Biology subjects

Shanmuganayagam, D.

Publications and source records attributed to Shanmuganayagam, D..

4 recordsLinked to original sources

bioRxiv2025

Establishing an ex vivo porcine skin model to investigate the effects of broad spectrum antiseptic on viable skin microbial communities

Incomplete antiseptic efficacy against potentially pathogenic microbial taxa places some patients at disproportionate risk for developing a surgical site infection. Laboratory models capable of interrogating the effects of antiseptics on the skin and its complex microbial communities are desperately needed to improve and better tailor antiseptic formulations. This work aims to establish an ex vivo porcine skin model to explore the impact of topical antiseptics on complex skin microbial communities and superficial skin lipids. Microbiome samples were treated with propidium-monoazide to selectively evaluate DNA from viable microorganisms. Bacterial abundances were assessed via viability-qPCR and quantitative culture. Viable community populations were evaluated with 16S rRNA gene sequencing. Epidermal biopsies were collected at multiple timepoints for lipidomic assessment via LC/MS. The ex vivo environment promoted shifts in porcine skin lipid composition and microbial communities over the experiments duration. Compared to water treated control skin, skin treated with the antiseptic chlorhexidine gluconate had significantly lower culturable and bioburden determined by viability-qPCR. Compared to water treated skin, viable microbial communities on CHG treated skin displayed greater relative abundance of several gut associated and Gram-negative bacterial taxa, including SMB53, Turicibacter, Pseudomonas and Proteus. Collectively these findings highlight the utility of an ex vivo porcine skin system for interrogating the impacts of antimicrobial disruption to complex microbial ecosystems, and ultimately for the future testing and development of improved antiseptic formulations.

microbiology↗

bioRxiv2024

The Porcine Skin Microbiome Exhibits Broad Fungal Antagonism

The skin and its microbiome function to protect the host from pathogen colonization and environmental stressors. In this study, using the Wisconsin Miniature Swine model, we characterize the porcine skin fungal and bacterial microbiomes, identify bacterial isolates displaying antifungal activity, and use whole-genome sequencing to identify biosynthetic gene clusters encoding for secondary metabolites that may be responsible for the antagonistic effects on fungi. Through this comprehensive approach of paired microbiome sequencing with culturomics, we report the discovery of novel species of Corynebacterium and Rothia. Further, this study represents the first comprehensive evaluation of the porcine skin mycobiome and the evaluation of bacterial-fungal interactions on this surface. Several diverse bacterial isolates exhibit potent antifungal properties against fungal pathogens in vitro. Genomic analysis of inhibitory species revealed a diverse repertoire of uncharacterized biosynthetic gene clusters suggesting a reservoir of novel chemical and biological diversity. Collectively, the porcine skin microbiome represents a potential unique source of novel antifungals. HighlightsO_LIPorcine skin bacterial communities are consistent with previous reports on porcine and human skin. C_LIO_LIFungal community composition resembles mycobiomes from other mammalian skin, but not human skin. C_LIO_LIBacteria isolated from porcine skin have antimicrobial and particularly strong antifungal activity in vitro. C_LIO_LIDiscovered three new Corynebacterium species and one new Rothia species. C_LI

microbiology↗

bioRxiv2022

Dietary Lipid Oxidization Products Alter Growth, Adiposity and Gut Microbial Ecology in Prepubertal Porcine Model

Elevated levels of dietary fats in westernized diets, associated with increased risk of obesity and other chronic diseases, are increasingly consumed by children in the United States. Cooking practices such as high heat frying and increased use of oxidizable sources of fats have introduced high levels of lipid oxidation products (LOPs) into these diets. The effects of these highly reactive dietary compounds on human biology are largely unstudied, especially in the gut where these compounds are likely present at higher concentrations. Given that the gut microbiome can be influenced by dietary components and then in turn have a systemic impact, we investigated the effects of consuming LOPs on gut bacterial and fungal communities and on growth and body composition during the prepubertal period in a porcine model. The presence of LOPs in the high fat diet reduced growth and body fat gain in the model. The gut microbiome was uniquely altered by both high fat and the presence of LOPs, with notable changes in the abundances of Turicibacterales, Spriochaetales, RF39, Lactobacillales and Erysipelotrichales. The mycobiome was dominated by Kazachstania, a porcine specific yeast, which was only minimally influenced by the dietary regimen. Application of machine learning identified dietary fat and LOPs as strong predictors of body fat. The genus Methanobrevibacter was the key microbial predictor of body fat. This study highlights the need for further studies on the biological effects of LOPs which have become ubiquitous in human, livestock and pet diets in developed countries.

physiology↗

bioRxiv2020

Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity

DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age, epigenetic clocks, for many species. Using a custom methylation array, we generated DNA methylation data from n=238 porcine tissues including blood, bladder, frontal cortex, kidney, liver and lung, from domestic pigs (Sus scrofa domesticus) and minipigs (Wisconsin Miniature Swine). We present 4 epigenetic clocks for pigs that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (pig and human). Two dual-species human-pig pan-tissue clocks accurately measure chronological age and relative age, respectively. We also characterized CpGs that differ between minipigs and domestic pigs. Strikingly, several genes implicated by our epigenetic studies of minipig status overlap with genes (ADCY3, TFAP2B, SKOR1, and GPR61) implicated by genetic studies of body mass index in humans. In addition, CpGs with different levels of methylation between the two pig breeds were identified proximal to genes involved in blood LDL levels and cholesterol synthesis, of particular interest given the minipigs increased susceptibility to cardiovascular disease compared to domestic pigs. Thus, inbred differences of domestic and minipigs may potentially help to identify biological mechanisms underlying weight gain and aging-associated diseases. Our porcine clocks are expected to be useful for elucidating the role of epigenetics in aging and obesity, and the testing of anti-aging interventions.

developmental biology↗