Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influen...Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influenced by diet,mainly due to the rich TMAO precursors in diet.However,it was still unclear that the effects of different proportion and source of macronutrients in different dietary pattern on the production process of TMAO.Here,the generation of TMA from precursors and TMAO from TMA was determined after single oral choline chloride and intraperitoneal injection TMA,respectively,in mice fed with carbohydrates,proteins and fats in different proportion and sources.The results suggested that the generation of TMAO was increased by low non-meat protein and high fat via enhancing the production of TMAO from TMA,and decreased by plant protein and refined sugar via reducing TMA production from precursors in gut and TMAO transformation from TMA in liver.The high fat and high sugar diets accelerating the development of atherosclerosis did not increase the production of TMAO,the risk factor for atherosclerosis,which indicated that the dietary compositions rather than the elevated TMAO level might be a more key risk factor for atherosclerosis.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the p...BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.展开更多
Trimethylamine N-oxide(TMAO)is one of the most important nutrients for bacteria in the deep-sea environment and is capable of improving pressure tolerance of certain bacterial strains.To assess the impact of TMAO on m...Trimethylamine N-oxide(TMAO)is one of the most important nutrients for bacteria in the deep-sea environment and is capable of improving pressure tolerance of certain bacterial strains.To assess the impact of TMAO on marine microorganisms,especially those dwelling in the deep-sea environment,we analyzed the bacterial community structure of deep-sea sediments after incubated under different conditions.Enrichments at 50 MPa and 0.1 MPa revealed that TMAO imposed a greater influence on bacterial diversity and community composition at atmospheric pressure condition than that under high hydrostatic pressure(HHP).We found that pressure was the primary factor that determines the bacterial community.Meanwhile,in total,238 bacterial strains were isolated from the enrichments,including 112 strains a ffiliated to 16 genera of 4 phyla from the Yap Trench and 126 strains a ffiliated to 11 genera of 2 phyla from the Mariana Trench.Treatment of HHP reduced both abundance and diversity of isolates,while the presence of TMAO mainly af fected the diversity of isolates obtained.In addition,certain genera were isolated only when TMAO was supplemented.Taken together,we demonstrated that pressure primarily defines the bacterial community and culturable bacterial isolates.Furthermore,we showed for the first time that TMAO had distinct influences on bacterial community depending on the pressure condition.The results enriched the understanding of the significance of TMAO in bacterial adaptation to the deep-sea environment.展开更多
Trimethylamine N-oxide(TMAO) is widely dispersed in marine environments and plays an important role in the biogeochemical cycle of nitrogen. Diverse marine bacteria utilize TMAO as carbon and nitrogen sources or as el...Trimethylamine N-oxide(TMAO) is widely dispersed in marine environments and plays an important role in the biogeochemical cycle of nitrogen. Diverse marine bacteria utilize TMAO as carbon and nitrogen sources or as electron acceptor in anaerobic respiration. Alteration of respiratory component according to the pressure is a common trait of deep-sea bacteria. Deep-sea bacteria from dif ferent genera harbor high hydrostatic pressure(HHP) inducible TMAO reductases that are assumed to be constitutively expressed in the deep-sea piezosphere and facilitating quick reaction to TMAO released from ?sh which is a potential nutrient for bacterial growth. However, whether deep-sea bacteria universally employ this strategy remains unknown. In this study, 237 bacterial strains affliated to 23 genera of Proteobacteria,Bacteroidetes, Firmicutes and Actinobacteria were isolated from seawater, sediment or amphipods collected at dif ferent depths. The pressure tolerance and the utilization of TMAO were examined in 74 strains. The results demonstrated no apparent correlation between the depth where the bacteria inhabit and their pressure tolerance, regarding to our samples. Several deep-sea strains from the genera of Alteromonas, Halomonas,Marinobacter, Photobacterium, and Vibrio showed capacity of TMAO utilization, but none of the isolated Acinebacter, Bacillus, Brevundimonas, Muricauda, Novosphingobium, Rheinheimera, Sphingobium and Stenotrophomonas did, indicating the utilization of TMAO is a species-speci?c feature. Furthermore, we noticed that the ability of TMAO utilization varied among strains of the same species. TMAO has greater impact on the growth of deep-sea isolates of Vibrio neocaledonicus than shallow-water isolates. Taken together, the results describe for the ?rst time the TMAO utilization in deep-sea bacterial strains, and expand our understanding of the physiological characteristic of marine bacteria.展开更多
Sinapine derived from cruciferous plants could be converted into trimethylamine by intestinal microbiota.Its metabolite,trimethylamine N-oxide(TMAO),is closely linked to increased risk of cardiovascular disease and fa...Sinapine derived from cruciferous plants could be converted into trimethylamine by intestinal microbiota.Its metabolite,trimethylamine N-oxide(TMAO),is closely linked to increased risk of cardiovascular disease and fat deposition in mammals.Hens fed with rapeseed meal(RSM)suffered from fatty liver hemorrhage syndrome(FLHS).This study was conducted to investigate whether RSM-induced fatty liver is due to TMAO via altering microbiota composition and diversity.At 33 weeks of age,600 laying hens were randomly divided into 5 treatment groups,namely control and 14%RSM treatment groups(DY5,with 16.2% erucic acid [EA]and 74.66% glucosinolate[Gl]contents;MB1,with 3.50% EA and 43.23 %Gl contents;DY6,with 6.7% EA and 22.67% Gl contents;XH3,with 44.60% EA and 132.83% Gl contents)for 8 weeks.Results revealed that 3 hens died due to liver hemorrhage after ingesting 14% RSM diet.The 14% RSM decreased serum low-density lipoprotein cholesterol(LDL-C)content(P<0.01)while tended to increase serum TMAO content compared to the control group(P=0.08).The 14% RSM diet increased red oil O optical density(P<0.01),and increased total cholesterol(TC)and LDL-C content in the liver(P<0.01,and P<0.01,respectively).The 14%RSM decreased liver total bile acid(TBA)content compared to the control(P<0.01).The DY6 had a higher TBA content in the liver than the XH3(P<0.01).The 14%RSM decreased mRNA abundance of liver X receptors alpha(LXR-α,P=0.01),and increased mRNA abundance of sterol response element binding protein 2(SREBP-2,P=0.04).Results revealed that the in-feed RSM could alter richness and diversity of cecal microbiota compared to the control(P<0.05).Liver TC content and serum TMAO showed a negative relationship with Proteobacteria and Actinobacteria(P=0.04).In conclusion,14%RSM increased liver TC and induced high liver score of FLHS,which was possibly associated with the altered cecal microbiota composition,increased serum TMAO levels and LXR-αand SREBP-2 expressions.展开更多
Background Circulating trimethylamine N-Oxide （TMAO） level has been linked to adverse cardiovascular outcome and mortality in the general population, and atherosclerosis is a window of the cardiovascular disease. Th...Background Circulating trimethylamine N-Oxide （TMAO） level has been linked to adverse cardiovascular outcome and mortality in the general population, and atherosclerosis is a window of the cardiovascular disease. Therefore, the present study was designed to investigate the relationship between TMAO level and atherosclerosis in untreated essential hypertension patients. Methods We measured serum TMAO level in atherosclerosis, subclinical atherosclerosis and controls matched by age and sex. The link between serum TMAO level and CIMT was subsequently assessed. Results The level of serum TMAO was significantly higher in atherosclerosis pa- tients than in controls. Serum TMAO level was positively correlated with carotid intima media thickness （r = 0.783, P 〈 0.001）, and logistic regression indicated that TMAO was a risk factor of atherosclerosis （OR, 1.904; 95% CI, 1.197- 2.733, P 〈 0.001）. Conclusions Serum TMAO concentration positively correlates to carotid intima media thickness, and should be a good predicted biomarker for atherosclerosis.展开更多
基金supported by the National Natural Science Foundation of China(32072145)。
文摘Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influenced by diet,mainly due to the rich TMAO precursors in diet.However,it was still unclear that the effects of different proportion and source of macronutrients in different dietary pattern on the production process of TMAO.Here,the generation of TMA from precursors and TMAO from TMA was determined after single oral choline chloride and intraperitoneal injection TMA,respectively,in mice fed with carbohydrates,proteins and fats in different proportion and sources.The results suggested that the generation of TMAO was increased by low non-meat protein and high fat via enhancing the production of TMAO from TMA,and decreased by plant protein and refined sugar via reducing TMA production from precursors in gut and TMAO transformation from TMA in liver.The high fat and high sugar diets accelerating the development of atherosclerosis did not increase the production of TMAO,the risk factor for atherosclerosis,which indicated that the dietary compositions rather than the elevated TMAO level might be a more key risk factor for atherosclerosis.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
基金Supported by National Key R and D Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565,No.81470840,and No.81800510Shanghai Sailing Program,No.18YF1415900
文摘BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.
基金Supported by the National Natural Science Foundation of China(Nos.91751108,91751202,41806174,41506147)the National Key Research and Development Program of China(Nos.2016YFC0302502,2016YFC0304905,2018YFC0309904)+1 种基金the Sanya Municipal(Nos.2018YD01,2018YD02)the grant for LIA-Mag MC from the Centre National de la Recherche Scientifique
文摘Trimethylamine N-oxide(TMAO)is one of the most important nutrients for bacteria in the deep-sea environment and is capable of improving pressure tolerance of certain bacterial strains.To assess the impact of TMAO on marine microorganisms,especially those dwelling in the deep-sea environment,we analyzed the bacterial community structure of deep-sea sediments after incubated under different conditions.Enrichments at 50 MPa and 0.1 MPa revealed that TMAO imposed a greater influence on bacterial diversity and community composition at atmospheric pressure condition than that under high hydrostatic pressure(HHP).We found that pressure was the primary factor that determines the bacterial community.Meanwhile,in total,238 bacterial strains were isolated from the enrichments,including 112 strains a ffiliated to 16 genera of 4 phyla from the Yap Trench and 126 strains a ffiliated to 11 genera of 2 phyla from the Mariana Trench.Treatment of HHP reduced both abundance and diversity of isolates,while the presence of TMAO mainly af fected the diversity of isolates obtained.In addition,certain genera were isolated only when TMAO was supplemented.Taken together,we demonstrated that pressure primarily defines the bacterial community and culturable bacterial isolates.Furthermore,we showed for the first time that TMAO had distinct influences on bacterial community depending on the pressure condition.The results enriched the understanding of the significance of TMAO in bacterial adaptation to the deep-sea environment.
基金Supported by the National Natural Science Foundation of China(Nos.41506147,91751108)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB06010203)+3 种基金the Key Research and Development Program of Hainan Province(No.ZDYF2016211)the Natural Science Foundation of Hainan Province(No.20163151)the Sanya City(No.2016PT18)a grant for LIA-MagMC from the Centre National de la Recherche Scientifique
文摘Trimethylamine N-oxide(TMAO) is widely dispersed in marine environments and plays an important role in the biogeochemical cycle of nitrogen. Diverse marine bacteria utilize TMAO as carbon and nitrogen sources or as electron acceptor in anaerobic respiration. Alteration of respiratory component according to the pressure is a common trait of deep-sea bacteria. Deep-sea bacteria from dif ferent genera harbor high hydrostatic pressure(HHP) inducible TMAO reductases that are assumed to be constitutively expressed in the deep-sea piezosphere and facilitating quick reaction to TMAO released from ?sh which is a potential nutrient for bacterial growth. However, whether deep-sea bacteria universally employ this strategy remains unknown. In this study, 237 bacterial strains affliated to 23 genera of Proteobacteria,Bacteroidetes, Firmicutes and Actinobacteria were isolated from seawater, sediment or amphipods collected at dif ferent depths. The pressure tolerance and the utilization of TMAO were examined in 74 strains. The results demonstrated no apparent correlation between the depth where the bacteria inhabit and their pressure tolerance, regarding to our samples. Several deep-sea strains from the genera of Alteromonas, Halomonas,Marinobacter, Photobacterium, and Vibrio showed capacity of TMAO utilization, but none of the isolated Acinebacter, Bacillus, Brevundimonas, Muricauda, Novosphingobium, Rheinheimera, Sphingobium and Stenotrophomonas did, indicating the utilization of TMAO is a species-speci?c feature. Furthermore, we noticed that the ability of TMAO utilization varied among strains of the same species. TMAO has greater impact on the growth of deep-sea isolates of Vibrio neocaledonicus than shallow-water isolates. Taken together, the results describe for the ?rst time the TMAO utilization in deep-sea bacterial strains, and expand our understanding of the physiological characteristic of marine bacteria.
基金fanatically supported by National Science and Technology Project(2014BAD13B04)the Sichuan Provincial Science and Technology project(2018NZ20009,2014NZ0043)。
文摘Sinapine derived from cruciferous plants could be converted into trimethylamine by intestinal microbiota.Its metabolite,trimethylamine N-oxide(TMAO),is closely linked to increased risk of cardiovascular disease and fat deposition in mammals.Hens fed with rapeseed meal(RSM)suffered from fatty liver hemorrhage syndrome(FLHS).This study was conducted to investigate whether RSM-induced fatty liver is due to TMAO via altering microbiota composition and diversity.At 33 weeks of age,600 laying hens were randomly divided into 5 treatment groups,namely control and 14%RSM treatment groups(DY5,with 16.2% erucic acid [EA]and 74.66% glucosinolate[Gl]contents;MB1,with 3.50% EA and 43.23 %Gl contents;DY6,with 6.7% EA and 22.67% Gl contents;XH3,with 44.60% EA and 132.83% Gl contents)for 8 weeks.Results revealed that 3 hens died due to liver hemorrhage after ingesting 14% RSM diet.The 14% RSM decreased serum low-density lipoprotein cholesterol(LDL-C)content(P<0.01)while tended to increase serum TMAO content compared to the control group(P=0.08).The 14% RSM diet increased red oil O optical density(P<0.01),and increased total cholesterol(TC)and LDL-C content in the liver(P<0.01,and P<0.01,respectively).The 14%RSM decreased liver total bile acid(TBA)content compared to the control(P<0.01).The DY6 had a higher TBA content in the liver than the XH3(P<0.01).The 14%RSM decreased mRNA abundance of liver X receptors alpha(LXR-α,P=0.01),and increased mRNA abundance of sterol response element binding protein 2(SREBP-2,P=0.04).Results revealed that the in-feed RSM could alter richness and diversity of cecal microbiota compared to the control(P<0.05).Liver TC content and serum TMAO showed a negative relationship with Proteobacteria and Actinobacteria(P=0.04).In conclusion,14%RSM increased liver TC and induced high liver score of FLHS,which was possibly associated with the altered cecal microbiota composition,increased serum TMAO levels and LXR-αand SREBP-2 expressions.
基金supported by the grants from Guangdong Natural Science Foundation(No.2015A030313660)Technology Project Foundation of Guangzhou(No.2014y2-00140/No.1563000381/No.201604020018,/No.201604020186)+1 种基金Technology Project Foundation of Guangdong Province(No.2014B020212008)National Natural Science Foundation of China(No.81300230)
文摘Background Circulating trimethylamine N-Oxide （TMAO） level has been linked to adverse cardiovascular outcome and mortality in the general population, and atherosclerosis is a window of the cardiovascular disease. Therefore, the present study was designed to investigate the relationship between TMAO level and atherosclerosis in untreated essential hypertension patients. Methods We measured serum TMAO level in atherosclerosis, subclinical atherosclerosis and controls matched by age and sex. The link between serum TMAO level and CIMT was subsequently assessed. Results The level of serum TMAO was significantly higher in atherosclerosis pa- tients than in controls. Serum TMAO level was positively correlated with carotid intima media thickness （r = 0.783, P 〈 0.001）, and logistic regression indicated that TMAO was a risk factor of atherosclerosis （OR, 1.904; 95% CI, 1.197- 2.733, P 〈 0.001）. Conclusions Serum TMAO concentration positively correlates to carotid intima media thickness, and should be a good predicted biomarker for atherosclerosis.
