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PubMed2026

Human skin microbiota and postpartum depression: A bidirectional Mendelian randomization study.

Postpartum depression (PPD) is a common mental health disorder after childbirth. Although microbiome research in PPD has mainly focused on the gut, the role of skin microbiota remains unclear. We used Mendelian randomization (MR) to assess potential causal associations between skin microbiota and PPD. A bidirectional 2-sample MR analysis used genome-wide association study (GWAS) summary statistics. Genetic instruments for skin microbial features were obtained from a published skin microbiota GWAS, and PPD data were derived from 67,205 mothers (7604 cases, 59,601 controls). Instruments were selected at P <1 × 10-5, linkage disequilibrium-clumped, harmonized, and filtered for weak instruments (F statistic <10). Because this microbiome threshold is exploratory, Benjamini-Hochberg false discovery rate correction was applied within taxonomic levels. The inverse-variance weighted method was primary, complemented by weighted median and mode-based methods. Heterogeneity, pleiotropy, and outliers were assessed using Cochran Q, MR-Egger intercept, and MR-PRESSO. Three skin microbial taxa showed nominal associations with PPD. Higher genetically predicted Acinetobacter on the dorsal forearm (dry skin; 9 single nucleotide polymorphisms [SNPs]; mean F = 22.12) and Proteobacteria in the antecubital fossa (moist skin; 6 SNPs; mean F = 23.44) were associated with increased PPD risk, whereas Betaproteobacteria in the antecubital fossa (11 SNPs; mean F = 21.54) was associated with decreased risk. Associations were directionally consistent, with no substantial heterogeneity or horizontal pleiotropy. After multiple-testing assessment, the findings were exploratory rather than definitive. Reverse MR did not support an effect of PPD on the identified skin microbiota. This MR study provides exploratory genetic evidence linking specific skin microbial features to PPD risk. The findings extend microbiota-related hypotheses beyond the gut microbiome but require validation in larger microbiome GWAS datasets, longitudinal cohorts, and mechanistic studies before clinical or causal conclusions are drawn.

Humans↗

PubMed2026

Immunological, Inflammatory, and Microbiota Determinants of Carpal Tunnel Syndrome: Evidence from Mendelian Randomization.

INTRODUCTION: Carpal Tunnel Syndrome (CTS) is a common peripheral neuropathy, and immune dysregulation and microbial dysbiosis are believed to play a role in its development. However, the cause-and-effect relationships have yet to be clarified. METHODS: Using publicly available Genome-Wide Association Study (GWAS), there are 731 immune cell phenotypes, 91 inflammatory proteins, 150 skin microbiota taxon, and 473 gut microbiota taxon based on two-sample Mendelian Randomization (MR) analysis to test whether there is a causal relationship between them and CTS. The results from the study were shown to have some degree of stability as demonstrated by various sensitivity analyses, which included running heterogeneity tests, performing MR -PRESSO, and running MR-Egger regressions. On the other hand, reverse MR was performed to verify the direction of the association. In addition, a two-step MR mediation analysis was conducted to explore whether there was a mediation effect of gut microbiota and skin microbiota, respectively, of immune and inflammatory traits on CTS. RESULTS: 22 Immune cell traits, 4 Inflammatory proteins, 18 gut microbiota taxa, and 3 skin microbiota taxa are causally associated with CTS. Reverse MR suggested feedback effects of CTS on select immune traits and gut microbiota. Mediation analysis revealed 4 gut microbiota taxa that substantially mediated immune/inflammatory effects upon CTS, with mediation rates as high as 44%; however, skin microbiota did not demonstrate any mediation. DISCUSSION: The immune dysregulation, inflammation, and the gut microbiota that cause CTS are all revealed through this research. Mendelian randomization analysis suggests that traits and inflammatory proteins of immune cells directly increase the risk of CTS, and certain types of gut microbes partially mediate these effects. Therefore, the results show a central role of the immune-gut axis in CTS pathogenesis, and suggest a systemic, rather than a local, immune-microbial interaction in disease development. CONCLUSION: We provided the first causal evidence that immune cells, inflammatory proteins, and CTS risk are causally associated with some specific taxa of gut microbiota. This contributes to a better understanding of the immune-microbiome interactions in the process of occurrence and development of CTS, and also provides theoretical support for precision prevention and treatment.

Humans↗

PubMed2026

Complementary activity of an ancient combination of natural ingredients on the dysbiosis symptoms linked to acne.

ETHNOPHARMACOLOGICAL RELEVANCE: Acne is one of the most common dermatologic diseases in the world. It is due to the secretion of a high level of sebum that causes follicular hyperkeratinisation, alterations of the cutaneous microbiota, and inflammatory processes. One of the first-line treatments is still an antibiotic prescription, that inhibits bacterial growth and, as a consequence, lowers some of the other symptoms. Nevertheless, this high level of antibiotic prescription contributes to the increase of antibiotic resistance. Alternatives to antibiotics are thus highly required, as acne does not represent per se an infection. AIM OF THE STUDY: In the frame of the IRGAP (Interdisciplinary Research Group on Ancient Pharmacopeias) consortium, different preparations dedicated to cutaneous ailments have been identified based on ancient traditional uses, dating back to Antiquity or Middle Ages. Among them, the combination of Aloe vera and Myrrh was widely conserved over centuries. Even though this combination is no longer in use, we wondered why this combination was so widely conserved. We considered the use of this combination of ingredients to treat acne, a case study for which both plants are still used, but separately. MATERIALS AND METHODS: The effects of both plant extracts were analyzed on the growth of different bacteria from the skin microbiota, cultivated alone or in co-culture conditions. As the skin is a rather heterologous environment, we further tested the robustness of our study by varying the experimental conditions. We further analyzed any complementary effects of these extracts on the inflammation process linked to acne. RESULTS: We showed that both plant extracts have complementary effects on micro-organisms and on macrophages. Indeed, while Myrrh extracts inhibited the growth of specific skin microbiota bacteria, Aloe vera gel extracts on the opposite, favored the growth of others: the two plants could act in a complementary way to restore a healthy microbiota. Another complementarity was also observed on macrophages: while Myrrh extracts showed an anti-inflammatory effect, Aloe vera gel extracts showed an antioxidant effect. CONCLUSION: Our results highlight the potential of the combination of Myrrh and Aloe vera to address both the dysbiosis of the skin microbiota and the inflammation associated with acne. Thus, this exploration of forgotten combinations from historical pharmacopoeias underscores the importance of revisiting past traditional knowledge as a source of innovation.

Aloe vera↗

PubMed2026

Antimicrobial resistance in Staphylococcus spp. isolated from sporotrichosis-affected cats in Brazil: Detection of MRSP and MRSA.

Recently, Brazil has experienced a zoonotic emergence of sporotrichosis. The associated cutaneous lesions are often extensive and slow to heal, thereby providing a gateway for opportunistic bacteria belonging to the normal skin microbiota. Among these, Staphylococcus spp. are of particular concern due to their high prevalence and notable levels of antimicrobial resistance. The objective of this study was to identify and characterize Staphylococcus spp. isolated from the cutaneous wounds of domestic cats undergoing treatment for sporotrichosis and exhibiting clinical signs of secondary bacterial infection. A total of 233 samples from 203 cats were analyzed. Staphylococcus spp. was isolated from 156 samples (67%), with S. aureus (42.3%) and S. felis (25.6%) being the most prevalent. Antimicrobial susceptibility testing revealed high levels of resistance to penicillin (51.9%), erythromycin (28.8%), and clindamycin (19.2%). In contrast, most isolates were susceptible to chloramphenicol (98%), ciprofloxacin (96.7%), and nitrofurantoin (93%). Multidrug-resistant strains were identified in 24% (38/156) of the isolates. Overall, 12 isolates (7.7%) were classified as methicillin-resistant staphylococci, including four methicillin-resistant S. pseudintermedius (MRSP) and one methicillin-resistant S. aureus (MRSA). To investigate the genetic profiles and epidemiological relationships of these isolates, all the MRSP and MRSA strains were subjected to whole-genome sequencing. Among the MRSP isolates, four sequence types (STs) were identified, including ST551, the founder of clonal complex (CC)551, which is commonly associated with infection in dogs. The MRSA isolate belonged to ST1176, a member of CC5, which is a globally prevalent lineage and is frequently associated with nosocomial infections in humans. This study demonstrates that Staphylococcus species, including methicillin-resistant isolates, are frequently present in the wounds of sporotrichosis-infected cats exhibiting clinical signs of secondary bacterial infection. The detection of MRSA and MRSP in a cat highlights an additional public health concern associated with feline sporotrichosis and further reinforces the growing concern regarding antimicrobial resistance in companion animals.

Animals↗

PubMed2026

Causal Relationships Between Oral Microbiota and Inflammatory Skin Diseases.

INTRODUCTION AND AIMS: The oral microbiome has been increasingly linked to systemic inflammation and immune dysregulation, but whether specific oral bacteria causally contribute to inflammatory skin diseases remains unclear due to confounding and reverse causation. This study aimed to assess the causal effects of 43 oral microbiota taxa on the risk of five inflammatory skin diseases using a Mendelian randomization (MR) approach. METHODS: We performed a two-sample MR analysis using genetic instruments for oral microbiota derived from publicly available genome-wide association studies and outcome data from the FinnGen consortium. Causal effects of oral taxa on systemic lupus erythematosus, vitiligo, pemphigus, localized scleroderma, and dermatitis herpetiformis were estimated. The inverse-variance weighted method served as the primary analysis, complemented by sensitivity analyses to evaluate horizontal pleiotropy, heterogeneity, and reverse causality. RESULTS: MR analyses identified several putative causal associations between oral microbiota and inflammatory skin diseases. Genus Granulicatella and an unknown Streptococcus species (ASV0009) showed causal effects on systemic lupus erythematosus. Family Lachnospiraceae_[XIV] and an unknown Rothia species (ASV0016) were associated with vitiligo. Five oral microbiota taxa demonstrated causal associations with pemphigus. Actinomyces species micronuciformis was linked to localized scleroderma. Order Fusobacteriales and an unknown Neisseria species (ASV0004) were associated with dermatitis herpetiformis. No significant heterogeneity or horizontal pleiotropy was detected in sensitivity analyses. CONCLUSION: This MR study provides genetic evidence supporting a causal role of specific oral bacteria in the development of several inflammatory skin diseases, highlighting the oral microbiome as a potential contributor to cutaneous autoimmunity and inflammation. CLINICAL RELEVANCE: Our findings highlight the putative role of the oral microbiome as a plausible candidate for mechanistic and clinical investigations into the prevention or adjunctive management of selected inflammatory skin diseases. However, oral hygiene improvement, targeted antimicrobials, and other microbiota-directed interventions were not directly tested in this MR study and remain hypothetical strategies requiring validation in experimental and clinical studies.

Humans↗

PubMed2025

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

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

Humans↗

PubMed2025

A comprehensive reference catalog of human skin DNA virome reveals novel viral diversity and microenvironmental influences.

UNLABELLED: Human skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. A total of 2,760 skin metagenomes from 6 published skin studies were collected. A skin virome catalog was constructed using standard methods in the viromics field. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. We identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs), uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae, the dry skin area is enriched in Autographiviridae and Inoviridae, and the moist skin is enriched in Herelleviridae. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas, Klebsiella, and Staphylococcus are predicted to be infected by phages from the class Caudoviricetes. This comprehensive skin DNA viral catalog significantly advances our understanding of the virome's role within the skin ecosystem. IMPORTANCE: This study presents a comprehensive reference catalog of the human skin DNA virome, constructed from 2,760 metagenomic datasets collected globally. It identified 20,927 viral sequences, with 90.85% representing previously unknown viruses, greatly expanding our understanding of skin viral diversity. The findings reveal significant differences in viral communities between distinct skin microenvironments (oily, dry, and moist) and highlight close interactions between bacteriophages and their bacterial hosts, suggesting a potential role for the virome in maintaining microbial balance and skin health. This extensive skin viral catalog constitutes a crucial resource for future epidemiological and therapeutic research, potentially facilitating the development of novel phage therapies and diagnostic markers for skin disorders.

Humans↗

PubMed2025

Impact of the maternal microbiome on neonatal immune development.

Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.

Humans↗

PubMed2026

Exploring the ecological drivers of bacteriophage diversity and functional viral potential in the skin of the axolotl Ambystoma altamirani.

Bacteriophages play important roles in shaping microbial community dynamics across diverse environments. In the amphibian skin, most microbiome studies have focused on bacteria and their interactions with the fungus Batrachochytrium dendrobatidis (Bd), leaving other microbial components, including viruses, largely unexplored. Here, we present the first characterization of the viral community in the amphibian skin microbiome, focusing on ecological drivers of bacteriophage diversity and functional potential in the axolotl Ambystoma altamirani. Using public shotgun metagenomes, we found that the viral fraction was dominated by bacteriophages of the class Caudoviricetes. Bacteriophage diversity was significantly associated with local physicochemical parameters at the time of sampling, and showed a strong positive correlation with bacterial diversity, whereas no significant associations were detected with the presence of Bd. In addition, seasonality influenced the composition and properties of bacteria-bacteriophage co-abundance networks. Functional annotation of assembled bacteriophage sequences revealed a diverse functional potential, including putative auxiliary metabolic genes, superinfection exclusion, toxin-antitoxin, and virulence factors. Overall, these findings highlight the ecological relevance of bacteriophages in amphibian skin microbiomes and underscore the need for further studies on their role in the amphibian host's health.

Animals↗

PubMed2025

The Streptococcus pyogenes mannose phosphotransferase system (Man-PTS) influences antimicrobial activity and niche-specific nasopharyngeal infection.

Streptococcus pyogenes is a human-adapted pathogen that can cause multiple diseases, including pharyngitis and skin infections. Although this bacterium produces many virulence factors, how S. pyogenes competes with the host microbiota is not well understood. Here, we detected antimicrobial activity from S. pyogenes MGAS8232 that prevented the growth of Micrococcus luteus. This activity was produced when cells were grown in 5% CO2 in M17 media supplemented with galactose; however, the addition of alternative sugars coupled with genome sequencing experiments revealed that the antimicrobial phenotype was not related to classical bacteriocins. To further determine genes involved in the production of this activity, a transposon mutant library in S. pyogenes MGAS8232 identified the mannose phosphotransferase system (Man-PTS), a major sugar transporter, as important for the antimicrobial phenotype. Loss-of-function transposon mutants linked to the antimicrobial activity were identified to also be involved in alternative sugar utilization, and additionally, the Man-PTS was further identified from an inadvertent secondary mutation in a bacteriocin operon mutant. Sugar utilization in the Man-PTS mutants demonstrated that galactose, mannose, and N-acetylglucosamine utilization was impaired. RNA-seq experiments in high and low glucose concentrations further characterized the Man-PTS as a glucose transporter; however, transcriptional regulators or virulence factors were not affected with the loss of the Man-PTS. Deletion of Man-PTS demonstrated defects in a mouse model of nasopharyngeal infection but not skin infection. This work suggests that the ability of S. pyogenes to utilize alternative sugars presented by glycans may play a role in acute infection and interactions with the endogenous microbial population existing in the nasopharynx.IMPORTANCEStreptococcus pyogenes is responsible for over 500,000 deaths per year primarily due to invasive infections and post-infection sequelae, although the most common manifestations include pharyngitis and impetigo. S. pyogenes can adapt to its environment through alternative sugar metabolism. Here, we identified an antimicrobial phenotype that was not bacteriocin-related but a by-product of alternative sugar metabolism. The mannose phosphotransferase system was involved in the production of the antimicrobial and was also important for S. pyogenes to utilize alternative sugars and establish nasopharyngeal infection but not skin infection. Overall, this study identified potential strategies used by S. pyogenes for interactions with the endogenous microbiota and further elucidated the importance of sugar metabolism in acute upper respiratory tract infection.

Streptococcus pyogenes↗

PubMed2025

Challenges and Opportunities in Analyzing Cancer-Associated Microbiomes.

The study of cancer-associated microbiomes has gained significant attention in recent years, spurred by advances in high-throughput sequencing and metagenomic analysis. Microbiome research holds promise for identifying noninvasive biomarkers and possibly new paradigms for cancer treatment. In this review, we explore the key computational challenges and opportunities in analyzing cancer-associated microbiomes (in tumor/normal tissues and other body sites, e.g., gut, oral, and skin), focusing on sequencing-driven strategies and associated considerations for taxonomic and functional characterization. The discussion covers the strengths and limitations of current analysis tools for identifying contamination, determining compositional bias, and resolving species and strains, as well as the statistical, metabolic, and network inferences that are essential to uncover host-microbiome interactions. Several key considerations are required to guide the choice of databases used for metagenomic analysis in such studies. Recent advances in spatial and single-cell technologies have provided insights into cancer-associated microbiomes, and Artificial Intelligence-driven protein function prediction might enable rapid advances in this field. Finally, we provide a perspective on how the field can evolve to manage the ever-growing size of datasets and generate robust and testable hypotheses. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

Humans↗