Erratum: Differential Analysis of Hypertension-Associated Intestinal Microbiota.

[This corrects the article DOI: 10.7150/ijms.29322.].

Age-stratified comparative analysis of the differences of gut microbiota associated with blood glucose level.

BACKGROUND: Gut bacteria are an important component of the microbiota ecosystem in humans and other animals, and they play important roles in human health. The aim of this study was to investigate the relationship between gut microbiota and multiple demographical-, behavioral-, or biochemical-related factors in subjects with chronic disease. Subjects with a very wide age range who participated in community-based chronic disease prevention and screening programs in China were enrolled. We analyzed the intestinal microbiota composition using 16S rRNA-based high-throughput sequencing of fecal samples, analyzed the association between gut microbiota structure and multiple demographical, behavioral, and biochemical factors, and compared the differences in microbiota composition in age-stratified groups with different blood glucose levels. RESULTS: Our results showed that both age and blood glucose levels had a significant impact on the gut microbiota structure. We also identified several taxa showed distinct abundance in groups with different glucose levels. Lactobacillus and Bifidobacterium at genus level and their related taxa were more abundant in the GLU high group comparing with GLU normal group and in NGR group comparing with DM group. Further analysis using the age-stratified data showed that blood glucose levels had a more significant impact on the gut microbiota in the ≥76 y age group than in the ≤75 y age group, which indicated that it is necessary to take age into account when conducting such studies. Moreover, we identified several taxa that were highly associated with blood glucose levels in the ≥76 y age group but not in the ≤75 y age group. Within the ≥76 y age group, Lachnospiraceae incertae sedis and Bacteroides were more abundant in the GLU normal group, whereas Lactobacillus and Bifidobacterium at genus level were more abundant in the GLU high group. CONCLUSIONS: This result suggested that taxa that are capable of differentiating blood glucose levels might differ significantly in different age groups.

Differential Analysis of Hypertension-Associated Intestinal Microbiota.

Hypertension is the main risk factor for cerebral stroke and death resulting from cerebral stroke. Current association studies on hypertension and intestinal microbiota focus on patients with hypertension (HTN); however, no investigations involving patients with isolated diastolic hypertension (IDH) or systolic hypertension (SH) have been conducted to date. In this study, fecal samples from 62 cases with normal blood pressure (BP) and 67 cases with high BP were used for 16S amplicon sequencing. Sixty-one cases of HTN and 61 corresponding cases with normal BP were obtained by propensity score matching (PSM), and differential analysis was conducted using the DEseq2 package. PSM was also used to match six IDH patients with six controls and to match 35 cases of SH with 35 controls. There were 54 differential genera between the HTN and normal BP groups, and there were five differential genera between the IDH and normal BP groups. There were 38 differential genera between the SH and normal BP groups, including Christensenella. Bayesian network analysis showed that variations in BP influenced microbial abundance. Pearson's correlation analysis showed that bacterial abundance is correlated with BP. Significant differences between the intestinal microbiota of high and normal BP groups were observed. Gut microbiota dysbiosis differed among HTN, IDH, and SH patients. In particular, diastolic blood pressure (DBP) and systolic blood pressure (SBP) were related to different intestinal microbiota.

Measurement of apo(a) kinetics in human subjects using a microfluidic device with tandem mass spectrometry.

RATIONALE: Apolipoprotein(a) [apo(a)] is the defining protein component of lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular disease. The regulation of Lp(a) levels in blood is poorly understood in part due to technical challenges in measuring Lp(a) kinetics. Improvements in the ability to readily and reliably measure the kinetics of apo(a) using a stable isotope labeled tracer is expected to facilitate studies of the role of Lp(a) in cardiovascular disease. Since investigators typically determine the isotopic labeling of protein-bound amino acids following acid-catalyzed hydrolysis of a protein of interest [e.g., apo(a)], studies of protein synthesis require extensive protein purification which limits throughput and often requires large sample volumes. We aimed to develop a rapid and efficient method for studying apo(a) kinetics that is suitable for use in studies involving human subjects. METHODS: Microfluidic device and tandem mass spectrometry were used to quantify the incorporation of [(2)H3]-leucine tracer into protein-derived peptides. RESULTS: We demonstrated that it is feasible to quantify the incorporation of [(2)H3]-leucine tracer into a proteolytic peptide from the non-kringle repeat region of apo(a) in human subjects. Specific attention was directed toward optimizing the multiple reaction monitoring (MRM) transitions, mass spectrometer settings, and chromatography (i.e., critical parameters that affect the sensitivity and reproducibility of isotopic enrichment measurements). The results demonstrated significant advantages with the use of a microfluidic device technology for studying apo(a) kinetics, including enhanced sensitivity relative to conventional micro-flow chromatography, a virtually drift-free elution profile, and a stable and robust electrospray. CONCLUSIONS: The technological advances described herein enabled the implementation of a novel method for studying the kinetics of apo(a) in human subjects infused with [(2)H3]-leucine.