Objective： The association between gut microbiota composition and biomarkers of immune activation and inflammation was assessed in the elderly. Patients： Serum inflammation markers of fifty-five outpatients （29 fem...Objective： The association between gut microbiota composition and biomarkers of immune activation and inflammation was assessed in the elderly. Patients： Serum inflammation markers of fifty-five outpatients （29 females, 26 males, aged 78 ＋ 8.5 years） were analyzed. Stool specimens and thus data on gut microbiota were available from a subgroup of 23 individuals （9 females and 14 males）. Results： Global cerebral atrophy was found in all magnet resonance tomography scans. Mean mini-mental-score examination in Alzheimer＇s disease patients was 18.8 ± 7.1, in patients with mild cognitive impairment 27.8 ± 1.5. Serum neopterin concentrations correlated with concentrations of fecal S100A12 （p 〈 0.001） and cq-antitrypsin （p 〈 0.05）. Faecalibacterium prausnitzii correlated with MMSE （p 〈 0.05）, with Akkermansia muciniphila （p 〈 0.01） and with serum neopterin （p 〈 0.05）. Fecal zonulin correlated inversely with Clostridium cluster I （p 〈 0.02）. Conclusions： Our results underline earlier in vitro and animal studies that cognitive decline associates with age-related changes in the intestinal microbiota and neuroinflammation. However, only correlational evidence can be reported, and a causative relationship still has to be demonstrated.展开更多
Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever(FMF).Pyrin can interact with the inflammasome a...Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever(FMF).Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells,but the physiological function of Pyrin has been unknown for many years.Here we summarize previous studies of Pyrin function under the context of FMF and immunity,and discuss a recent study demonstrating that Pyrin forms an inflammasome complex for caspase-1 activation in innate immunity.Pyrin inflammasome detects inactivating modifications of host Rho GTPases by diverse bacterial toxins and infections,including Clostridium difficile glucosylating cytotoxin Tcd B,FIC-domain adenylyltransferase effectors from Vibrio parahaemolyticus and Histophilus somni,ADP-ribosylating Clostridium botulinum C3 toxin as well as Burkholderia cenocepacia infection.The mode of Pyrin action,i.e.,sensing pathogen virulence activity rather than directly recognizing a microbial molecule,represents a new paradigm in innate immunity.展开更多
文摘Objective： The association between gut microbiota composition and biomarkers of immune activation and inflammation was assessed in the elderly. Patients： Serum inflammation markers of fifty-five outpatients （29 females, 26 males, aged 78 ＋ 8.5 years） were analyzed. Stool specimens and thus data on gut microbiota were available from a subgroup of 23 individuals （9 females and 14 males）. Results： Global cerebral atrophy was found in all magnet resonance tomography scans. Mean mini-mental-score examination in Alzheimer＇s disease patients was 18.8 ± 7.1, in patients with mild cognitive impairment 27.8 ± 1.5. Serum neopterin concentrations correlated with concentrations of fecal S100A12 （p 〈 0.001） and cq-antitrypsin （p 〈 0.05）. Faecalibacterium prausnitzii correlated with MMSE （p 〈 0.05）, with Akkermansia muciniphila （p 〈 0.01） and with serum neopterin （p 〈 0.05）. Fecal zonulin correlated inversely with Clostridium cluster I （p 〈 0.02）. Conclusions： Our results underline earlier in vitro and animal studies that cognitive decline associates with age-related changes in the intestinal microbiota and neuroinflammation. However, only correlational evidence can be reported, and a causative relationship still has to be demonstrated.
基金supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institutethe Beijing Scholar Program to Shao Feng+2 种基金Other financial supports include the National Basic Research Program of China(2012CB518700),the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08020202)National Science Fund for Distinguished Young Scholars(31225002)to Shao Feng
文摘Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever(FMF).Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells,but the physiological function of Pyrin has been unknown for many years.Here we summarize previous studies of Pyrin function under the context of FMF and immunity,and discuss a recent study demonstrating that Pyrin forms an inflammasome complex for caspase-1 activation in innate immunity.Pyrin inflammasome detects inactivating modifications of host Rho GTPases by diverse bacterial toxins and infections,including Clostridium difficile glucosylating cytotoxin Tcd B,FIC-domain adenylyltransferase effectors from Vibrio parahaemolyticus and Histophilus somni,ADP-ribosylating Clostridium botulinum C3 toxin as well as Burkholderia cenocepacia infection.The mode of Pyrin action,i.e.,sensing pathogen virulence activity rather than directly recognizing a microbial molecule,represents a new paradigm in innate immunity.
