupuncture under the system of TCM.To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of"microorganismgut-brain axis"theory,in order to provide a new idea for the diagnosis and treatment of insomnia.
文摘The gut microbiota is of growing interest to clinicians and researchers.This is because there is a growing understanding that the gut microbiota performs many different functions,including involvement in metabolic and immune processes that are systemic in nature.The liver,with its important role in detoxifying and metabolizing products from the gut,is at the forefront of interactions with the gut microbiota.Many details of these interactions are not yet known to clinicians and researchers,but there is growing evidence that normal gut microbiota function is important for liver health.At the same time,factors affecting the gut microbiota,including nutrition or medications,may also have an effect through the gut-liver axis.
基金supported by the Russian Science Foundation(Grant No.23-25-00152).
文摘In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.
文摘A central axis represents the core of a city’s culture,signifying its features and identity.STRETCHING from the Bell Tower and the Drum Tower in the north,to the Yongding Gate in the south,the 7.8 kilometer Beijing Central Axis has been the“cultural backbone”of the city for hundreds of years.Seen from the Drum Tower,the Central Axis is like a scroll of historical stories unfolding along its route,engendering a string of emotions in its many viewers.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金Supported by the National Key Research and Development Project of China,No.2019YFC1711605National Natural Science Foundation of China,No.81904257Medical Innovation Research Project of Science and Technology Commission of Shanghai Municipality,No.21Y11923100.
文摘BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.
基金supported by the National Natural Science Foundation of China,Nos.82101271 (to WL),82171178 (to JL)Basic and Applied Basic Research Foundation of Guangdong Province,Nos.2020A1515110317 (to WL),2021A1515010705 (to WL)+1 种基金Young Talent Support Project of Guangzhou Association for Science and Technology (to WL)Technology Key Project of Shenzhen,No.JCYJ202001091 14612308 (to ZS)。
文摘Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.
基金supported by fund from the National Natural Science Foundation of China (32172322)Shandong Provincial Natural Science Foundation (ZR2023QC291)Shandong Traditional Chinese Medicine Technology Project (Q-2023130)。
文摘Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.