Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut mi...Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.展开更多
Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massiv...Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.展开更多
AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice we...AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.展开更多
The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome ca...The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes(e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.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
Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption...Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment.展开更多
Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide(WIP) was isolated and identified from the sclerotium of...Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide(WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a(1-3)-β-D-glucan with an average Mw of 4.486 × 10~6 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16 S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.展开更多
In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal eco...In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.展开更多
BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFL...BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value <0.01. RESULTS: NAFLD patients harbored lower gut microbiota diversity than healthy subjects did. In comparison to the control group, the Proteobacteria (13.50%) and Fusobacteria (2.76%) phyla were more abundant in NAFLD patients. Additionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, P<0.01). The phylum Bacteroidetes (44.63%) also tended to be more abundant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepatitis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the corresponding Lachnospiraceae family (24.33% vs 14.21%; P<0.01). Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%; P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. The increased level of the genus Blautia, the fami展开更多
Alzheimer＇s disease （AD） is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including ...Alzheimer＇s disease （AD） is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention and diet can induce alterations of gut microbiota and gut physiology and also host cognitive behavior, increasing or decreasing risks of AD. The increased permeability of intestine and blood-brain barrier induced by gut rnicrobiota disturbance will increase the incidence of neurodegeneration disorders. Gut microbial metabolites and their effects on host neurochemical changes may increase or decrease the risk of AD. Pathogenic microbes infection will also increase the risk of AD, and meanwhile, the onset of AD support the ＂hygiene hypothesis＂. All the results suggest that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention will probably become a new treatment for AD.展开更多
Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) play...Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.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
Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic ba...Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.展开更多
Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobio...Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization.Animals used as models of human diseases can be maintained in sterile conditions(isolators used for germ-free rearing)and specifically colonized with defined microbes(including non-cultivable commensal bacteria).The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models.Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia(i.e.,using models of human inflammatory bowel disease and colorectal carcinoma).In contrast,a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic(NOD)mice.Interestingly,the development of atherosclerosis in germ-free apolipoprotein E(ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals.Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota.Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial,disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components(e.g.,probiotics and prebiotics)whose administration may aid in disease prevention and treatment.展开更多
AIM： To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response...AIM： To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/ reperfusion injury. METHODS： Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups： control group （sham shock n = 5） and experimental group （n = 42）. Experimental group was further divided into six groups （n = 7 each） according to different time points after the hemorrhagic shock, including 0^th group, 1^st group, 3^rd group, 6th h group, 12^th group and 24^th group. All the rats were gavaged with 2 mL of suspension of lactulose （L） （100 mg/2 mL） and mannitol （M） （50 mg/each） at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides （LPS） from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument.RESULTS： After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0th h, and it became more serious at the 1^stand the 3^rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6 展开更多
文摘Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.
基金Supported by the National Natural Science Foundation of China,No.81760120 and No.81960128the Key Program of Science and Technology Department of Jiangxi Province,No.20171BBG70084 and No.20192ACBL20037.
文摘Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.
基金the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491,No.81470840 and No.31400001100 Talents Program,No.XBR2011007h
文摘AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
基金Supported by Inserm and Universitéd’Auvergne(UMR 1071)INRA(USC-2018)+1 种基金grants from“Conseil regional d’Auvergne”“Nuovo Soldati Foundation for Cancer Research”and“Fondation pour la recherche médicale”
文摘The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes(e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.
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.
基金Supported by JSPS[Grant-in-Aid for Scientific Research(C)](to Miura K)
文摘Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment.
基金supported by the National Key R&D program of China(No.2018YFD0400203)the Strategic Biological Resources Service Network programme of CAS and Key Research Program of the Chinese Academy of Sciences(No.KFZD-SW-219)the Youth Innovation Promotion Association of CAS(No.2014074)
文摘Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide(WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a(1-3)-β-D-glucan with an average Mw of 4.486 × 10~6 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16 S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
文摘In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.
基金supported by grants from the National Key Basic Research Project(2012CB517501)the Chinese Foundation for Hepatitis Prevention and Control--“Wang Bao-En” Liver Fibrosis Research Foundation(XJS20120501)the National Natural Science Foundation of China(81400610)
文摘BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value <0.01. RESULTS: NAFLD patients harbored lower gut microbiota diversity than healthy subjects did. In comparison to the control group, the Proteobacteria (13.50%) and Fusobacteria (2.76%) phyla were more abundant in NAFLD patients. Additionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, P<0.01). The phylum Bacteroidetes (44.63%) also tended to be more abundant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepatitis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the corresponding Lachnospiraceae family (24.33% vs 14.21%; P<0.01). Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%; P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. The increased level of the genus Blautia, the fami
文摘Alzheimer＇s disease （AD） is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention and diet can induce alterations of gut microbiota and gut physiology and also host cognitive behavior, increasing or decreasing risks of AD. The increased permeability of intestine and blood-brain barrier induced by gut rnicrobiota disturbance will increase the incidence of neurodegeneration disorders. Gut microbial metabolites and their effects on host neurochemical changes may increase or decrease the risk of AD. Pathogenic microbes infection will also increase the risk of AD, and meanwhile, the onset of AD support the ＂hygiene hypothesis＂. All the results suggest that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention will probably become a new treatment for AD.
基金Supported by NIAAA Grants No. AA017729Supported by NIAAA Grants No. AA011576
文摘Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.
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.
文摘Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.
基金grants from the Czech Science Foundation(nos.303/08/0367,303/09/0449,310/07/014,305/08/0535,310/09/1640 and 310/08/H077)the Grant Agency of the Academy of Sciences of the Czech Republic(nos.IAA500200910,IAA500200710,KJB500200904,IAA500200917 and A500200709)+3 种基金the Ministry of Education,Youth and Sports of the Czech Republic(nos.2B06053,2B06155 and MSM 0021620812)the Ministry of Health of the Czech Republic(nos.NS/9775-4,NS/10054-3 and NS/10340-3)EU Project Marie Curie CT 215553,EU Project IPODD consortium(202020)the Institutional Research Concept AV0Z50200510.
文摘Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization.Animals used as models of human diseases can be maintained in sterile conditions(isolators used for germ-free rearing)and specifically colonized with defined microbes(including non-cultivable commensal bacteria).The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models.Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia(i.e.,using models of human inflammatory bowel disease and colorectal carcinoma).In contrast,a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic(NOD)mice.Interestingly,the development of atherosclerosis in germ-free apolipoprotein E(ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals.Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota.Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial,disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components(e.g.,probiotics and prebiotics)whose administration may aid in disease prevention and treatment.
基金Supported by the Grants from the Health Research Foundation (A2003189) and the Science Research Project (2004B30601001) of Guangdong Province, China
文摘AIM： To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/ reperfusion injury. METHODS： Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups： control group （sham shock n = 5） and experimental group （n = 42）. Experimental group was further divided into six groups （n = 7 each） according to different time points after the hemorrhagic shock, including 0^th group, 1^st group, 3^rd group, 6th h group, 12^th group and 24^th group. All the rats were gavaged with 2 mL of suspension of lactulose （L） （100 mg/2 mL） and mannitol （M） （50 mg/each） at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides （LPS） from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument.RESULTS： After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0th h, and it became more serious at the 1^stand the 3^rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6
