Search bioRxiv⌕ Search

Biology subjects

Wijaya, I.

Publications and source records attributed to Wijaya, I..

3 recordsLinked to original sources

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↗

Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes

While rapid demographic changes in Asia are driving the incidence of chronic diseases related to aging, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging the availability of a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun metagenomic sequencing to do high-resolution taxonomic and functional characterization of their gut microbiomes (n=234). Joint species-level analysis with other Asian cohorts identified a distinct age-associated shift in Asian gut metagenomes, characterized by a reduction in microbial richness, and enrichment of specific Alistipes and Bacteroides species (e.g. Alistipes shahii and Bacteroides xylanisolvens). Functional pathway analysis confirmed that these changes correspond to a metabolic potential expansion in aging towards alternate pathways that synthesize and utilize amino-acid precursors, relative to the dominant microbial guilds that typically produce butyrate in the gut from pyruvate (e.g. Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust gut microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species such as Parabacteroides goldsteinii and pathobionts such as Klebsiella pneumoniae, highlighting the role of the microbiome as biomarkers and potential intervention targets for promoting healthy aging.

genomics↗

ROS-induced translational regulation--through spatiotemporal differences in codon recognition--is a key driver of brown adipogenesis

The role of translational regulation in brown adipogenesis is relatively unknown. Localized translation of mRNAs encoding mitochondrial components enables swift mitochondrial responses, but whether this occurs during brown adipogenesis, which involves massive mitochondrial biogenesis, has not been explored. Here, we used ribosome profiling and RNA-Seq, coupled with cellular fractionation, to obtain spatiotemporal insights into translational regulation. During brown adipogenesis, a translation bias towards G/C-ending codons is triggered first in the mitochondrial vicinity by reactive oxygen species (ROS), which later spreads to the rest of the cell. This translation bias is induced through ROS modulating the activity of the tRNA modification enzyme, ELP3. Intriguingly, functionally relevant mRNAs, including those encoding ROS scavengers, benefit from this bias; in so doing, ROS-induced translation bias both fuels differentiation and concurrently minimizes oxidative damage. These ROS-induced changes could enable sustained mitochondrial biogenesis during brown adipogenesis, and explain in part, the molecular basis for ROS hormesis.

molecular biology↗