The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune respon...The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora(dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens(molecular mimicry). Activated gutderived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.展开更多
Objective:To determine the mechanism whereby rhubarb(Rheum tanguticum MAXIM.Ex BALF.)may ameliorate cognitive dysfunction through regulation of the intestinal microbiome.Methods:We used a rat model of human microbiome...Objective:To determine the mechanism whereby rhubarb(Rheum tanguticum MAXIM.Ex BALF.)may ameliorate cognitive dysfunction through regulation of the intestinal microbiome.Methods:We used a rat model of human microbiome-associated(HMA)-AD to characterize the therapeutic effect of rhubarb on cognitive dysfunction by assessing learning and spatial memory,tissue pathology,and neurotransmitter expression in brain tissue.Then,16S rRNA gene sequencing was used to analyze the intestinal microbial composition of the rats before and after rhubarb intervention,to determine whether changes in the intestinal microbiome might underpin the beneficial effect of rhubarb on cognitive dysfunction.Results:Morris water maze experiments showed that the learning and spatial memory of HMAAD rats were improved after rhubarb administration.Examination of brain sections showed that rhubarb had a protective effect on neurons in the brain tissue of HMA-AD rats.Brain tissue neurotransmitter analysis showed that rhubarb significantly reduces the 5-hydorxytryptamine concentration in the hippocampus of HMA-AD rats(P Z.0013).Furthermore,rhubarb affected the abundance of the Lachnospiraceae_NK4A136_group and Lactobacillus in the large intestine.Conclusion:This study suggests that rhubarb ameliorates cognitive dysfunction in rats with HMA-AD by regulating the abundance of beneficial bacteria,which likely affects the concentration of 5-hydorxytryptamine in the hippocampus.展开更多
BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activit...BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.展开更多
Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chines...Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.展开更多
BACKGROUND Necrotizing enterocolitis(NEC)is a multifactorial disease that predominantly affects premature neonates.Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates.The main risk fac...BACKGROUND Necrotizing enterocolitis(NEC)is a multifactorial disease that predominantly affects premature neonates.Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates.The main risk factor for NEC in term infants is mesenteric hypoperfusion associated with ductaldependent congenital heart disease(CHD)that eventually leads to intestinal ischemia.The incidence of NEC in neonates with critical CHD is 6.8%-13%.However,the role of the intestinal microbiome in NEC pathogenesis in infants with ductal-dependent CHD remains unclear.CASE SUMMARY A male term neonate with right atrial isomerism underwent modified Blalock-Taussig shunt placement on the 14^(th)day of life and had persistent mesenteric hypoperfusion after surgery.The patient had episodes of NEC stageⅡA on the 1^(st)and 28^(th)days after cardiac surgery.Fecal microbial composition was analyzed before and after cardiac surgery by sequencing region V4 of the 16S rRNA gene.Before surgery,species belonging to genera Veillonella and Clostridia and class Gammaproteobacteria were detected,Bifidobacteriaceae showed a low abundance.The first NEC episode was associated with postoperative hemodynamic instability,intestinal ischemiareperfusion injury during cardiopulmonary bypass,and a high abundance of Clostridium paraputrificum(Clostridium sensu stricto I)(56.1%).Antibacterial therapy after the first NEC episode resulted in increased abundance of Gammaproteobacteria,decreased abundance of Firmicutes,and low alpha diversity.These changes in the microbial composition promoted the growth of Clostridium sensu strictoⅠ(72.0%)before the second NEC episode.CONCLUSION A high abundance of Clostridium sensu strictoⅠand mesenteric hypoperfusion may have contributed to NEC in the present case.展开更多
Polystyrene nanoplastics(PS-NPs)and 3,3′,4,4′-tetrachlorobiphenyl(PCB77)are common pollutants in freshwater aquatic environments.To investigate the separate and combined toxicity of these two pollutants on the fresh...Polystyrene nanoplastics(PS-NPs)and 3,3′,4,4′-tetrachlorobiphenyl(PCB77)are common pollutants in freshwater aquatic environments.To investigate the separate and combined toxicity of these two pollutants on the freshwater blunt snout bream(Megalobrama amblycephala),270 juveniles were randomly assigned to six exposure treatments:the control group,CT(free of PS-NPs and PCB77),three single exposure groups,PS-L(0.2 mg/L PS-NPs),PS-H(2 mg/L PS-NPs),PCB(0.01 mg/L PCB77),and two combined exposure groups,PP-L(0.2 mg/L PS-NPs+0.01 mg/L PCB77)and PP-H(2 mg/L PS-NPs+0.01 mg/L PCB77).After a seven-day exposure,the tissue histopathology,antioxidant capacity,inflammatory response,and gut microbiome composition of fish were analyzed.The results showed that tissue fluorescence intensity of PS-NPs increases as the exposure levels of PS-NPs increase,and the combined exposure groups exhibited higher fluorescence intensity compared to their single PS-NPs exposure groups.Histopathological analysis showed that the exposure groups exhibited varying degrees of damage to the intestinal tissue compared to the control group,with more severe damage observed in the combined exposure groups.Additionally,liver damage was evident in the PS-H,PP-L and PP-H groups.Furthermore,the highest catalase(CAT)activities and malondialdehyde(MDA)contents were found in the intestine and liver of fish in the PP-L and PP-H groups.The mRNA levels of inflammatory factors(il,il-1β,il-8,il-6,il-10,and tnf-α)were up-regulated in the PS-H,PP-L and PP-H groups compared to those of the CT group.In addition,remarkable alternations in the intestinal microbiome compositions were observed among the groups:the abundance of Verrucomicrobiome and Planctomycetota increased in all exposed groups compared to that of the control group,while the abundance of Actinobacteriota was significantly reduced in the exposure groups.Functional prediction of microbiota indicated that the amino acid and carbohydrate metabolism,as well as intestinal structure,were impaired in the PS-NPs and PCB77 exposure groups.The results suggested that the toxicity of PS-NPs on M.amblycephala including tissue injury,oxidative stress,and disturbance of intestinal microbiota,depends not only on concentration but also increases when co-exposed to PCB77.This finding raises concerns about the ecological safety in freshwater aquatic environments.展开更多
The onset and progression of type 2 diabetes mellitus(T2DM)are strongly associated with imbalances in gut bacteria,making the gut microbiome a new potential therapeutic focus.This commentary examines the recent public...The onset and progression of type 2 diabetes mellitus(T2DM)are strongly associated with imbalances in gut bacteria,making the gut microbiome a new potential therapeutic focus.This commentary examines the recent publication in World Journal of Diabetes.The article explores the association between T2DM and gut microbiota,with a focus on the pathophysiological changes related to dysbiosis.It proposes innovative microbiome-targeted therapeutic strategies and evaluates the challenges and future directions of such approaches.This editorial summarizes the key points of their discussion of the role of the gut microbiome in T2DM and elaborates on the influence of specific gut microbial species on the disease through the host–microbiota metabolic axis.It provides new insights for future research on gut-microbiota-based interventions for T2DM.展开更多
Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in dis...Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.展开更多
Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic r...Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic reactions in the body.Evidence suggests that intestinal stem cells(ISCs),which are phenotypic precursors of various intestinal epithelial cells,play a significant role in the regulation of intestinal barrier function and homeostasis.The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs.As a result,the effects exerted by dietary factors,intestinal microbiomes,and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed.This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota,related metabolites,and ISCs,with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body.Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.展开更多
The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a...The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.展开更多
Although intestinal fungi play important roles in host health and disease,the composition and diversity of fungal communities remain poorly reported in fish.In this study,fungi in the fore-,mid-,and hindintestine of t...Although intestinal fungi play important roles in host health and disease,the composition and diversity of fungal communities remain poorly reported in fish.In this study,fungi in the fore-,mid-,and hindintestine of tilapia(Oreochromis mossambicus)and bighead carp(Aristichthys nobilis)from Hongchaojiang Reservoir in Guangxi,China were investigated by ITS sequencing.Based on this,we obtained 1763478 high-quality tags,which clustered into 1089 operational taxonomic units(OTUs).In total,404 OTUs were annotated,of which 310,68,and 26 belonged to Ascomycota,Basidiomycota,and other,respectively.Results show significant differences in the community composition of intestinal fungi between tilapia and bighead carp but not within their different intestinal segments.Furthermore,154 of the 404 annotated OTUs were considered reliable and were classified into three trophic modes and nine guilds.The three trophic modes consisted of 108 OTUs of saprotrophic fungi,41 OTUs of pathotrophic fungi,and five OTUs of symbiotrophic fungi.The top three most abundant OTUs overall(i.e.,Otu000002,Scopulariopsis acremonium;Otu000018,Alternaria palandui;Otu000034,Aureobasidium pullulans)showed lower abundance in the hind-intestinal segments of bighead carp,suggesting uneven distribution of these fungi in this species.In addition,saprotrophic and pathotrophic fungi were markedly decreased in the hindintestine.It is indicated that the fungal community was not only related to host species specificity but also to the respective physiological functions of different intestinal segments.These findings provide valuable information on the composition,structure,and potential function of the intestinal fungi community associated with different intestinal segments in tilapia and bighead carp under natural conditions,thus highlighting the importance of fungi as an integral part of the inte stinal microbiota in maintaining host health.展开更多
Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbi...Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbiome and short-chain fatty acids(SCFAs)following alcohol intoxication and burn injury and to determine whether these changes are associated with intestinal inflammation.Methods 10–12-week-old C57BL/6 male and female mice were subjected to ethanol intoxication and a 12.5%total body surface area scald burn injury.The following day,mice were euthanised and faecal contents from the caecum and small intestine(SI)were harvested for 16S sequencing for microbial analysis and caecum contents underwent high-performance liquid chromatography mass spectroscopy to assess SCFAs.Results The intestinal microbiome of ethanol burn(EB)mice exhibited decreased alpha diversity and distinct beta diversity compared with sham vehicle(SV).EB faeces were marked by increased Proteobacteria and many pathobionts.EB caecum faeces exhibited a significant decrease in butyrate and a downward trend in acetate and total SCFAs.SCFA changes correlated with microbial changes particularly in the SI.Treatment of murine duodenal cell clone-K(MODE-K)cells with faecal slurries led to upregulation of interleukin-6(IL-6)from EB faeces compared with SV faeces which correlated with levels of Enterobacteriaceae.However,supplementation of butyrate reduced faecal slurry-induced MODE-K cells IL-6 release.Conclusion Together,these findings suggest that alcohol and burn injury induce bacterial dysbiosis and a decrease in SCFAs,which together can promote intestinal inflammation and barrier disruption,predisposing to postinjury pathology.展开更多
Monascus-fermented red mold rice(RMR)has excellent physiological efficacy on lipid metabolism and liver function.This study investigated the ameliorative effects of monascin(MS)from RMR on alcoholic liver injury(ALI)i...Monascus-fermented red mold rice(RMR)has excellent physiological efficacy on lipid metabolism and liver function.This study investigated the ameliorative effects of monascin(MS)from RMR on alcoholic liver injury(ALI)in mice,and further illustrated its mechanism of action.Results indicated that dietary MS intervention obviously ameliorated lipid metabolism and liver function in mice with over-drinking.In addition,MS intervention alleviated alcohol-induced oxidative stress in the liver by reducing the hepatic activities of lactate dehydrogenase(LDH)and hepatic levels of malondialdehyde(MDA),increasing the hepatic activities of catalase(CAT),superoxide dismutase(SOD),alcohol dehydrogenase(ADH)and hepatic levels of glutathione(GSH).16S rRNA amplicon sequencing showed that excessive drinking had a significant effect on the composition of the gut microbiota in mice.MS intervention was beneficial to ameliorate intestinal microbiota dysbiosis by elevating the proportion of Lactobacillus,Lachnospiraceae_UCG-006,Coriobacteriales,etc.,but decreasing the proportion of Staphylococcus,Muribaculaceae,Desulfovibrionaceae,etc.Additionally,correlation analysis indicated that the key intestinal bacterial taxa intervened by MS were closely related to some biochemical indicators of lipid metabolism,liver function and oxidative stress.Moreover,liver metabolomics analysis revealed that dietary MS supplementation significantly regulated the levels of liver metabolites involved in taurine and hypotaurine metabolism,riboflavin metabolism,and purine metabolism,etc.Furthermore,MS intervention regulated gene transcription and protein expression associated with lipid metabolism and oxidative stress in the liver.In short,these findings suggest that MS mitigates alcohol-induced hepatic oxidative damage through modulating the intestinal microbiome and liver metabolic pathway,and thus can be served as a functional component to prevent alcoholic liver disease.展开更多
The incidence and prevalence of asthma have increased remarkably in recent years.There are lots of factors contributing to the occurrence and development of asthma.With the improvement of sequencing technology,it has ...The incidence and prevalence of asthma have increased remarkably in recent years.There are lots of factors contributing to the occurrence and development of asthma.With the improvement of sequencing technology,it has been found that the microbiome plays an important role in the formation of asthma in early life.The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention.The environmental microbiome influences the occurrence of asthma by shaping the human microbiome.The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells(special Tregs).Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life,which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis.It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma.This review aims to summarize the recent advances in the research of microbiome,its relationship with asthma,and the possible mechanism of the microbiome in the occurrence and development of asthma.The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy.However,further study of"when and how"to regulate microbiome is still needed.展开更多
Intestinal bacteria contribute to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Recently developed microbial profiling techniques are beginning to shed light on the nature of the changes in the gut micr...Intestinal bacteria contribute to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Recently developed microbial profiling techniques are beginning to shed light on the nature of the changes in the gut microbiota that accompany NAFLD and non-alcoholic steatohepatitis(NASH).In this review,we summarize the role of gut microbiota in the development of NAFLD,NASH,and hepatocellular carcinoma(HCC).We highlight the mechanisms by which gut microbiota contribute to NAFLD/NASH,including through alterations in gut epithelial permeability,choline metabolism,endogenous alcohol production,release of inflammatory cytokines,regulation of hepatic Toll-like receptor(TLR),and bile acid metabolism.In addition,we analyze possible mechanisms for enhanced hepatic carcinogenesis,including alterations in bile acid metabolism,release of inflammatory cytokines,and expression of TLR-4.Finally,we describe therapeutic approaches for NAFLD/NASH and preventive strategies for HCC involving modulation of the intestinal microbiota or affected host pathways.Although recent studies have provided useful information,large-scale prospective studies are required to better characterize the intestinal microbiota and metabolome,in order to demonstrate a causative role for changes in the gut microbiota in the etiology of NAFLD/NASH,to identify new therapeutic strategies for NAFLD/NASH,and to develop more effective methods of preventing HCC.展开更多
Systemic autoimmune diseases are a genetic and environmental factors. Although group of heterogeneous disorders caused by both numerous causal genes have been identified by genome-wide association studies （GWAS）, th...Systemic autoimmune diseases are a genetic and environmental factors. Although group of heterogeneous disorders caused by both numerous causal genes have been identified by genome-wide association studies （GWAS）, these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogen- esis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body＇s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing （NGS） technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.展开更多
文摘The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora(dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens(molecular mimicry). Activated gutderived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.
基金the National Natural Science Foundation of China(81673562).
文摘Objective:To determine the mechanism whereby rhubarb(Rheum tanguticum MAXIM.Ex BALF.)may ameliorate cognitive dysfunction through regulation of the intestinal microbiome.Methods:We used a rat model of human microbiome-associated(HMA)-AD to characterize the therapeutic effect of rhubarb on cognitive dysfunction by assessing learning and spatial memory,tissue pathology,and neurotransmitter expression in brain tissue.Then,16S rRNA gene sequencing was used to analyze the intestinal microbial composition of the rats before and after rhubarb intervention,to determine whether changes in the intestinal microbiome might underpin the beneficial effect of rhubarb on cognitive dysfunction.Results:Morris water maze experiments showed that the learning and spatial memory of HMAAD rats were improved after rhubarb administration.Examination of brain sections showed that rhubarb had a protective effect on neurons in the brain tissue of HMA-AD rats.Brain tissue neurotransmitter analysis showed that rhubarb significantly reduces the 5-hydorxytryptamine concentration in the hippocampus of HMA-AD rats(P Z.0013).Furthermore,rhubarb affected the abundance of the Lachnospiraceae_NK4A136_group and Lactobacillus in the large intestine.Conclusion:This study suggests that rhubarb ameliorates cognitive dysfunction in rats with HMA-AD by regulating the abundance of beneficial bacteria,which likely affects the concentration of 5-hydorxytryptamine in the hippocampus.
基金Supported by the "333 Scientific Project" of Jiangsu Province in 2020, No. BRA2020237the Science and Technology Project of Suqian, Jiangsu Province in 2020, No. Z2020057
文摘BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.
文摘Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.
基金Supported by the Russian Science Foundation,No.22-25-00484。
文摘BACKGROUND Necrotizing enterocolitis(NEC)is a multifactorial disease that predominantly affects premature neonates.Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates.The main risk factor for NEC in term infants is mesenteric hypoperfusion associated with ductaldependent congenital heart disease(CHD)that eventually leads to intestinal ischemia.The incidence of NEC in neonates with critical CHD is 6.8%-13%.However,the role of the intestinal microbiome in NEC pathogenesis in infants with ductal-dependent CHD remains unclear.CASE SUMMARY A male term neonate with right atrial isomerism underwent modified Blalock-Taussig shunt placement on the 14^(th)day of life and had persistent mesenteric hypoperfusion after surgery.The patient had episodes of NEC stageⅡA on the 1^(st)and 28^(th)days after cardiac surgery.Fecal microbial composition was analyzed before and after cardiac surgery by sequencing region V4 of the 16S rRNA gene.Before surgery,species belonging to genera Veillonella and Clostridia and class Gammaproteobacteria were detected,Bifidobacteriaceae showed a low abundance.The first NEC episode was associated with postoperative hemodynamic instability,intestinal ischemiareperfusion injury during cardiopulmonary bypass,and a high abundance of Clostridium paraputrificum(Clostridium sensu stricto I)(56.1%).Antibacterial therapy after the first NEC episode resulted in increased abundance of Gammaproteobacteria,decreased abundance of Firmicutes,and low alpha diversity.These changes in the microbial composition promoted the growth of Clostridium sensu strictoⅠ(72.0%)before the second NEC episode.CONCLUSION A high abundance of Clostridium sensu strictoⅠand mesenteric hypoperfusion may have contributed to NEC in the present case.
基金financially supported by the National Natural Science Foundation of China(42077364)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2018.
文摘Polystyrene nanoplastics(PS-NPs)and 3,3′,4,4′-tetrachlorobiphenyl(PCB77)are common pollutants in freshwater aquatic environments.To investigate the separate and combined toxicity of these two pollutants on the freshwater blunt snout bream(Megalobrama amblycephala),270 juveniles were randomly assigned to six exposure treatments:the control group,CT(free of PS-NPs and PCB77),three single exposure groups,PS-L(0.2 mg/L PS-NPs),PS-H(2 mg/L PS-NPs),PCB(0.01 mg/L PCB77),and two combined exposure groups,PP-L(0.2 mg/L PS-NPs+0.01 mg/L PCB77)and PP-H(2 mg/L PS-NPs+0.01 mg/L PCB77).After a seven-day exposure,the tissue histopathology,antioxidant capacity,inflammatory response,and gut microbiome composition of fish were analyzed.The results showed that tissue fluorescence intensity of PS-NPs increases as the exposure levels of PS-NPs increase,and the combined exposure groups exhibited higher fluorescence intensity compared to their single PS-NPs exposure groups.Histopathological analysis showed that the exposure groups exhibited varying degrees of damage to the intestinal tissue compared to the control group,with more severe damage observed in the combined exposure groups.Additionally,liver damage was evident in the PS-H,PP-L and PP-H groups.Furthermore,the highest catalase(CAT)activities and malondialdehyde(MDA)contents were found in the intestine and liver of fish in the PP-L and PP-H groups.The mRNA levels of inflammatory factors(il,il-1β,il-8,il-6,il-10,and tnf-α)were up-regulated in the PS-H,PP-L and PP-H groups compared to those of the CT group.In addition,remarkable alternations in the intestinal microbiome compositions were observed among the groups:the abundance of Verrucomicrobiome and Planctomycetota increased in all exposed groups compared to that of the control group,while the abundance of Actinobacteriota was significantly reduced in the exposure groups.Functional prediction of microbiota indicated that the amino acid and carbohydrate metabolism,as well as intestinal structure,were impaired in the PS-NPs and PCB77 exposure groups.The results suggested that the toxicity of PS-NPs on M.amblycephala including tissue injury,oxidative stress,and disturbance of intestinal microbiota,depends not only on concentration but also increases when co-exposed to PCB77.This finding raises concerns about the ecological safety in freshwater aquatic environments.
文摘The onset and progression of type 2 diabetes mellitus(T2DM)are strongly associated with imbalances in gut bacteria,making the gut microbiome a new potential therapeutic focus.This commentary examines the recent publication in World Journal of Diabetes.The article explores the association between T2DM and gut microbiota,with a focus on the pathophysiological changes related to dysbiosis.It proposes innovative microbiome-targeted therapeutic strategies and evaluates the challenges and future directions of such approaches.This editorial summarizes the key points of their discussion of the role of the gut microbiome in T2DM and elaborates on the influence of specific gut microbial species on the disease through the host–microbiota metabolic axis.It provides new insights for future research on gut-microbiota-based interventions for T2DM.
基金funding by National Natural Science Foundation of China(No.82174492)National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Project(N o.ZJJBGS2024002-1).
文摘Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.
基金supported by the National Natural Science Foundation of China(81973837)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2021A016)National Key projects for international cooperation on science,technology and innovation(2021YFE0201100).
文摘Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic reactions in the body.Evidence suggests that intestinal stem cells(ISCs),which are phenotypic precursors of various intestinal epithelial cells,play a significant role in the regulation of intestinal barrier function and homeostasis.The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs.As a result,the effects exerted by dietary factors,intestinal microbiomes,and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed.This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota,related metabolites,and ISCs,with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body.Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.
基金Binational Science Foundation(BSF)grant number 2015077German Israeli Science Foundation(GIF)grant I-63-410.20-2017,Israeli Science Foundation(ISF)grant 1085/18,and Core Fund Form Tel-Aviv University.
文摘The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.
基金the Guangxi Science and Technology Major Project(No.AA17204095-8)the Open Fund of Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture(No.GXKEYLA2019-05)the China-ASEAN Maritime Cooperation Fund(No.CAMC-2018F)。
文摘Although intestinal fungi play important roles in host health and disease,the composition and diversity of fungal communities remain poorly reported in fish.In this study,fungi in the fore-,mid-,and hindintestine of tilapia(Oreochromis mossambicus)and bighead carp(Aristichthys nobilis)from Hongchaojiang Reservoir in Guangxi,China were investigated by ITS sequencing.Based on this,we obtained 1763478 high-quality tags,which clustered into 1089 operational taxonomic units(OTUs).In total,404 OTUs were annotated,of which 310,68,and 26 belonged to Ascomycota,Basidiomycota,and other,respectively.Results show significant differences in the community composition of intestinal fungi between tilapia and bighead carp but not within their different intestinal segments.Furthermore,154 of the 404 annotated OTUs were considered reliable and were classified into three trophic modes and nine guilds.The three trophic modes consisted of 108 OTUs of saprotrophic fungi,41 OTUs of pathotrophic fungi,and five OTUs of symbiotrophic fungi.The top three most abundant OTUs overall(i.e.,Otu000002,Scopulariopsis acremonium;Otu000018,Alternaria palandui;Otu000034,Aureobasidium pullulans)showed lower abundance in the hind-intestinal segments of bighead carp,suggesting uneven distribution of these fungi in this species.In addition,saprotrophic and pathotrophic fungi were markedly decreased in the hindintestine.It is indicated that the fungal community was not only related to host species specificity but also to the respective physiological functions of different intestinal segments.These findings provide valuable information on the composition,structure,and potential function of the intestinal fungi community associated with different intestinal segments in tilapia and bighead carp under natural conditions,thus highlighting the importance of fungi as an integral part of the inte stinal microbiota in maintaining host health.
基金National Institutes of Health grants,T32AA013527,R01GM128242,and F30DK123929 supported this work.
文摘Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbiome and short-chain fatty acids(SCFAs)following alcohol intoxication and burn injury and to determine whether these changes are associated with intestinal inflammation.Methods 10–12-week-old C57BL/6 male and female mice were subjected to ethanol intoxication and a 12.5%total body surface area scald burn injury.The following day,mice were euthanised and faecal contents from the caecum and small intestine(SI)were harvested for 16S sequencing for microbial analysis and caecum contents underwent high-performance liquid chromatography mass spectroscopy to assess SCFAs.Results The intestinal microbiome of ethanol burn(EB)mice exhibited decreased alpha diversity and distinct beta diversity compared with sham vehicle(SV).EB faeces were marked by increased Proteobacteria and many pathobionts.EB caecum faeces exhibited a significant decrease in butyrate and a downward trend in acetate and total SCFAs.SCFA changes correlated with microbial changes particularly in the SI.Treatment of murine duodenal cell clone-K(MODE-K)cells with faecal slurries led to upregulation of interleukin-6(IL-6)from EB faeces compared with SV faeces which correlated with levels of Enterobacteriaceae.However,supplementation of butyrate reduced faecal slurry-induced MODE-K cells IL-6 release.Conclusion Together,these findings suggest that alcohol and burn injury induce bacterial dysbiosis and a decrease in SCFAs,which together can promote intestinal inflammation and barrier disruption,predisposing to postinjury pathology.
基金supported by“Qishan Scholar”Scientific Research Fund from Fuzhou University,China(GXRC21049)Fujian Provincial Department of Science and Technology,China(2020R1032004)+1 种基金“Elite talent”Project from Fujian Academy of Agricultural Sciences,China(YC20210007)Metabolomics analysis was assisted by Biotree Biotech Co.,Ltd.(Shanghai,China).
文摘Monascus-fermented red mold rice(RMR)has excellent physiological efficacy on lipid metabolism and liver function.This study investigated the ameliorative effects of monascin(MS)from RMR on alcoholic liver injury(ALI)in mice,and further illustrated its mechanism of action.Results indicated that dietary MS intervention obviously ameliorated lipid metabolism and liver function in mice with over-drinking.In addition,MS intervention alleviated alcohol-induced oxidative stress in the liver by reducing the hepatic activities of lactate dehydrogenase(LDH)and hepatic levels of malondialdehyde(MDA),increasing the hepatic activities of catalase(CAT),superoxide dismutase(SOD),alcohol dehydrogenase(ADH)and hepatic levels of glutathione(GSH).16S rRNA amplicon sequencing showed that excessive drinking had a significant effect on the composition of the gut microbiota in mice.MS intervention was beneficial to ameliorate intestinal microbiota dysbiosis by elevating the proportion of Lactobacillus,Lachnospiraceae_UCG-006,Coriobacteriales,etc.,but decreasing the proportion of Staphylococcus,Muribaculaceae,Desulfovibrionaceae,etc.Additionally,correlation analysis indicated that the key intestinal bacterial taxa intervened by MS were closely related to some biochemical indicators of lipid metabolism,liver function and oxidative stress.Moreover,liver metabolomics analysis revealed that dietary MS supplementation significantly regulated the levels of liver metabolites involved in taurine and hypotaurine metabolism,riboflavin metabolism,and purine metabolism,etc.Furthermore,MS intervention regulated gene transcription and protein expression associated with lipid metabolism and oxidative stress in the liver.In short,these findings suggest that MS mitigates alcohol-induced hepatic oxidative damage through modulating the intestinal microbiome and liver metabolic pathway,and thus can be served as a functional component to prevent alcoholic liver disease.
文摘The incidence and prevalence of asthma have increased remarkably in recent years.There are lots of factors contributing to the occurrence and development of asthma.With the improvement of sequencing technology,it has been found that the microbiome plays an important role in the formation of asthma in early life.The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention.The environmental microbiome influences the occurrence of asthma by shaping the human microbiome.The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells(special Tregs).Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life,which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis.It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma.This review aims to summarize the recent advances in the research of microbiome,its relationship with asthma,and the possible mechanism of the microbiome in the occurrence and development of asthma.The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy.However,further study of"when and how"to regulate microbiome is still needed.
基金This study was supported by the USA National Institutes of Health(NIH)grant R01 AA020703,and by Award Number I01BX002213 from the Biomedical Laboratory Research&Development Service of the VA Office of Research and Development to B.Schnab.
文摘Intestinal bacteria contribute to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Recently developed microbial profiling techniques are beginning to shed light on the nature of the changes in the gut microbiota that accompany NAFLD and non-alcoholic steatohepatitis(NASH).In this review,we summarize the role of gut microbiota in the development of NAFLD,NASH,and hepatocellular carcinoma(HCC).We highlight the mechanisms by which gut microbiota contribute to NAFLD/NASH,including through alterations in gut epithelial permeability,choline metabolism,endogenous alcohol production,release of inflammatory cytokines,regulation of hepatic Toll-like receptor(TLR),and bile acid metabolism.In addition,we analyze possible mechanisms for enhanced hepatic carcinogenesis,including alterations in bile acid metabolism,release of inflammatory cytokines,and expression of TLR-4.Finally,we describe therapeutic approaches for NAFLD/NASH and preventive strategies for HCC involving modulation of the intestinal microbiota or affected host pathways.Although recent studies have provided useful information,large-scale prospective studies are required to better characterize the intestinal microbiota and metabolome,in order to demonstrate a causative role for changes in the gut microbiota in the etiology of NAFLD/NASH,to identify new therapeutic strategies for NAFLD/NASH,and to develop more effective methods of preventing HCC.
基金supported by 2014‘‘PUMC Distinguished Professorship"research grant from Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)the Talent Recruitment Program from Institute of Laboratory Animal Sciences,CAMS and Comparative Medicine Center,PUMC,Beijing,China
文摘Systemic autoimmune diseases are a genetic and environmental factors. Although group of heterogeneous disorders caused by both numerous causal genes have been identified by genome-wide association studies （GWAS）, these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogen- esis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body＇s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing （NGS） technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.
