Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

Objective To study the protective effect and mechanism of maslinic acid (MA) on acute liver injury (ALI) in rats.Methods Fifty BALB/c mice were randomly divided into control group,model group,and low (12.5 mg/kg),medium (25.0 mg/kg) and high doses (50.0 mg/kg) of MA,with 10 rats in each group.The control group was intraperitoneally injected with normal saline.The other groups were intraperitoneally injected with lipopolysaccharide (LPS) (50 mg/kg) and D-Gal N (500 mg/kg) to prepare mouse AL[model.The MA groups were administered with 12.5,25.0,50.0 mg/kg MA 1 h before model establishment,respectively.All the mice were sacrificed 6 h after model establishment,and serum and liver tissues were collected.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured.Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue.Thiobarbituric acid method was used to determine malondialdehyde (MDA).H2O2 reaction product colorimetric was used to determine the content of myeloperoxidase (MPO).The tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue was detected by enzyme-linked immunosorbent assay,respectively.Western Blot was conducted to detect the expression of nuclear factor E2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1) and the activation of nuclear factor-kappa B (NF-κB) pathway.Results Compared with the model group,the liver histopathology in the low,medium and high doses MA groups was significantly improved.The serum ALT and AST levels were decreased,and the differences were statistically significant (all P＜0.05).The contents of MDA and MPO in liver tissues were decreased,and the differences were statistically significant (all P＜0.05).The protein contents of Nrf2 and HO-1 were increased,the differences were statistically significant (all P＜0.05).The NF-κB pathway was inhibited,and the differences were statistically significant (all P＜0.05).The levels of TNF-α and IL-6 in serum and liver tissues were decreased,and the differences were statistically significant (all P＜0.05).Conclusions MA has a protective effect on LPS/D-Gal N-induced ALI,and its mechanism is related to inhibition of NF-κB pathway and activation of Nrf2/HO-1 pathway.

Objective To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF).Methods A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation.Results Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGDgroup, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non-PGD group [PADP ahead of operation (mmHg, 1 mmHg = 0.133 kPa): 33.7±10.5 vs. 25.3±10.1, mPAP ahead of operation (mmHg): 40.4±14.1 vs. 32.8±11.1, the dosage of red cells suspension after the operation (mL): 700 (300, 1500) vs. 300 (300, 500), the total amount of blood transfusion during and after the operation (mL): 2250 (1850, 4275) vs. 1800 (1550, 2800)], with statistically significant differences (all P < 0.05). There were no significant differences in age, gender, BMI, underlying disease, NT-proBNP before operation, PASP before and after operation, PADP and mPAP after operation, duration of operation, amount of plasma and red cells suspension as well as total amount of blood transfusion during operation, plasma amount and total amount of blood transfusion after operation, amount of plasma and red cells suspension during and after operation, use of ECMO during operation, blood purification treatment after operation, and shock after operation between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that the preoperative PADP was the independent risk factor of grade 3 PGD after lung transplantation [odds ratio (OR) = 1.084, 95% confidence interval (95%CI) = 1.016-1.156,P = 0.015]. It was shown by ROC curve that the area under the ROC curve (AUC) of the PADP before operation for predicting the grade 3 PGD after lung transplantation was 0.728. When the cut-off value was 36 mmHg, the sensitivity was 47.1%, and the specificity was 91.4%.Conclusions Compared with the non-PGD group, the patients with higher preoperative PADP were more common in the PGD group, and the patients in the PGD group were more likely to be characterized by grade 3 PGD after lung transplantation. The preoperative PADP was an effective predictor of grade 3 PGD after lung transplantation.