Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood.We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with p...Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood.We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2(PCV2)and Campylobacter.Campylobacter infection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacter and Enterobacteriaceae,whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets,PCV2 and Campylobacter infection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community,and specially Campylobacter performed as a module hub in ecological networks.The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids,following by a higher pH level in colon cavity.Campylobacter infection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1,occluding,and zonula occludens protein-1 genes,and PCV2 infection induced intestinal inflammation together with a higher permeability of colon.Generally,these results suggested that PCV2 and Campylobacter infection could induce microbial dysbiosis and metabolic dysfunction,and cause intestinal disorder,all of which finally were associated to contribute to the diarrhea of early-weaning piglets.展开更多
Research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significa...Research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significance to routinely acquire the status of the human gut microbiota;however,there is no method to evaluate the gut microbiome through small amounts of fecal microbes.In this study,we found ten predominant groups of gut bacteria that characterized the whole microbiome in the human gut from a large-sample Chinese cohort,constructed a real-time quantitative polymerase chain reaction(qPCR)method and developed a set of analytical approaches to detect these ten groups of predominant gut bacterial species with great maneuverability,efficiency,and quantitative features.Reference ranges for the ten predominant gut bacterial groups were established,and we found that the concentration and pairwise ratios of the ten predominant gut bacterial groups varied with age,indicating gut microbial dysbiosis.By comparing the detection results of liver cirrhosis(LC)patients with those of healthy control subjects,differences were then analyzed,and a classification model for the two groups was built by machine learning.Among the six established classification models,the model established by using the random forest algorithm achieved the highest area under the curve(AUC)value and sensitivity for predicting LC.This research enables easy,rapid,stable,and reliable testing and evaluation of the balance of the gut microbiota in the human body,which may contribute to clinical work.展开更多
Background:Inflammatory bowel disease(IBD),comprising Crohn's disease(CD)and ulcerative colitis(UC),is a heterogeneous state of chronic intestinal inflammation.Intestinal innate immunity,including innate immune ce...Background:Inflammatory bowel disease(IBD),comprising Crohn's disease(CD)and ulcerative colitis(UC),is a heterogeneous state of chronic intestinal inflammation.Intestinal innate immunity,including innate immune cells,defends against pathogens and excessive entry of gut microbiota,while preserving immune tolerance to resident intestinal microbiota,and may be characterized by its capacity to produce a rapid and nonspecific reaction.The association between microbiota dysbiosis and the pathogenesis of IBD is complex and dynamic.When the intestinal ecosystem is in dysbiosis,the reduced abundance and diversity of intestinal gut microbiota make the host more vulnerable to the attack of exogenous and endogenous pathogenic gut microbiota.The aim of our study was to comprehensively assess the relationship between microbial populations within UC,the signaling pathways of pathogenic gut microbe therein and the inflammatory response,as well as to understand the effects of using PE&AFWE(poppy extract[Papaver nudicaule L.]and Artemisia frigida Willd.extract)on UC modulation.Methods:A UC mouse model was established by inducing SPF-grade C57BL/6 mice using dextrose sodium sulfate(DSS).Based on metagenomic sequencing to characterize the gut microbiome,the relationship between gut microbiota dysbiosis and gut microbiota was further studied using random forest and Bayesian network analysis methods,as well as histopathological analysis.Results:(1)We found that the 5 gut microbiota with the highest relative abundance of inflammatory bowel disease UC model gut microbiota were consistent with the top 5 ranked natural bacteria.There were three types of abundance changes in the model groups:increases(Chlamydiae/Proteobacteria and Deferribacteres),decreases(Firmicutes),and no significant changes(Bacteroidetes).The UC model group was significantly different from the control group,with 1308 differentially expressed species with abundance changes greater than or equal to 2-fold.(2)The proportion of the fecal flora in the UC group decreased by 37.5%in the Firmicutes and increased by 14.29%in the proportion of Proteobacteria compared to the control group before treatment.(3)The significantly enriched and increased signaling pathways screened were the'arachidonic acid metabolic pathway'and the'phagosomal pathway',which both showed a decreasing trend after drug administration.(4)Based on the causal relationship between different OTUs and the UC model/PE&AFWE administration,screening for directly relevant OTU networks,the UC group was found to directly affect OTU69,followed by a cascade of effects on OTU12,OTU121,OTU93,and OTU7,which may be the pathway of action that initiated the pathological changes in normal mice.(5)We identified a causal relationship between common differentially expressed OTUs and PE&AFWE and UC in the pre-and post-PE&AFWE-treated groups.Thereby,we learned that PE&AFWE can directly affect OTU90,after which it inhibits UC,inhibiting the activity of arachidonic acid metabolic pathway by affecting OTU118,which in turn inhibits the colonization of gut microbiota by OTU93 and OTU7.(6)Histopathological observation and scoring(HS)of the colon showed that there was a significant difference between the model group and the control group(p<0.001),and that there was a significant recovery in both the sulfasalazine(SASP)and the PE&AFWE groups after the administration of the drug(p<0.0001).Conclusion:We demonstrated causal effects and inflammatory metabolic pathways in gut microbiota dysbiosis and IBD,with five opportunistic pathogens directly contributing to IBD.PE&AFWE reduced the abundance of proteobacteria in the gut microbiota,and histopathology showed significant improvement.展开更多
Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D ma...Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.展开更多
The gut microbiota(GM)plays a role in the development and progression of type 1 and type 2 diabetes mellitus(DM)and its complications.Gut dysbiosis contributes to the pathogenesis of DM.The GM has been shown to influe...The gut microbiota(GM)plays a role in the development and progression of type 1 and type 2 diabetes mellitus(DM)and its complications.Gut dysbiosis contributes to the pathogenesis of DM.The GM has been shown to influence the efficacy of different antidiabetic medications.Intake of gut biotics,like prebiotics,probiotics and synbiotics,can improve the glucose control as well as the metabolic profile associated with DM.There is some preliminary evidence that it might even help with the cardiovascular,ophthalmic,nervous,and renal complications of DM and even contribute to the prevention of DM.More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.展开更多
The intestinal microbiota has a symbiotic relationship with humans. It participates in some important physiological activities in the human body and has an important impact on human health. It has become a hot topic o...The intestinal microbiota has a symbiotic relationship with humans. It participates in some important physiological activities in the human body and has an important impact on human health. It has become a hot topic of research by scientists in recent years. Among them, the research on the correlation </span><span style="font-family:Verdana;">between intestinal microbiota and cancer has increased rapidly. At present, the incidence rate of breast cancer is increasing, which seriously endangers the health of women. More and more studies have found that the occurrence of breast cancer is related to intestinal microbiota, and its possible mechanism inc</span><span style="font-family:Verdana;">ludes intestinal microbiota dysbiosis, estrogen metabolism changes, immun</span><span style="font-family:Verdana;">e regulation, and the participation of intestinal microbiota metabolites, etc. With the further development of high-throughput sequencing technology, th</span><span style="font-family:Verdana;">e research on the correlation between intestinal microbiota and breast cancer</span><span style="font-family:Verdana;"> has become more in-depth, from a structural level confined to microorganisms to a more comprehensive system structure and function level. These research results provide a new research direction for the treatment of breast cancer. In order to further study the interaction between intestinal microbes and breast cancer, this </span><span style="font-family:Verdana;">article will comprehensively describe the intestinal microbiota and breast cancer from four aspects: intestinal microbial dysbiosis, altered estrogen metabolism, immune regulation, and intestinal microbial metabolites. It also reviews the application research of intestinal microbiota in breast cancer treatment, including the influence of intestinal microbiota on the effects of breast cancer radiotherapy and chemotherapy, probiotic therapy, and dietotherapy.展开更多
Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis.They exert robust pro-inflammatory effects and recruit other immune cells in the acute p...Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis.They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation,but paradoxically,they also limit exogenousmicrobial invasion and facilitate mucosal restoration.Hyperactivation or dysfunction of neutrophils results in abnormal immune responses,leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus,rheumatoid arthritis,and inflammatory bowel diseases(IBD).As a refractory intestinal inflammatory disease,the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved.However,the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood.Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis,aggravated intestinal architectural damage,compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD.Paradoxically,activated neutrophils are also associated with effective elimination of invaded microbiota,promoted angiogenesis and tissue restoration of gutmucosa in IBD.Here,we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinalmucosal inflammation,hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.展开更多
基金supported by National Key R&D Program of China(2016YFD0501201)China Scholarship Council(201806825084)
文摘Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood.We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2(PCV2)and Campylobacter.Campylobacter infection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacter and Enterobacteriaceae,whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets,PCV2 and Campylobacter infection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community,and specially Campylobacter performed as a module hub in ecological networks.The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids,following by a higher pH level in colon cavity.Campylobacter infection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1,occluding,and zonula occludens protein-1 genes,and PCV2 infection induced intestinal inflammation together with a higher permeability of colon.Generally,these results suggested that PCV2 and Campylobacter infection could induce microbial dysbiosis and metabolic dysfunction,and cause intestinal disorder,all of which finally were associated to contribute to the diarrhea of early-weaning piglets.
基金supported by the National Key Research and Development Program of China(2018YFC2000500)the Fundamental Research Funds for the Central Universities(2022ZFJH003)+3 种基金the Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases(2022zz22)the National Natural Science Foundation of China(81703430,32170058,and 82200994)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-045)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022051B)。
文摘Research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significance to routinely acquire the status of the human gut microbiota;however,there is no method to evaluate the gut microbiome through small amounts of fecal microbes.In this study,we found ten predominant groups of gut bacteria that characterized the whole microbiome in the human gut from a large-sample Chinese cohort,constructed a real-time quantitative polymerase chain reaction(qPCR)method and developed a set of analytical approaches to detect these ten groups of predominant gut bacterial species with great maneuverability,efficiency,and quantitative features.Reference ranges for the ten predominant gut bacterial groups were established,and we found that the concentration and pairwise ratios of the ten predominant gut bacterial groups varied with age,indicating gut microbial dysbiosis.By comparing the detection results of liver cirrhosis(LC)patients with those of healthy control subjects,differences were then analyzed,and a classification model for the two groups was built by machine learning.Among the six established classification models,the model established by using the random forest algorithm achieved the highest area under the curve(AUC)value and sensitivity for predicting LC.This research enables easy,rapid,stable,and reliable testing and evaluation of the balance of the gut microbiota in the human body,which may contribute to clinical work.
基金National Natural Science Foundation of ChinaGrant/Award Number:81774449。
文摘Background:Inflammatory bowel disease(IBD),comprising Crohn's disease(CD)and ulcerative colitis(UC),is a heterogeneous state of chronic intestinal inflammation.Intestinal innate immunity,including innate immune cells,defends against pathogens and excessive entry of gut microbiota,while preserving immune tolerance to resident intestinal microbiota,and may be characterized by its capacity to produce a rapid and nonspecific reaction.The association between microbiota dysbiosis and the pathogenesis of IBD is complex and dynamic.When the intestinal ecosystem is in dysbiosis,the reduced abundance and diversity of intestinal gut microbiota make the host more vulnerable to the attack of exogenous and endogenous pathogenic gut microbiota.The aim of our study was to comprehensively assess the relationship between microbial populations within UC,the signaling pathways of pathogenic gut microbe therein and the inflammatory response,as well as to understand the effects of using PE&AFWE(poppy extract[Papaver nudicaule L.]and Artemisia frigida Willd.extract)on UC modulation.Methods:A UC mouse model was established by inducing SPF-grade C57BL/6 mice using dextrose sodium sulfate(DSS).Based on metagenomic sequencing to characterize the gut microbiome,the relationship between gut microbiota dysbiosis and gut microbiota was further studied using random forest and Bayesian network analysis methods,as well as histopathological analysis.Results:(1)We found that the 5 gut microbiota with the highest relative abundance of inflammatory bowel disease UC model gut microbiota were consistent with the top 5 ranked natural bacteria.There were three types of abundance changes in the model groups:increases(Chlamydiae/Proteobacteria and Deferribacteres),decreases(Firmicutes),and no significant changes(Bacteroidetes).The UC model group was significantly different from the control group,with 1308 differentially expressed species with abundance changes greater than or equal to 2-fold.(2)The proportion of the fecal flora in the UC group decreased by 37.5%in the Firmicutes and increased by 14.29%in the proportion of Proteobacteria compared to the control group before treatment.(3)The significantly enriched and increased signaling pathways screened were the'arachidonic acid metabolic pathway'and the'phagosomal pathway',which both showed a decreasing trend after drug administration.(4)Based on the causal relationship between different OTUs and the UC model/PE&AFWE administration,screening for directly relevant OTU networks,the UC group was found to directly affect OTU69,followed by a cascade of effects on OTU12,OTU121,OTU93,and OTU7,which may be the pathway of action that initiated the pathological changes in normal mice.(5)We identified a causal relationship between common differentially expressed OTUs and PE&AFWE and UC in the pre-and post-PE&AFWE-treated groups.Thereby,we learned that PE&AFWE can directly affect OTU90,after which it inhibits UC,inhibiting the activity of arachidonic acid metabolic pathway by affecting OTU118,which in turn inhibits the colonization of gut microbiota by OTU93 and OTU7.(6)Histopathological observation and scoring(HS)of the colon showed that there was a significant difference between the model group and the control group(p<0.001),and that there was a significant recovery in both the sulfasalazine(SASP)and the PE&AFWE groups after the administration of the drug(p<0.0001).Conclusion:We demonstrated causal effects and inflammatory metabolic pathways in gut microbiota dysbiosis and IBD,with five opportunistic pathogens directly contributing to IBD.PE&AFWE reduced the abundance of proteobacteria in the gut microbiota,and histopathology showed significant improvement.
文摘Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.
文摘The gut microbiota(GM)plays a role in the development and progression of type 1 and type 2 diabetes mellitus(DM)and its complications.Gut dysbiosis contributes to the pathogenesis of DM.The GM has been shown to influence the efficacy of different antidiabetic medications.Intake of gut biotics,like prebiotics,probiotics and synbiotics,can improve the glucose control as well as the metabolic profile associated with DM.There is some preliminary evidence that it might even help with the cardiovascular,ophthalmic,nervous,and renal complications of DM and even contribute to the prevention of DM.More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.
文摘The intestinal microbiota has a symbiotic relationship with humans. It participates in some important physiological activities in the human body and has an important impact on human health. It has become a hot topic of research by scientists in recent years. Among them, the research on the correlation </span><span style="font-family:Verdana;">between intestinal microbiota and cancer has increased rapidly. At present, the incidence rate of breast cancer is increasing, which seriously endangers the health of women. More and more studies have found that the occurrence of breast cancer is related to intestinal microbiota, and its possible mechanism inc</span><span style="font-family:Verdana;">ludes intestinal microbiota dysbiosis, estrogen metabolism changes, immun</span><span style="font-family:Verdana;">e regulation, and the participation of intestinal microbiota metabolites, etc. With the further development of high-throughput sequencing technology, th</span><span style="font-family:Verdana;">e research on the correlation between intestinal microbiota and breast cancer</span><span style="font-family:Verdana;"> has become more in-depth, from a structural level confined to microorganisms to a more comprehensive system structure and function level. These research results provide a new research direction for the treatment of breast cancer. In order to further study the interaction between intestinal microbes and breast cancer, this </span><span style="font-family:Verdana;">article will comprehensively describe the intestinal microbiota and breast cancer from four aspects: intestinal microbial dysbiosis, altered estrogen metabolism, immune regulation, and intestinal microbial metabolites. It also reviews the application research of intestinal microbiota in breast cancer treatment, including the influence of intestinal microbiota on the effects of breast cancer radiotherapy and chemotherapy, probiotic therapy, and dietotherapy.
基金This work is supported by the National Natural Science Foundation of China(Grants No.81630017 and 91942312).
文摘Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis.They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation,but paradoxically,they also limit exogenousmicrobial invasion and facilitate mucosal restoration.Hyperactivation or dysfunction of neutrophils results in abnormal immune responses,leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus,rheumatoid arthritis,and inflammatory bowel diseases(IBD).As a refractory intestinal inflammatory disease,the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved.However,the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood.Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis,aggravated intestinal architectural damage,compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD.Paradoxically,activated neutrophils are also associated with effective elimination of invaded microbiota,promoted angiogenesis and tissue restoration of gutmucosa in IBD.Here,we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinalmucosal inflammation,hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.