Anatomy promotes neutral coexistence of strains in the human skin microbiome

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(2), P. 171 - 182.e7

Published: Jan. 6, 2022

What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence Cutibacterium acnes, most abundant on human skin. We reconstruct on-person evolution and migration using whole-genome sequencing C. acnes colonies acquired from healthy subjects, including individual skin pores, find considerable spatial structure at level pores. Although lineages (sets separated by <100 mutations) with vitro fitness differences within centimeter-scale regions, each pore is dominated single lineage. Moreover, typically have identical genomes. An absence adaptive signatures suggests genotype-independent source low within-pore diversity. therefore propose that imposes random single-cell bottlenecks; resulting population fragmentation reduces competition promotes coexistence. Our findings suggest therapeutic interventions involving pore-dwelling might focus removing resident populations over optimizing probiotic fitness.

Language: Английский

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Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels

Cell, Journal Year: 2022, Volume and Issue: 185(22), P. 4099 - 4116.e13

Published: Oct. 1, 2022

Some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. We tested mosquito attraction human skin odor and identified who exceptionally or unattractive mosquitoes. These differences were stable over several years. Chemical analysis revealed that highly produce significantly carboxylic acids in their emanations. Mutant lacking chemosensory co-receptors Ir8a, Ir25a, Ir76b severely impaired scent, retained ability differentiate weakly people. The link between elevated "mosquito-magnet" phenotypes genetic mutations acid receptors suggests such compounds contribute differential attraction. Understanding why some humans others provides insights into what odorants most important could inform development effective repellents.

Language: Английский

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The Skin Microbiome: Current Landscape and Future Opportunities

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3950 - 3950

Published: Feb. 16, 2023

Our skin is the largest organ of body, serving as an important barrier against harsh extrinsic environment. Alongside preventing desiccation, chemical damage and hypothermia, this protects body from invading pathogens through a sophisticated innate immune response co-adapted consortium commensal microorganisms, collectively termed microbiota. These microorganisms inhabit distinct biogeographical regions dictated by physiology. Thus, it follows that perturbations to normal homeostasis, occurs with ageing, diabetes disease, can cause microbial dysbiosis increase infection risk. In review, we discuss emerging concepts in microbiome research, highlighting pertinent links between cutaneous repair. Moreover, address gaps current knowledge highlight key areas requiring further exploration. Future advances field could revolutionise way treat associated ageing other pathologies.

Language: Английский

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The Skin Microbiome: Current Techniques, Challenges, and Future Directions

Microorganisms, Journal Year: 2023, Volume and Issue: 11(5), P. 1222 - 1222

Published: May 6, 2023

Skin acts as a barrier that promotes the colonization of bacteria, fungi, archaea, and viruses whose membership function may differ depending on various specialized niches or micro-environments skin. The group microorganisms inhabiting skin, also known skin microbiome, offers protection against pathogens while actively interacting with host's immune system. Some members microbiome can act opportunistic pathogens. is influenced by factors such site, birth mode, genetics, environment, products, conditions. association(s) health disease has (have) been identified characterized via culture-dependent culture-independent methods. Culture-independent methods (such high-throughput sequencing), in particular, have expanded our understanding microbiome's role maintaining promoting disease. However, intrinsic challenges associated low microbial biomass high host content samples hindered advancements field. In addition, limitations current collection extraction biases derived from sample preparation analysis significantly results conclusions many studies. Therefore, present review discusses technical processing samples, advantages disadvantages sequencing approaches, potential future areas focus for

Language: Английский

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Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC

Microbial Genomics, Journal Year: 2023, Volume and Issue: 9(4)

Published: April 28, 2023

Bacterial secondary metabolites, synthesized by enzymes encoded in biosynthetic gene clusters (BGCs), can underlie microbiome homeostasis and serve as commercialized products, which have historically been mined from a select group of taxa. While evolutionary approaches proven beneficial for prioritizing BGCs experimental characterization efforts to uncover new natural dedicated bioinformatics tools designed comparative analysis within focal taxa are limited. We thus developed l ineage s pecific nalysis ( lsa BGC; https://github.com/Kalan-Lab/lsaBGC ) aid exploration microdiversity trends across homologous groupings BGCs, cluster families (GCFs), any bacterial interest. BGC enables rapid direct identification GCFs genomes, calculates statistics conservation genes, builds framework allow base resolution mining novel variants through metagenomic exploration. Through application the suite four genera commonly found skin microbiomes, we insights into evolution diversity their BGCs. show that virulence-associated carotenoid staphyloxanthin Staphylococcus aureus is ubiquitous genus . one GCF encoding biosynthesis showcases evidence plasmid-mediated horizontal transfer (HGT) between species, another appears be transmitted vertically amongst sub-clade skin-associated Further, latter GCF, well conserved S. , has lost most epidermidis common species on human also regarded commensal. identify thousands single-nucleotide (SNVs) Corynebacterium tuberculostearicum sp. complex, narrow, multi-species clade features prevalent healthy microbiomes. Although SNVs were approximately 10 times likely correspond synonymous changes when located top five percentile sites, identified defied this trend predicted amino acid functionally key enzymatic domains. Ultimately, beyond supporting investigations provides important functionalities discovery or directed modification products.

Language: Английский

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Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus

Nature Microbiology, Journal Year: 2023, Volume and Issue: 9(1), P. 200 - 213

Published: Dec. 18, 2023

Language: Английский

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The Central Roles of Keratinocytes in Coordinating Skin Immunity

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(11), P. 2377 - 2398

Published: Aug. 8, 2024

The function of keratinocytes (KCs) to form a barrier and produce cytokines is well-known, but recent progress has revealed many different roles for KCs in regulation skin immunity. In this review, we provide an update on the current understanding how communicate with microbes, immunocytes, neurons, other cells effective immune barrier. We catalog large list genes metabolites that participate host defense discuss mechanisms crosstalk, addressing simultaneously physical barrier, fibroblasts, control signals. Overall, signals sent received by are exciting group therapeutic targets explore treatment dermatologic disorders.

Language: Английский

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Commensal Skin Bacteria Exacerbate Inflammation and Delay Skin Barrier Repair

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(11), P. 2541 - 2552.e10

Published: April 10, 2024

The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse with the model human commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less known about concurrent damage exposure to microbes, despite growing interest in interventional probiotic therapy. Here, we address this open question by applying bacteria at high dose abraded skin. While depletion via antibiotics delayed repair from damage, probiotic-like application commensals-- including xylosus, three distinct isolates S. epidermidis, all other tested also significantly barrier repair. Increased inflammation was observed within four hours persisted through day four, which point displayed chronic wound-like inflammatory state increased neutrophil infiltration, fibroblast activity, decreased monocyte differentiation. Transcriptomic analysis suggested prolonged upregulation early canonical proliferative pathways inhibited progression These results highlight nuanced role members modulating integrity indicate need for caution their development as probiotics.

Language: Английский

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Skin microbiome and dermatologic disorders

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(3)

Published: Feb. 2, 2025

Human skin acts as a physical barrier to prevent the entry of pathogenic microbes while simultaneously providing home for commensal bacteria and fungi. Microbiome sequencing studies have demonstrated unappreciated diversity selectivity these microbes. Functional impact specific strains tune immune system, sculpt microbial community, provide colonization resistance, promote epidermal integrity. Recent integrated microbiome, immunity, tissue integrity understand their interplay in common disorders such atopic dermatitis. In this Review, we explore microbiome shifts associated with cutaneous an eye toward how can be mined identify new therapeutic opportunities.

Language: Английский

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Absolute quantification of the living skin microbiome overcomes relic-DNA bias and reveals specific patterns across volunteers

Microbiome, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 4, 2025

As the first line of defense against external pathogens, skin and its resident microbiota are responsible for protection eubiosis. Innovations in DNA sequencing have significantly increased our knowledge microbiome. However, current characterizations do not discriminate between from live cells remnant dead organisms (relic DNA), resulting a combined readout all microorganisms that were currently present on rather than actual living population Additionally, most methods lack capability absolute quantification microbial load skin, complicating extrapolation clinically relevant information. Here, we integrated relic-DNA depletion with shotgun metagenomics bacterial determination to quantify cell abundances across different sites. Though discovered up 90% be relic DNA, saw no significant effect this relative taxa determined by sequencing. Relic-DNA prior strengthened underlying patterns microbiomes volunteers reduced intraindividual similarity. We abundance fraction alive several common body sites found taxa-specific differential bacteria regions estimates generated total (live + dead) Our results reveal bias has low biomass samples like skin. The similarity following highlights introduced traditional (total DNA) diversity comparisons samples. divergent levels viability measured sites, along inconsistencies vs sequencing, suggest an important hypothesis certain being susceptible pathogen infection. Overall, study demonstrates characterization microbiome overcomes provide baseline will further improve mechanistic studies infection, disease progression, design therapies Video Abstract.

Language: Английский

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