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
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 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.
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.
