ORCID Profile
0000-0003-3956-4711
Current Organisations
Baker IDI Heart and Diabetes Institute
,
University of Melbourne
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Publisher: BMJ
Date: 25-09-2015
DOI: 10.1136/GUTJNL-2015-309800
Abstract: To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes. We performed metagenome-wide association studies on faecal s les from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls. Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal s les.
Publisher: MDPI AG
Date: 30-09-2022
Abstract: Weight loss and increased physical activity may promote beneficial modulation of the metabolome, but limited evidence exists about how very low-level weight loss affects the metabolome in previously non-obese active in iduals. Following a weight loss period (21.1 ± 3.1 weeks) leading to substantial fat mass loss of 52% (−7.9 ± 1.5 kg) and low body fat (12.7 ± 4.1%), the liquid chromatography-mass spectrometry-based metabolic signature of 24 previously young, healthy, and normal weight female physique athletes was investigated. We observed uniform increases (FDR 0.05) in bile acids, very-long-chain free fatty acids (FFA), and oxylipins, together with reductions in unsaturated FFAs after weight loss. These widespread changes, especially in the bile acid profile, were most strongly explained (FDR 0.05) by changes in android (visceral) fat mass. The reported changes did not persist, as all of them were reversed after the subsequent voluntary weight regain period (18.4 ± 2.9 weeks) and were unchanged in non-dieting controls (n = 16). Overall, we suggest that the reported changes in FFA, bile acid, and oxylipin profiles reflect metabolic adaptation to very low levels of fat mass after prolonged periods of intense exercise and low-energy availability. However, the effects of the aforementioned metabolome subclass alteration on metabolic homeostasis remain controversial, and more studies are warranted to unravel the complex physiology and potentially associated health implications. In the end, our study reinforced the view that transient weight loss seems to have little to no long-lasting molecular and physiological effects.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2020
DOI: 10.1101/2020.09.12.20193045
Abstract: Co-evolution between humans and the microbial communities colonizing them has resulted in an intimate assembly of thousands of microbial species mutualistically living on and in their body and impacting multiple aspects of host physiology and health. Several studies examining whether human genetic variation can affect gut microbiota suggest a complex combination of environmental and host factors. Here, we leverage a single large-scale population-based cohort of 5,959 genotyped in iduals with matched gut microbial shotgun metagenomes, dietary information and health records up to 16 years post-s ling, to characterize human genetic variations associated with microbial abundances, and predict possible causal links with various diseases using Mendelian randomization (MR). Genome-wide association study (GWAS) identified 583 independent SNP-taxon associations at genome-wide significance ( p .0×10 -8 ), which included notable strong associations with LCT ( p =5.02×10 -35 ), ABO ( p =1.1×10 -12 ), and MED13L ( p =1.84×10 -12 ). A combination of genetics and dietary habits was shown to strongly shape the abundances of certain key bacterial members of the gut microbiota, and explain their genetic association. Genetic effects from the LCT locus on Bifidobacterium and three other associated taxa significantly differed according to dairy intake. Variation in mucin-degrading Faecalicatena lactaris abundances were associated with ABO , highlighting a preferential utilization of secreted A/B/AB-antigens as energy source in the gut, irrespectively of fibre intake. Enterococcus faecalis levels showed a robust association with a variant in MED13L , with putative links to colorectal cancer. Finally, we identified putative causal relationships between gut microbes and complex diseases using MR, with a predicted effect of Morganella on major depressive disorder that was consistent with observational incident disease analysis. Overall, we present striking ex les of the intricate relationship between humans and their gut microbial communities, and highlight important health implications.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2017
DOI: 10.1038/SREP44935
Abstract: The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in in iduals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori , we observed other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although s les were largely converged according to the relative abundance of HP, a clear separation of GC and other s les was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial ersity, this association was weak in GC s les which tended to have lower bacterial ersity compared with other s les with similar HP levels. Eradication of HP resulted in an increase in bacterial ersity and restoration of the relative abundance of other bacteria to levels similar to in iduals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial ersity, which could be restored by antibiotic treatment.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2012
DOI: 10.1038/NATURE11450
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 in iduals. 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 in iduals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 24-12-2014
DOI: 10.1038/TPJ.2013.42
Abstract: Bariatric surgery is a well-established approach to improve metabolic disease in morbidly obese patients with high cardiovascular risk. The post-operative normalization of lipid metabolism has a central role in the prevention of future cardiovascular events. The aim of the present study therefore was to characterize changes of plasma lipidomic patterns, consisting of 229 lipid species of 13 lipid classes, 3 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients with and without diabetes. RYGB resulted in a 15-32% decrease of body mass index, which was associated with a significant reduction of total cholesterol (TC, -28.3% P=0.02), LDL-cholesterol (LDL-C, -26.8% P=0.03) and triglycerides (TGs, -63.0% P=0.05) measured by routine clinical chemistry. HDL-cholesterol remained unchanged. The effect of RYGB on the plasma lipidomic profile was characterized by significant decreases of 87 lipid species from triacylglycerides (TAGs), cholesterol esters (CholEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), phosphatidylethanolamine ethers (PEOs), phosphatidylinositols (PIs) and ceramides (Cers). The total of plasma lipid components exhibited a substantial decline of 32.6% and 66 lipid species showed a decrease by over 50%. A direct correlation with HbA1C values could be demonstrated for 24 in idual lipid species (10 TAG, three CholE, two LPC, one lysophosphatidylcholine ethers (LPCO) (LPC ether), one PC, two phosphatidylcholine ethers (PCO) and five Cer). Notably, two lipid species (TAG 58:5 and PEO 40:5) were inversely correlated with HbA1C. LPCO, as single whole lipid class, was directly related to HbA1C. These data indicate that RYGB-induced modulation of lipidomic profiles provides important information about post-operative metabolic adaptations and might substantially contribute to improvements of glycemic control. These striking changes in the human plasma lipidome may explain acute, weight independent and long-term effects of RYGB on the cardiovascular system, mental status and immune regulation.
Publisher: Springer Science and Business Media LLC
Date: 02-10-2013
DOI: 10.1038/TPJ.2012.43
Abstract: Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-in idual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)>40 kg m(-)(2)) with T2D. Subsequently, metagenomic data were correlated with clinical indices. Based on gene relative abundance profile, 1061 species, 729 genera, 44 phyla and 5127 KO (KEGG Orthology) were identified. Despite high ersity, bacteria could mostly be assigned to seven bacterial isions. The overall metagenomic RYGB-induced shift was characterized by a reduction of Firmicutes and Bacteroidetes and an increase of Proteobacteria. Twenty-two microbial species and 11 genera were significantly altered by RYGB. Using principal component analysis, highly correlated species were assembled into two common components. Component 1 consisted of species that were mainly associated with BMI and C-reactive protein. This component was characterized by increased numbers of Proteobacterium Enterobacter cancerogenus and decreased Firmicutes Faecalibacterium prausnitzii and Coprococcus comes. Functional analysis of carbohydrate metabolism by KO revealed significant effects in 13 KOs assigned to phosphotransferase system. Spearmen's Rank correlation indicated an association of 10 species with plasma total- or low-density lipoprotein cholesterol, and 5 species with triglycerides. F. prausnitzii was directly correlated to fasting blood glucose. This is the first clinical demonstration of a profound and specific intra-in idual modification of gut microbial composition by full metagenomic sequencing. A clear correlation exists of microbiome composition and gene function with an improvement in metabolic and inflammatory parameters. This will allow to develop new diagnostic and therapeutic strategies based on metagenomic sequencing of the human gut microbiome.
Publisher: Springer Science and Business Media LLC
Date: 02-2022
DOI: 10.1038/S41588-021-00991-Z
Abstract: Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped in iduals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.
Publisher: Springer Science and Business Media LLC
Date: 07-12-2021
DOI: 10.1038/S41421-021-00356-0
Abstract: The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 in iduals, for both the tongue dorsum ( n = 2017) and saliva ( n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance ( p 3.16 × 10 −11 ). Four of the five associations were well replicated in an independent cohort of 1439 in iduals: rs1196764 at APPL2 with Prevotella jejuni , Oribacterium uSGB 3339 and Solobacterium uSGB 315 rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215 , Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense rs4911713 near OR11H1 with species F0422 uSGB 392 and rs36186689 at LOC105371703 with Eggerthia . Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between in iduals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each in idual.
No related grants have been discovered for Youwen Qin.