Fecal microbiota transplantation （FMT） has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host in...Fecal microbiota transplantation （FMT） has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut- brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step- up FMT strategy based on literature and state experts＇ perspectives.展开更多
The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the c...The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development.The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.展开更多
Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literat...Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.展开更多
Macrophages represent a major cell type of innate immunity and have emerged as a critical player and therapeutic target in many chronic inflammatory diseases. Hepatic macrophages consist of Kupffer cells, which are or...Macrophages represent a major cell type of innate immunity and have emerged as a critical player and therapeutic target in many chronic inflammatory diseases. Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. Hepatic macrophages play a central role in maintaining homeostasis of the liver and in the pathogenesis of liver injury, making them an attractive therapeutic target for liver diseases. However, the various populations of hepatic macrophages display different phenotypes and exert distinct functions. Thus, more research is required to better understand these cells to guide the development of macrophage-based therapeutic interventions. This review article will summarize the current knowledge on the origins and composition of hepatic macrophages, their functions in maintaining hepatic homeostasis, and their involvement in both promoting and resolving liver inflammation, injury, and fibrosis. Finally, the current strategies being developed to target hepatic macrophages for the treatment of liver diseases will be reviewed.展开更多
It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial r...It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary factors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.展开更多
Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important ro...Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.展开更多
AIM To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis.METHODS A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were rando...AIM To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis.METHODS A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls(HC), ulcerative colitis model group(UC), UC with 7 d of moxibustion(UC-7), UC with 14 d of moxibustion(UC-14), UC with mesalazine gavage(UC-W), HC with 7 d of moxibustion(HC-7), HC with 14 d of moxibustion(HC-14). Moxibustion was applied to the bilateral Tianshu(ST25). Gut microbiome profiling was conducted by 16 S r RNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term(7 d) but no longer term(14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12(IL-12)(P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, Ig A, tumour necrosis factor-α and its receptors 1(TNFR1) and TNFR2(P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10(P < 0.01) and transforming growth factor-β(P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion.CONCLUSION Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucos展开更多
Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gast...Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.展开更多
The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune c...The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.展开更多
The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyze...The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.展开更多
There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating me...There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.展开更多
Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects c...Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.展开更多
Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The ma...Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.展开更多
Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health a...Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.展开更多
基金This work was supported by publicaUy donated Intestine Initiative Jiangsu Province Medicine Creation Team and Leading Talents project （Faming Zhang） National Natural Science Foundation of China （Grant Nos. 81670495 and 81600417） and National Center for Clinical Research of Digestive System Diseases （2015BAI13B07）.
文摘Fecal microbiota transplantation （FMT） has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut- brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step- up FMT strategy based on literature and state experts＇ perspectives.
基金"PUMC"Fellow award from Peking Union Medical Collage(PUMC)CAMS Initiative for Innovative Medicine(2016-I2M-1-006)
文摘The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development.The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.
基金This study was supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support （No. XMLX201401）, the National Natural Science Foundation of China （No. 81301138）, National High-Tech R＆D Program of China （863 Program, No. 2015AA020514）, National Hundred, Thousand, and Ten Thousand Talents Project of Beijing （No. 2010-005）.
文摘Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.
文摘Macrophages represent a major cell type of innate immunity and have emerged as a critical player and therapeutic target in many chronic inflammatory diseases. Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. Hepatic macrophages play a central role in maintaining homeostasis of the liver and in the pathogenesis of liver injury, making them an attractive therapeutic target for liver diseases. However, the various populations of hepatic macrophages display different phenotypes and exert distinct functions. Thus, more research is required to better understand these cells to guide the development of macrophage-based therapeutic interventions. This review article will summarize the current knowledge on the origins and composition of hepatic macrophages, their functions in maintaining hepatic homeostasis, and their involvement in both promoting and resolving liver inflammation, injury, and fibrosis. Finally, the current strategies being developed to target hepatic macrophages for the treatment of liver diseases will be reviewed.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0800700 and 2018YFC1003200)and the National Natural Science Foundation of the P.R.of China(No.91857115,31925021,and 81921001).
文摘It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary factors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.
基金Supported by NIH KO8 DK093578CCFA Career Development Award 3467(DQS)F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
文摘Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.
基金Supported by National Natural Science Foundation of China,No.81473758National Basic Research Programme of China(973 programme),No.2015CB554500
文摘AIM To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis.METHODS A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls(HC), ulcerative colitis model group(UC), UC with 7 d of moxibustion(UC-7), UC with 14 d of moxibustion(UC-14), UC with mesalazine gavage(UC-W), HC with 7 d of moxibustion(HC-7), HC with 14 d of moxibustion(HC-14). Moxibustion was applied to the bilateral Tianshu(ST25). Gut microbiome profiling was conducted by 16 S r RNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term(7 d) but no longer term(14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12(IL-12)(P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, Ig A, tumour necrosis factor-α and its receptors 1(TNFR1) and TNFR2(P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10(P < 0.01) and transforming growth factor-β(P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion.CONCLUSION Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucos
基金Supported by Comisión Nacional de Investigación Científica y Tecnológica-Fondos de Financiamiento de Centros de Investigación en áreas Prioritarias,No.15130011(to Quest AF)Fondo Nacional de Desarrollo Científico y Tecnológico,No.1170925(to Quest AF)and No.1171615(to Valenzuela MA)Fondo para la Investigación en Odontología Universidad de Chile,No.17/020(to Bravo D)
文摘Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
基金supported in part by the National Natural Science Foundation of China(grants#81830016,81771732,and 81620108002 to X.M.,#81922010 and 81873561 to R.T.)supported in part by services provided by the NIH centers P30 DK120515 and P50 AA011999+1 种基金supported by the excellence initiative VASCage(Centre for Promoting Vascular Health in the Ageing Community)R8fD K-Centre(COMET program-Competence Centers for Excellent Technologies)funded by the Austrian Ministry for Transport,Innovation and Technology,the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol,Salzburg and Vienna.
文摘The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.
基金supported by Future Life Sciences International Ltd.(NSBJ01032014,http://ffsi.jpl)
文摘The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.
基金Supported by National Basic Research Program(973 Program)of China,No.2013CB531403
文摘There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.
文摘Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.
基金Supported by the National Natural Science Foundation of China,No.81620108030
文摘Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.
基金This study was supported by grants from the National Basic Research Program of China （973 Program, 2013CB531401）, the Major Science and Technology Program of Zhejiang Province （2014C03039）, and the Natural Science Foundation of Zhejiang Province （R16H260001）. We acknowledge Doctors Chunlei Chen, Bo Li, Jing Guo, Ding Shi, Qiongling Bao, Silan Gu, Yanfei Chen, Kai Zhou, Qixiang Luo, Ruiqi Tang, and Xiangyang Jiang for the literature search and the preparation for the manuscript. We also thank the reviewers for their thoughtful and helpful comments.
文摘Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.
