Biology subjects

Ang, Q. Y.

Publications and source records attributed to Ang, Q. Y..

5 recordsLinked to original sources

bioRxiv2025

Large-scale skin metagenomics reveals extensive prevalence, coordination, and functional adaptation of skin microbiome dermotypes across body sites

While skin microbiome studies have increasingly highlighted its importance in health and disease, our understanding of inter-individual heterogeneity in structure and function remains limited, impacting the ability to develop microbiome-based stratification and therapeutics. Powered by comprehensive skin microbiome characterization in a multi-ethnic population-based cohort (>3,550 shotgun metagenomes across 18 sampling sites), we established significant undescribed inter-individual heterogeneity and the extensive prevalence of distinct microbial configurations (17 species-resolution dermotypes) in seven out of nine body sites. Combining functional in silico and in vitro studies revealed insights into how these dermotypes assemble as a function of niche-dependent microbial interactions (e.g. hypoxia-dependent inhibition of S. hominis by S. epidermidis/M. luteus) and metabolic resource utilization (e.g. differential galactose and histidine metabolism). Integration of demographic, skin physiological, and behavioral data further identified >30 significant associations with host attributes. Cross-site analysis revealed remarkable coordination across disparate skin regions (predictive AUC-ROC>0.8) and bilateral consistency (Pearson {pi}>0.95), emphasizing the role of specific microbial and host factors in shaping dermotypes. Finally, we provide multiple lines of evidence that dermotype states impact the risk for skin discomfort (e.g. irritation, itch) and diseases (e.g. eczema), that when combined with our highly accurate dermotype classifiers (AUC-ROC>0.98), provide a new paradigm for understanding skin microbiome function and stratifying patients in the context of skin and other diseases.

genomics↗

bioRxiv2023

A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity

Diet can protect from autoimmune disease; however, whether diet acts via the host and/or microbiome remains unclear. Here, we use a ketogenic diet (KD) as a model to dissect these complex interactions. A KD rescued the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in a microbiota-dependent fashion. Dietary supplementation with a single KD-dependent host metabolite ({beta}-hydroxybutyrate, {beta}HB) rescued EAE whereas transgenic mice unable to produce {beta}HB in the intestine developed more severe disease. Transplantation of the {beta}HB-shaped gut microbiota was protective. Lactobacillus sequence variants were associated with decreased T helper 17 (Th17) cell activation in vitro. Finally, we isolated a L. murinus strain that protected from EAE, which was phenocopied by the Lactobacillus metabolite indole lactic acid. Thus, diet alters the immunomodulatory potential of the gut microbiota by shifting host metabolism, emphasizing the utility of taking a more integrative approach to study diet-host-microbiome interactions.

microbiology↗

bioRxiv2020

Differences in the gut microbiomes of distinct ethnicities within the same geographic area are linked to host metabolic health

BackgroundThe human gut microbiota exhibits marked variation around the world, which has been attributed to dietary intake and other environmental factors. However, the degree to which ethnicity-associated differences in gut microbial community structure and function are maintained following immigration or in the context of metabolic disease is poorly understood. ResultsWe conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area. 16S rRNA gene sequencing revealed significant differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian participants had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White groups could not be explained by reported dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice confirmed that the differences in the gut microbiota of the East Asian and White individuals we analyzed are independent of diet and that they differentially impact host body weight and adiposity in genetically identical mouse recipients. ConclusionsThe reported findings emphasize the utility of studying diverse ethnic groups within a defined geographical location and provide a starting point for dissecting the mechanisms contributing to the complex interactions between the gut microbiome and ethnicity-associated lifestyle, demographic, metabolic, and genetic factors.

microbiology↗

bioRxiv2019

A diet-dependent enzyme from the human gut microbiome promotes Th17 accumulation and colitis

Aberrant activation of Th17 cells by the gut microbiota contributes to autoimmunity; however, the mechanisms responsible and their diet-dependence remain unclear. Here, we show that the autoimmune disease-associated gut Actinobacterium Eggerthella lenta increases intestinal Th17 cells and worsens colitis in a Rorc-dependent and strain-variable manner. A single genomic locus predicted Th17 accumulation. A gene within this locus, encoding the Cgr2 enzyme, was sufficient to increase Th17 cells. Levels of cgr2 were increased in stool from patients with rheumatoid arthritis compared to healthy controls. Dietary arginine blocked E. lenta-induced Th17 cells and colitis. These results expand the mechanisms through which bacteria shape mucosal immunity and demonstrate the feasibility of dissecting the complex interactions between diet, the gut microbiota, and autoimmune disease. One Sentence SummaryAn autoimmune disease-associated bacterium triggers disease due to a diet-dependent enzyme that regulates mucosal immunity.

immunology↗

bioRxiv2018

The Genetic Basis for the Cooperative Bioactivation of Plant Lignans by a Human Gut Bacterial Consortium

Plant-derived lignans, consumed daily by most individuals, are inversely associated with breast cancer; however, their bioactivity is only exerted following gut bacterial conversion to enterolignans. Here, we dissect a four-species bacterial consortium sufficient for all four chemical reactions in this pathway. Comparative genomics and heterologous expression experiments identified the first enzyme in the pathway. Transcriptional profiling (RNAseq) independently identified the same gene and linked a single genomic locus to each of the remaining biotransformations. Remarkably, we detected the complete bacterial lignan metabolism pathway in the majority of human gut microbiomes. Together, these results are an important step towards a molecular genetic understanding of the gut bacterial bioactivation of lignans and other plant secondary metabolites to downstream metabolites relevant to human disease.\n\nOne Sentence SummaryBess et al. provide a first step towards elucidating the molecular genetic basis for the cooperative gut bacterial bioactivation of plant lignans, consumed daily by most individuals, to phytoestrogenic enterolignans.

microbiology↗