Background:Recent studies suggest an association between the expansion of Prevotella copri and the disease severity in children with metabolic dysfunction-associated steatotic liver disease(MASLD).We aimed to investig...Background:Recent studies suggest an association between the expansion of Prevotella copri and the disease severity in children with metabolic dysfunction-associated steatotic liver disease(MASLD).We aimed to investigate the causative role and molecular mechanisms of P.copri in pediatric MASLD.Methods:C57BL/6 J mice aged 3 weeks were fed a high-fat diet(HFD)and orally administered with P.copri for 5 weeks.We assessed the key features of MASLD and the gut microbiota profile.By untargeted metabolomics on mouse fecal samples and the supernatant from P.copri culture,we identified P.copriderived metabolite and tested its effects in vitro.Results:In HFD-fed mice,administration of P.copri significantly promoted liver steatosis.Genes associated with inflammation and fibrosis were significantly upregulated in the livers from the HFD+P.copri group compared with those in the livers from the HFD group.In addition,P.copri reduced gut microbial diversity,increased the proportion of Firmicutes and decreased Bacteroidota.Importantly,5-aminopentanoic acid(5-AVA)was significantly enriched in both mouse feces from the HFD+P.copri group and the culture supernatant of P.copri.In vitro,5-AVA aggravated palmitic acid-induced lipid accumulation in HepG2 cells and primary mouse hepatocytes.Mechanistically,P.copri-produced 5-AVA exacerbated hepatic steatosis by promoting lipogenesis and fatty acid uptake,while also reducing hepatic very-low-density lipoprotein export.Conclusions:Our findings demonstrated that P.copri promotes liver steatosis in HFD-fed juvenile mice through its metabolite 5-AVA,suggesting its potential as a therapeutic target for the management of pediatric MASLD.展开更多
Gut microbiota disruption during the weaning process is a significant factor of intestinal injury.Our previous studies have suggested that Prevotella may play a critical role in causing intestinal inflammation.This st...Gut microbiota disruption during the weaning process is a significant factor of intestinal injury.Our previous studies have suggested that Prevotella may play a critical role in causing intestinal inflammation.This study aimed to clarify the impact of Prevotella copri on intestinal injury and the protecting effect by dihydroquercetin (DHQ) in weaned piglets.A total of 108 healthy Duroc×Landrace×Yorkshire weaned piglets,aged 21 d,were randomly allocated into 3 groups with 6 replicates and 6 piglets per replicate.The piglets were the following diets for 28 d:1) a basal diet,2) basal diet containing1.0×10^(8)CFU/kg P.copri,3) basal diet supplemented with 1.0×10^(8)CFU/kg P.copri and 100 mg/kg DHQ.Results showed that P.copri decreased significantly the average daily gain (ADG)(P<0.001),which was recovered by supplementation of DHQ with decreased serum levels of malondialdehyde (MDA),interleukin (IL)-2 and IL-8 but increased total superoxide dismutase (T-SOD) activity and IL-10 in weaned piglets (P<0.001).Moreover,DHQ increased the expression of tight junction proteins (claudin-2,occludin and tight junction protein zonula occludens protein-1 (ZO-1) and the mRNA expression of glutathione peroxidase 4 (GPX-4) in ileum (P<0.001).Intestinal flora analysis showed that P.copri increased the relative abundance of Prevotella (P=0.026) and Eubacterium coprostanoligenes group(P<0.001),but decreased the relative abundance of Lachnospiraceae NK4A136 group (P<0.001),while supplementation of DHQ reduced the relative abundance of Prevotella (P=0.026).Metabolomics results indicated that P.copri enhanced the content of 12-OH bile acid,but decreased the contents of glycodeoxycholic acid (GDCA) and glycochenodeoxycholic acid (GCDCA)(P<0.001),while DHQ reduced the12-OH bile acid content (P<0.001) and increased the GDCA content (P=0.020).In summary,P.copri caused intestinal injury and reduced growth performance in weaned piglets,and DHQ showed a protective effect by modulating gut microbiota and bile acids metabolism.展开更多
Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P....Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P.copri RA,from the feces of RA patients and showed that colonization of P.copri RA exacerbated arthritis in a collagen-induced arthritis(CIA)model.With the presence of P.copri RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation.Colonization of P.copri together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty acids.Succinate promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA model.Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.展开更多
Prevotella copri and its related taxa are widely detected in mammalian gut microbiomes and have been linked with an enterotype in humans.However,their microevolution and macroevolution among hosts are poorly character...Prevotella copri and its related taxa are widely detected in mammalian gut microbiomes and have been linked with an enterotype in humans.However,their microevolution and macroevolution among hosts are poorly characterized.In this study,extensively collected marker genes and genomes were analyzed to trace their evolutionary history,host specificity,and biogeographic distribution.Investigations based on marker genes and genomes suggest that a P.copri-containing lineage(PCL)harbors diverse species in higher primates.Firstly,P.copri in the human gut consisted of multiple groups exhibiting high genomic divergence and conspicuous but non-strict biogeographic patterns.Most African strains with high genomic divergence from other strains were phylogenetically located at the root of the species,indicating the co-evolutionary history of P.copri and Homo sapiens.Secondly,although long-term co-evolution between PCL and higher primates was revealed,sporadic signals of co-speciation and extensive host jumping of PCL members were suggested among higher primates.Metagenomic and phylogenetic analyses indicated that P.copri and other PCL species found in domesticated mammals had been recently transmitted from humans.Thirdly,strong evidence was found on the extensively horizontal transfer of genes(e.g.,genes encoding carbohydrate-active enzymes)among sympatric P.copri groups and PCL species in the same primate host.Our study provides panoramic insights into the combined effects of vertical and horizontal transmission,as well as potential niche adaptation,on the microevolutionary and macroevolutionary history for an enterotyperepresentative lineage.展开更多
Scanning electron microscopy(SEM)and histological techniques were used to observe and study the structure of setae on the integument surface of the dung beetle Copris ochus Motschulsky and on the foot pad of the gecko...Scanning electron microscopy(SEM)and histological techniques were used to observe and study the structure of setae on the integument surface of the dung beetle Copris ochus Motschulsky and on the foot pad of the gecko Gekko gecko and their relationship to anti-adherent and adherent functions respectively.There are very distinctive comparison between the structures and the constructs of the setae on the dung beetle and the gecko:the setae of the dung beetle are ramification of the integument,mainly distributing on the body abdomen surface and the lateral side of the legs,loosely arranging,having different length with many buds and sticks along the whole seta body but without side branches,uprightly directing to the contacting dung face.The setae of the gecko are protuberances from the skin,arranging in order and densely,regularly directing,branching in twice with curved top.The histological observation found that dung beetle’s setae are empty inside with lots micro-foramens communicating to the inner side on the base of the buds and sticks on the seta and also connecting with the oil glands below the integument,but without the erect muscle. Gecko setae are surrounded by fat cells and muscles.Results from functional experiments suggest that deformation of the setae of the bung beetle integument could reduce the anti-adherent function and also the same kind of change could reduce the adherent function of the gecko setae on the leg bottom.These results offer important information for preparation of the soil machine and components imitating dung beetle setae flexible non-adherence and for designing artificial setae imitating the gecko’s adherent setae.展开更多
Cow milk is most widely consumed; however,non-cattle milk has gained increasing interest because of added nutritive values. We compared the health effects of yak,cow,and camel milk in rats. By measuring several plasma...Cow milk is most widely consumed; however,non-cattle milk has gained increasing interest because of added nutritive values. We compared the health effects of yak,cow,and camel milk in rats. By measuring several plasma immune factors,significantly more interferon-c was detected in the camel than the yak(P = 0.0020) or cow(P = 0.0062) milk group. Significantly more Ig M was detected in the yak milk than the control group(P = 0.0071). The control group had significantly less interleukin 6 than the yak(P = 0.0499)and cow(P = 0.0248) milk groups. The fecal microbiota of the 144 samples comprised mainly of the Firmicutes(76.70 ± 11.03%),Bacteroidetes(15.27 ± 7.79%),Proteobacteria(3.61 ± 4.34%),and Tenericutes(2.61 ± 2.53%) phyla. Multivariate analyses revealed a mild shift in the fecal microbiota along the milk treatment. We further identified the differential microbes across the four groups. At day 14,22 and 28 differential genera and species were identified(P = 0.0000–0.0462),while 8 and 11 differential genera and species(P = 0.0000–0.0013) were found at day 28. Some short-chain fatty acid and succinate producers increased,while certain health-concerned bacteria(Prevotella copri,Phascolarctobacterium faecium,and Bacteroides uniformis) decreased after 14 days of yak or camel milk treatment. We demonstrated that different animal milk could confer distinctive nutritive value to the host.展开更多
基金supported by grants from the National Key R&D Program of China(2022YFA1305600)National Natural Science Foundation of China(82100950,82470602,and 82470600)Natural Science Foundation of Shanghai(23ZR1452600)。
文摘Background:Recent studies suggest an association between the expansion of Prevotella copri and the disease severity in children with metabolic dysfunction-associated steatotic liver disease(MASLD).We aimed to investigate the causative role and molecular mechanisms of P.copri in pediatric MASLD.Methods:C57BL/6 J mice aged 3 weeks were fed a high-fat diet(HFD)and orally administered with P.copri for 5 weeks.We assessed the key features of MASLD and the gut microbiota profile.By untargeted metabolomics on mouse fecal samples and the supernatant from P.copri culture,we identified P.copriderived metabolite and tested its effects in vitro.Results:In HFD-fed mice,administration of P.copri significantly promoted liver steatosis.Genes associated with inflammation and fibrosis were significantly upregulated in the livers from the HFD+P.copri group compared with those in the livers from the HFD group.In addition,P.copri reduced gut microbial diversity,increased the proportion of Firmicutes and decreased Bacteroidota.Importantly,5-aminopentanoic acid(5-AVA)was significantly enriched in both mouse feces from the HFD+P.copri group and the culture supernatant of P.copri.In vitro,5-AVA aggravated palmitic acid-induced lipid accumulation in HepG2 cells and primary mouse hepatocytes.Mechanistically,P.copri-produced 5-AVA exacerbated hepatic steatosis by promoting lipogenesis and fatty acid uptake,while also reducing hepatic very-low-density lipoprotein export.Conclusions:Our findings demonstrated that P.copri promotes liver steatosis in HFD-fed juvenile mice through its metabolite 5-AVA,suggesting its potential as a therapeutic target for the management of pediatric MASLD.
基金supported by the funds fromthe National Natural Science Foundation of China(32102578,U22A20515)National Key R&D Program of China(2023YFD1302300,2023Y FD1301200).
文摘Gut microbiota disruption during the weaning process is a significant factor of intestinal injury.Our previous studies have suggested that Prevotella may play a critical role in causing intestinal inflammation.This study aimed to clarify the impact of Prevotella copri on intestinal injury and the protecting effect by dihydroquercetin (DHQ) in weaned piglets.A total of 108 healthy Duroc×Landrace×Yorkshire weaned piglets,aged 21 d,were randomly allocated into 3 groups with 6 replicates and 6 piglets per replicate.The piglets were the following diets for 28 d:1) a basal diet,2) basal diet containing1.0×10^(8)CFU/kg P.copri,3) basal diet supplemented with 1.0×10^(8)CFU/kg P.copri and 100 mg/kg DHQ.Results showed that P.copri decreased significantly the average daily gain (ADG)(P<0.001),which was recovered by supplementation of DHQ with decreased serum levels of malondialdehyde (MDA),interleukin (IL)-2 and IL-8 but increased total superoxide dismutase (T-SOD) activity and IL-10 in weaned piglets (P<0.001).Moreover,DHQ increased the expression of tight junction proteins (claudin-2,occludin and tight junction protein zonula occludens protein-1 (ZO-1) and the mRNA expression of glutathione peroxidase 4 (GPX-4) in ileum (P<0.001).Intestinal flora analysis showed that P.copri increased the relative abundance of Prevotella (P=0.026) and Eubacterium coprostanoligenes group(P<0.001),but decreased the relative abundance of Lachnospiraceae NK4A136 group (P<0.001),while supplementation of DHQ reduced the relative abundance of Prevotella (P=0.026).Metabolomics results indicated that P.copri enhanced the content of 12-OH bile acid,but decreased the contents of glycodeoxycholic acid (GDCA) and glycochenodeoxycholic acid (GCDCA)(P<0.001),while DHQ reduced the12-OH bile acid content (P<0.001) and increased the GDCA content (P=0.020).In summary,P.copri caused intestinal injury and reduced growth performance in weaned piglets,and DHQ showed a protective effect by modulating gut microbiota and bile acids metabolism.
基金supported by the National Natural Science Foundation of China (81788101,82230060,81630064,and 81701624)the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-017,2021-I2M-1-047,2021-I2M-1-040,and 2021-I2M-1-016)+1 种基金the Capital’s Funds for Health Improvement and Research (2020-2-4019)the National Key Research and Development Program of China (Grant no.2018YFE0207300).
文摘Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P.copri RA,from the feces of RA patients and showed that colonization of P.copri RA exacerbated arthritis in a collagen-induced arthritis(CIA)model.With the presence of P.copri RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation.Colonization of P.copri together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty acids.Succinate promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA model.Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.
基金supported by the National Natural Science Foundation of China(Grant Nos.31670492 and 31500100).
文摘Prevotella copri and its related taxa are widely detected in mammalian gut microbiomes and have been linked with an enterotype in humans.However,their microevolution and macroevolution among hosts are poorly characterized.In this study,extensively collected marker genes and genomes were analyzed to trace their evolutionary history,host specificity,and biogeographic distribution.Investigations based on marker genes and genomes suggest that a P.copri-containing lineage(PCL)harbors diverse species in higher primates.Firstly,P.copri in the human gut consisted of multiple groups exhibiting high genomic divergence and conspicuous but non-strict biogeographic patterns.Most African strains with high genomic divergence from other strains were phylogenetically located at the root of the species,indicating the co-evolutionary history of P.copri and Homo sapiens.Secondly,although long-term co-evolution between PCL and higher primates was revealed,sporadic signals of co-speciation and extensive host jumping of PCL members were suggested among higher primates.Metagenomic and phylogenetic analyses indicated that P.copri and other PCL species found in domesticated mammals had been recently transmitted from humans.Thirdly,strong evidence was found on the extensively horizontal transfer of genes(e.g.,genes encoding carbohydrate-active enzymes)among sympatric P.copri groups and PCL species in the same primate host.Our study provides panoramic insights into the combined effects of vertical and horizontal transmission,as well as potential niche adaptation,on the microevolutionary and macroevolutionary history for an enterotyperepresentative lineage.
文摘Scanning electron microscopy(SEM)and histological techniques were used to observe and study the structure of setae on the integument surface of the dung beetle Copris ochus Motschulsky and on the foot pad of the gecko Gekko gecko and their relationship to anti-adherent and adherent functions respectively.There are very distinctive comparison between the structures and the constructs of the setae on the dung beetle and the gecko:the setae of the dung beetle are ramification of the integument,mainly distributing on the body abdomen surface and the lateral side of the legs,loosely arranging,having different length with many buds and sticks along the whole seta body but without side branches,uprightly directing to the contacting dung face.The setae of the gecko are protuberances from the skin,arranging in order and densely,regularly directing,branching in twice with curved top.The histological observation found that dung beetle’s setae are empty inside with lots micro-foramens communicating to the inner side on the base of the buds and sticks on the seta and also connecting with the oil glands below the integument,but without the erect muscle. Gecko setae are surrounded by fat cells and muscles.Results from functional experiments suggest that deformation of the setae of the bung beetle integument could reduce the anti-adherent function and also the same kind of change could reduce the adherent function of the gecko setae on the leg bottom.These results offer important information for preparation of the soil machine and components imitating dung beetle setae flexible non-adherence and for designing artificial setae imitating the gecko’s adherent setae.
基金The National Natural Science Foundation of China (31460389)the Key Laboratory Major Open Project Fund of Inner Mongolia (20130902) supported this work
文摘Cow milk is most widely consumed; however,non-cattle milk has gained increasing interest because of added nutritive values. We compared the health effects of yak,cow,and camel milk in rats. By measuring several plasma immune factors,significantly more interferon-c was detected in the camel than the yak(P = 0.0020) or cow(P = 0.0062) milk group. Significantly more Ig M was detected in the yak milk than the control group(P = 0.0071). The control group had significantly less interleukin 6 than the yak(P = 0.0499)and cow(P = 0.0248) milk groups. The fecal microbiota of the 144 samples comprised mainly of the Firmicutes(76.70 ± 11.03%),Bacteroidetes(15.27 ± 7.79%),Proteobacteria(3.61 ± 4.34%),and Tenericutes(2.61 ± 2.53%) phyla. Multivariate analyses revealed a mild shift in the fecal microbiota along the milk treatment. We further identified the differential microbes across the four groups. At day 14,22 and 28 differential genera and species were identified(P = 0.0000–0.0462),while 8 and 11 differential genera and species(P = 0.0000–0.0013) were found at day 28. Some short-chain fatty acid and succinate producers increased,while certain health-concerned bacteria(Prevotella copri,Phascolarctobacterium faecium,and Bacteroides uniformis) decreased after 14 days of yak or camel milk treatment. We demonstrated that different animal milk could confer distinctive nutritive value to the host.
