Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanis...Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.展开更多
The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enh...The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.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
In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following tran...In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believe...Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.展开更多
In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).C...In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.展开更多
This editorial,inspired by a recent study published in the World Journal of Gastrointestinal Oncology,covers the research findings on microbiota changes in various diseases.In recurrent colorectal polyps,the abundance...This editorial,inspired by a recent study published in the World Journal of Gastrointestinal Oncology,covers the research findings on microbiota changes in various diseases.In recurrent colorectal polyps,the abundances of Klebsiella,Parvimonas,and Clostridium increase,while those of Bifidobacterium and Lactoba-cillus decrease.This dysbiosis may promote the formation and recurrence of polyps.Similar microbial changes have also been observed in colorectal cancer,inflammatory bowel disease,autism spectrum disorder,and metabolic syndrome,indicating the role of increased pathogens and decreased probiotics in these conditions.Regulating the gut microbiota,particularly by increasing probiotic levels,may help prevent polyp recurrence and promote gut health.This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.展开更多
BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted ...BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.展开更多
BACKGROUND Recent research indicates that the intestinal microbial community,known as the gut microbiota,may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).To understand this relati...BACKGROUND Recent research indicates that the intestinal microbial community,known as the gut microbiota,may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).To understand this relationship,this study used a compre-hensive bibliometric analysis to explore and analyze the currently little-known connection between gut microbiota and NAFLD,as well as new findings and possible future pathways in this field.AIM To provide an in-depth analysis of the current focus issues and research deve-lopments on the interaction between gut microbiota and NAFLD.METHODS In this study,all data were collected from the Web of Science Core Collection,and the related searches were completed on one day(February 21,2024).The data were stored in plain text format to facilitate subsequent analysis.VOSviewer 1.6.20 and CiteSpace 6.1R6 Basic were used for knowledge graph construction and bibliometric analysis.RESULTS The study included a total of 1256 articles published from 2013 to 2023,and the number of published papers demonstrated an upward trend,reaching a peak in the last two years.The University of California,San Diego held the highest citation count,while Shanghai University of Traditional Chinese Medicine in China led in the number of published works.The journal"Nutrients"had the highest publication count,while"Hepatology"was the most frequently cited.South Korean author Suk Ki Tae was the most prolific researcher.The co-cited keyword cluster labels revealed ten major clusters,namely cortisol,endothelial dysfunction,carbohydrate metabolism,myocardial infarction,non-alcoholic steatohepatitis,lipotoxicity,glucagon-like peptide-1,non-islet dependent,ethnicity,and microRNA.Keyword outbreak analysis highlighted metabolic syndrome,hepatic steatosis,insulin resistance,hepatocellular carcinoma,cardiovascular disease,intestinal permeability,and intestinal bacterial overgrowth as prominent areas of intense research.CONCLUSION Through the quantitative analysis of relevant literature,the current research focus and direction of gut microbiota and NAFLD can be more clearly understood,which helps us better understand the pathogenesis of NAFLD,and also opens up innovative solutions and strategies for the treatment of NAFLD.展开更多
Pampus argenteus is a commercially valuable species in many countries.Its artificial cultivation has been impacted by intestinal flatulence,leading to increased mortality.However,the role of gut microbiota in this pro...Pampus argenteus is a commercially valuable species in many countries.Its artificial cultivation has been impacted by intestinal flatulence,leading to increased mortality.However,the role of gut microbiota in this process remains unclear.Therefore,this study utilized high-throughput sequencing of 16S rRNA genes to investigate the gut microbiota in both flatulent and healthy P.argenteus.A total of 227571 high-quality and classifiable reads,representing 312 Amplicon Sequence Variants(ASVs),were obtained.Proteobacteria emerged as the predominant phylum in all samples,with the flatulent group displaying the highest relative abundance(85.3%).Microbial diversity was significantly greater in samples from water than those from tissues.Composition analysis using Bray-Curtis distance via CPCoA revealed distinct gut microbiota compositions between the samples with flatulence and the healthy samples.Co-occurrence network analysis demonstrated that the bacterial community in the flatulent group exhibited disorder due to the high abundance of Vibrio.Functional predictive analysis(PICRUSt2)indicated that flatulence in P.argenteus was associated with impaired methane and lipid metabolism,potentially resulting in excessive methane synthesis utilizing hydrogen and acetic acid as substrates produced by Clostridium sensu stricto 1,Cetobacterium,and Peptoclostridium.This study holds significant implications for early diagnosis and prevention of intestinal flatulence through the regulation of gut microbiota.展开更多
The role of the gut microbiota in the pathogenesis and treatment of hepatic encephalopathy (HE) has garnered increasing attention due to significant advancements in understanding the gut microbiota over recent years. ...The role of the gut microbiota in the pathogenesis and treatment of hepatic encephalopathy (HE) has garnered increasing attention due to significant advancements in understanding the gut microbiota over recent years. A growing body of evidence from laboratory and clinical studies highlights a substantial relationship between gut microbiota and HE. Identifying the role of gut microbiota in maintaining normal cognitive function, including its influence on the gut barrier and immune cells, is essential to elucidate the mechanisms underlying the development of HE. This understanding offers novel perspectives for its prevention and treatment. This paper provides a comprehensive review of the research progress concerning the gut microbiota, HE, and their interrelationship, along with current treatment methods for HE. Furthermore, it outlines the limitations and challenges associated with microbiota-based therapeutic research.展开更多
BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopath...Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.展开更多
There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous sys...There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.展开更多
The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefo...The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.展开更多
BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabol...BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.展开更多
In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer...In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.展开更多
AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples...AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.展开更多
D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the imp...D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.展开更多
基金supported by Fundamental Research Funds for the Central Universities(2022-ZXFZJJ-028).
文摘Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.
基金supported by the National Natural Science Foundation of China,No.82003965the Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2024MS167(to LH)+2 种基金the Xinglin Scholar Program of Chengdu University of Traditional Chinese Medicine,No.QJRC2022033(to LH)the Improvement Plan for the'Xinglin Scholar'Scientific Research Talent Program at Chengdu University of Traditional Chinese Medicine,No.XKTD2023002(to LH)the 2023 National Project of the College Students'Innovation and Entrepreneurship Training Program at Chengdu University of Traditional Chinese Medicine,No.202310633028(to FD)。
文摘The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
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 Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province,No.2023GBYJ-YL-1.
文摘In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
文摘Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.
基金Supported by the Postdoctoral Scholarship Grant,No.5552/2024 PROPG/PROPE N°06/2024.
文摘In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.
文摘This editorial,inspired by a recent study published in the World Journal of Gastrointestinal Oncology,covers the research findings on microbiota changes in various diseases.In recurrent colorectal polyps,the abundances of Klebsiella,Parvimonas,and Clostridium increase,while those of Bifidobacterium and Lactoba-cillus decrease.This dysbiosis may promote the formation and recurrence of polyps.Similar microbial changes have also been observed in colorectal cancer,inflammatory bowel disease,autism spectrum disorder,and metabolic syndrome,indicating the role of increased pathogens and decreased probiotics in these conditions.Regulating the gut microbiota,particularly by increasing probiotic levels,may help prevent polyp recurrence and promote gut health.This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.
基金Supported by the Shanghai Science and Technology Commission Project,No.21010504300Shanghai Jiading District Traditional Chinese Medicine Key Specialty Construction Project,No.2020-JDZYYZDZK-01.
文摘BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.
文摘BACKGROUND Recent research indicates that the intestinal microbial community,known as the gut microbiota,may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).To understand this relationship,this study used a compre-hensive bibliometric analysis to explore and analyze the currently little-known connection between gut microbiota and NAFLD,as well as new findings and possible future pathways in this field.AIM To provide an in-depth analysis of the current focus issues and research deve-lopments on the interaction between gut microbiota and NAFLD.METHODS In this study,all data were collected from the Web of Science Core Collection,and the related searches were completed on one day(February 21,2024).The data were stored in plain text format to facilitate subsequent analysis.VOSviewer 1.6.20 and CiteSpace 6.1R6 Basic were used for knowledge graph construction and bibliometric analysis.RESULTS The study included a total of 1256 articles published from 2013 to 2023,and the number of published papers demonstrated an upward trend,reaching a peak in the last two years.The University of California,San Diego held the highest citation count,while Shanghai University of Traditional Chinese Medicine in China led in the number of published works.The journal"Nutrients"had the highest publication count,while"Hepatology"was the most frequently cited.South Korean author Suk Ki Tae was the most prolific researcher.The co-cited keyword cluster labels revealed ten major clusters,namely cortisol,endothelial dysfunction,carbohydrate metabolism,myocardial infarction,non-alcoholic steatohepatitis,lipotoxicity,glucagon-like peptide-1,non-islet dependent,ethnicity,and microRNA.Keyword outbreak analysis highlighted metabolic syndrome,hepatic steatosis,insulin resistance,hepatocellular carcinoma,cardiovascular disease,intestinal permeability,and intestinal bacterial overgrowth as prominent areas of intense research.CONCLUSION Through the quantitative analysis of relevant literature,the current research focus and direction of gut microbiota and NAFLD can be more clearly understood,which helps us better understand the pathogenesis of NAFLD,and also opens up innovative solutions and strategies for the treatment of NAFLD.
基金funded by the National Key R&D Program of China(No.2022YFD2400100)the Ningbo 2025 Major Project of Science Technology and Innovation(No.2021Z003)+5 种基金the Public Welfare Program of Ningbo City(Science and Technology Special Commissioner Project)(No.2022S204)the National Natural Science Foundation of China(Nos.31872195,42076118 and 42306114)the China Postdoctoral Science Foundation(No.2022M721729)the General Scientific Research Projects of Zhejiang Provincial Department of Education(No.Y202249062)the Ningbo Public Welfare Science and Technology Project(No.2021S061)the Ningbo Yongjiang Talent Introduction Programme(No.2021B-029-C)。
文摘Pampus argenteus is a commercially valuable species in many countries.Its artificial cultivation has been impacted by intestinal flatulence,leading to increased mortality.However,the role of gut microbiota in this process remains unclear.Therefore,this study utilized high-throughput sequencing of 16S rRNA genes to investigate the gut microbiota in both flatulent and healthy P.argenteus.A total of 227571 high-quality and classifiable reads,representing 312 Amplicon Sequence Variants(ASVs),were obtained.Proteobacteria emerged as the predominant phylum in all samples,with the flatulent group displaying the highest relative abundance(85.3%).Microbial diversity was significantly greater in samples from water than those from tissues.Composition analysis using Bray-Curtis distance via CPCoA revealed distinct gut microbiota compositions between the samples with flatulence and the healthy samples.Co-occurrence network analysis demonstrated that the bacterial community in the flatulent group exhibited disorder due to the high abundance of Vibrio.Functional predictive analysis(PICRUSt2)indicated that flatulence in P.argenteus was associated with impaired methane and lipid metabolism,potentially resulting in excessive methane synthesis utilizing hydrogen and acetic acid as substrates produced by Clostridium sensu stricto 1,Cetobacterium,and Peptoclostridium.This study holds significant implications for early diagnosis and prevention of intestinal flatulence through the regulation of gut microbiota.
基金supported by the Health Commission of Sichuan Province(Popularization of Application Project,Grant No.21PJ182).
文摘The role of the gut microbiota in the pathogenesis and treatment of hepatic encephalopathy (HE) has garnered increasing attention due to significant advancements in understanding the gut microbiota over recent years. A growing body of evidence from laboratory and clinical studies highlights a substantial relationship between gut microbiota and HE. Identifying the role of gut microbiota in maintaining normal cognitive function, including its influence on the gut barrier and immune cells, is essential to elucidate the mechanisms underlying the development of HE. This understanding offers novel perspectives for its prevention and treatment. This paper provides a comprehensive review of the research progress concerning the gut microbiota, HE, and their interrelationship, along with current treatment methods for HE. Furthermore, it outlines the limitations and challenges associated with microbiota-based therapeutic research.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
基金The current project is funded by Shandong Provincial Natural Science Foundation,China(ZR2020MH370)Major Science and Technology Innovation in Shandong Province(2017CXGC1307)Ji’nan Science and Technology Project(201303055)。
文摘Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.
基金supported by the National Natural Science Foundation of China,Nos.82105019(to YC),82271218(to CZ)Natural Science Foundation of Tianjin Municipality Foundation,No.20JCZDJC00540(to CZ).
文摘There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.
基金supported by the National Key Research and Development Program,China(Grant Nos.:2021YFC2101500 and 2021YFC2103900)the National Natural Science Foundation of China(Grant Nos.:22278335 and 21978236)the Natural Science Basic Research Program of Shaanxi,China(Grant No.:2023-JC-JQ-17).
文摘The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.
基金Supported by National Natural Science Foundation of China,No.82160843.
文摘BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.
基金financially supported by the National Natural Science Foundation of China(U2004104)the Natural Science Foundation of Henan Province(202300410080)+2 种基金the Key Project of Henan Education Committee(21A310005)the Internal Fund of Hebei University of Economics and Business(2020ZD10)the Postgraduate“Talent Program”of Henan University(SYL20060187 and SYL20060189)。
文摘In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.
文摘AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.
基金funded by the National Natural Science Foundation of China(No.32030083)。
文摘D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.
