ABSTRACT
Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/microbiology , Genome-Wide Association Study/methods , Intestines/microbiology , Metagenome/genetics , Metagenomics/methods , Asian People , Butyrates/metabolism , China/ethnology , Cohort Studies , Diabetes Mellitus, Type 2/classification , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Feces/microbiology , Genetic Linkage/genetics , Genetic Markers , High-Throughput Nucleotide Sequencing , Humans , Metabolic Networks and Pathways/genetics , Opportunistic Infections/complications , Opportunistic Infections/microbiology , Reference Standards , Sulfates/metabolismABSTRACT
BACKGROUND: To investigate the associations between Vaginal Pathogenic Community with Bacterial vaginosis, Candida vaginitis, and Trichomonas vaginalis in Chinese women. METHOD: In this experiment, ten BV, nine VVC, eight TV patients, and four non-infected healthy women were recruited. The vaginal samples were collected from the vaginal orifice, the middle of the vagina, and vaginal fornix from every participant and conducted with next-generation sequencing (NGS). The NGS was based upon the analysis of bacterial 16S rRNA genes by using the Illumina Miseq system. RESULTS: No significant difference in microbiome community structures was observed for the three sampling sites from the same subject. Compared with the healthy population, patients with BV and TV showed more diverse symptoms and had a lower amount of Lactobacillus but a higher number of BV-related bacteria like Atopobium, Dialister, Sneathia, Mobiluncus, and Prevotella. On the contrary, the species composition of the VVC group is relatively simple, which has a significantly high abundance of Lactobacillus. Eight genera, including Arcanobacterium, Clostridium, Moryella, Mobiluncus, Shuttleworthia, Dialister, Bulleidia, and Megasphaera, were closely correlated with BV. Among vaginal pathogenic bacteria, Anaerococcus, Lysobacter, Mycoplasma, Peptoniphilus, Sneathia, and Prevotella were more common, with higher copy numbers in the TV group. CONCLUSIONS: The data outlined the overall structure of vaginal communities, indicating that BV and TV were touching related to a sharp increase in the rich taxonomy and diversity of vaginal microbiota. VVC group presented a lower variety, with a significantly high abundance of Lactobacillus.
ABSTRACT
To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; nâ=â44), prediabetes (Pre-DM; nâ=â64), or newly diagnosed T2DM (nâ=â13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.
Subject(s)
Diabetes Mellitus, Type 2/microbiology , Glucose Intolerance/microbiology , Microbiota/genetics , Prediabetic State/microbiology , Analysis of Variance , Bacteroides/genetics , Disease Progression , Gastrointestinal Tract/microbiology , Genes, Bacterial , Glucose Intolerance/pathology , Humans , Middle Aged , Molecular Typing , Phylogeny , Principal Component Analysis , RNA, Ribosomal, 16S/genetics , Verrucomicrobia/geneticsABSTRACT
We studied the ability of lpdA gene knockout Escherichia coli to ferment different sugars in mineral salts medium for the production of pyruvate. The sugars studied were glucose, fructose, xylose and mannose at a concentration of 10 g/L. At the same time, effect of inoculum size on lpdA fermentation with glucose was studied. The strain was able to use all sugars for biomass generation and pyruvate production. The lpdA knockout mutant converted glucose, fructose, xylose and mannose to pyruvate with yields of 0.884 g/g, 0.802 g/g, 0.817 g/g and 0.808 g/L, respectively. The pyruvate accumulation curve coupled with cell growth except for mannose as carbon source. When the inoculation size increased, the rate of glucose consumption, pyruvate accumulation and cell growth increased but lower pyruvate concentration. This study demonstrates that E. coli lpdA mutant has the potential to produce pyruvic acid from xylose and mannose.