Humans are home to a diverse community of bacteria, many of which form symbiotic relationships with their host. Notably, tumors can also harbor their own unique bacterial populations that can influence tumor growth and progression. These bacteria, which selectively colonize hypoxic and acidic tumor microenvironments, present a novel therapeutic strategy to combat cancer. Advancements in synthetic biology enable us to safely and efficiently program therapeutic drug production in bacteria, further enhancing their potential. This review provides a comprehensive guide to utilizing bacteria for cancer treatment. We discuss key considerations for selecting bacterial strains, emphasizing their colonization efficiency, the delicate balance between safety and anti-tumor efficacy, and the availability of tools for genetic engineering. We also delve into strategies for precise spatiotemporal control of drug delivery to minimize adverse effects and maximize therapeutic impact, exploring recent examples of engineered bacteria designed to combat tumors. Finally, we address the underlying challenges and future prospects of bacterial cancer therapy. This review underscores the versatility of bacterial therapies and outlines strategies to fully harness their potential in the fight against cancer.

Species-level uniformity on the skin surface masks substantial strain-level diversity modulated by ecological dynamics. In this issue of Cell Host & Microbe, Jacob et al. uncover dynamic intraspecies behaviors, revealing different patterns of colonization and persistence for two important skin commensals.

The skin is the primary barrier against environmental insults, safeguarding the body from mechanical, chemical and pathogenic threats. The frequent exposure of the skin to environmental challenges requires an immune response that incorporates a sophisticated combination of defenses. Tissue-resident lymphocytes are pivotal for skin immunity, working in tandem with commensal bacteria to maintain immune surveillance and homeostasis, as well as participating in the pathogenesis of several skin diseases. Indeed, it has been estimated that the human skin harbors nearly twice as many T cells as found in the circulation. Effective treatment of skin diseases and new therapy development require a thorough understanding of the complex interactions among skin tissue, immune cells and the microbiota, which together regulate the skin's immune balance. This Review explores the latest developments and understanding of this critical barrier organ, with a specific focus on the role of skin-resident T cells.

Atopic dermatitis is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of atopic dermatitis involves critical cytokines such as IL-4, IL-17, interferon-γ, and IL-10, which contribute to the imbalance in T helper cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in atopic dermatitis, have been underexplored. This study seeks to alleviate atopic dermatitis symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNCB-induced atopic dermatitis mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the T helper 1 / T helper 2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for atopic dermatitis.

Demodex mites are among the most prevalent human parasites. While commonly found on healthy individuals, an overpopulation of this arachnid resident of human skin triggers demodicosis, a neglected yet widely prevalent disease with considerable skin and eye morbidity. Despite its health impact, demodicosis remains overshadowed by other common skin diseases. This neglect has significant consequences for individual and public health, which require a paradigm shift in our understanding and management of this ubiquitous ectoparasite. We reviewed the literature to re-evaluate the pathogenicity of the Demodex mite, paying particular attention to the primary risk factors-immune dysregulation, altered microbiota, and concurrent infections-that may contribute to pathogenicity. We discuss the challenges in combating neglect of demodicosis and provide updates on various impediments in achieving this goal. We explore the issues and research gaps in various domains such as those related to parasite biology, pathogenesis, diagnosis, treatment, prevention and control. We present potential solutions and outline future prospects for tackling this important disease. Finally, we hope to catalyze greater attention and investment for this neglected public health issue.

Raising awareness of Demodex and demodicosis and its major contribution to human diseases requires a multidisciplinary approach. Efforts to prioritize its place on the global health agenda, invest in research, improve diagnostic tools, and develop new treatment strategies will lead to improved public health outcomes and a higher quality of life for those affected.

Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix (ECM) remodeling, regulating a wide range of cellular and immune processes in both homeostatic and pathological conditions. Host-microbiota interactions play a critical role in maintaining ECM balance; however, during dysbiosis, this regulation is disrupted, leading to compromised barrier integrity, pathogen translocation into circulation, and the development of systemic diseases and cancer. This review highlights the bidirectional relationship between MMP expression/activity and microbiota dysbiosis, emphasizing tissue-specific alterations in MMP activity that contribute to disease progression. In addition, it integrates interdisciplinary evidence to illustrate the MMP-dependent mechanisms underlying various pathologies associated with oral and gut microbiome dysbiosis, including long-range effects through the gut-skin and gut-brain axes. Thus, this review introduces the emerging field of MatrixBiome, which explores the complex interactions between the ECM, microbiota, and host tissues. Finally, it also outlines therapeutic strategies to modulate MMP levels, either indirectly through microbiome-targeted approaches (e.g., prebiotics, probiotics, and postbiotics) or directly using MMP inhibitors, offering promising avenues for future clinical interventions.

Previous observational studies have indicated a correlation between the skin microbiome and Type 2 diabetes (T2DM). It is hypothesized that this causal relationship may be influenced by inflammatory responses. However, these factors as determinants of T2DM remain largely unexplored.

This study incorporated data from the GWAS database on the skin microbiome, 91 types of inflammatory cytokines, and T2DM. We employed two-sample MR and multivariable MR methods to assess the correlation between the skin microbiome and T2DM, and to investigate whether this correlation is affected by inflammatory cytokines.

The results of the two-sample MR analysis indicate that within the skin microbiome, genetically predicted genus: Acinetobacter, class: Alphaproteobacteria, genus: Bacteroides, ASV005[Propionibacterium granulosum], and ASV072[Rothia mucilaginosa] are associated with an increased risk of T2DM, while phylum: Proteobacteria, genus: Enhydrobacter, family: Clostridiales, ASV006[Staphylococcus hominis] serve as protective factors against T2DM. Among the inflammatory cytokines, levels of Macrophage colony-stimulating factor 1, Tumor necrosis factor receptor superfamily member 9, Urokinase-type plasminogen activator, and C-C motif chemokine 28 are associated with an increased risk of T2DM. Multivariable MR analysis further revealed that Macrophage colony-stimulating factor 1 levels act as a mediating factor between ASV072[Rothia mucilaginosa] and T2DM.

In this study, we found a connection between the skin microbiome and T2DM, with inflammatory cytokines playing a key role in this relationship. This research helps us better understand this complex link and shows that addressing inflammation is important for preventing and treating diabetes. This could greatly benefit public health by reducing the impact of diabetes and its complications. Our results suggest that future studies should explore the specific biological interactions between the skin microbiome and diabetes to develop more effective risk management and treatment strategies from a microbial perspective.

The early life period is increasingly being recognized as a window of opportunity to shape immunity, where microbiota and related probiotics have an important impact. Innate γδ T cells are the first T cells generated in utero, populating epithelial tissues such as the lung and contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate γδ T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth, the murine lung T cell population was specifically dominated by IL17-committed γδ T cells expressing an invariant Vγ6Vδ1 TCR. Single-cell RNA-sequencing showed that the biased IL17-commitment of perinatal lung γδT cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung Vγ6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus (L.rhm.), but not of Bifidobacterium animalis subsp. lactis (B.lac.), increased significantly their frequency, resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed γδT cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process.

Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and stratum corneum (SC) have significantly enhanced our knowledge of skin barrier functions. TJs, located in the granular layer of the epidermis, are crucial boundary elements in the differentiation process, particularly in the transition from living cells to dead cells. The SC forms from dead keratinocytes via corneoptosis and features three distinct pH zones critical for barrier function and homeostasis. Additionally, the SC-skin microbiota interactions are crucial for modulating immune responses and protecting against pathogens. In this review, we explore how these components contribute both to healthy and disease states. By targeting the skin barrier in therapeutic strategies, we can enhance its integrity, modulate immune responses, and ultimately improve outcomes for patients with inflammatory skin conditions.

Prurigo nodularis (PN) is a chronic skin condition that profoundly impacts quality of life. Histopathological studies of itchy hyperkeratotic nodules show dense infiltrates of T lymphocytes, mast cells, and eosinophils. A robust inflammatory response is implicated, coupled with key changes in neuronal plasticity that affect nerve fiber architecture and function. The microbial community in PN lesions exhibits a distinct composition, marked by decreased α-diversity and a prominent increase in Staphylococcus aureus (S aureus). This alteration appears to contribute to the disease's pathophysiology, causing further disruption of the skin barrier, immune dysregulation, and neuronal plasticity. There is ample evidence that virulence factors of S aureus promote Th2, Th17, and Th22 cytokine production, which are key to PN. In addition, S aureus V8 protease (Endoproteinase Glu-C) has recently been identified to trigger robust itch by activating protease-activated receptor 1 (PAR1) on sensory neurons. This review underscores the complex interplay between the altered microbiome and the itch-scratch cycle of PN, providing insights into potential therapeutics targeting the skin microbiome. A multidisciplinary approach is crucial for providing relief to individuals suffering from this skin condition.

Metal-based nanoenzymes with excellent biocompatibility and stable chemical properties are an effective antimicrobial agent against bacterial resistance due to their radical-mediated catalysis. In this work, due to the pH of most bacterial infection sites being close to neutral, targeting the problem of Fe3O4@Ag difficulty in maintaining the catalytic activity of nanoenzymes in neutral environments, we prepare a novel multifunctional Fe3O4@Ag@ indocyanine green/adenosine triphosphate peroxidase nanoenzymes for synergistic antibacterial activity. ICG (Indocyanine Green) and ATP (Adenosine triphosphate) are adsorbed on the surface of Fe3O4@Ag through electrostatic adsorption to form its structure. The cell viability remained above 90%, indicating its good biocompatibility. By complexing ATP with nanoenzymes to participate in single electron transfer and binding with Fe (II), ATP promotes the sudden release of hydroxyl radical (·OH) from the system, successfully transferring Fe3O4@Ag the peroxidase activity of nanoenzymes extends to neutral pH. By utilizing ICG as a photosensitizer and a sonosensitizer, under the combined treatment of near-infrared light and ultrasound, the photodynamic therapy (PDT)/photothermal therapy (PTT)/sonodynamic therapy (SDT) functions can be achieved, achieving multifunctional synergistic antibacterial effects. In a neutral environment, its bactericidal efficiency against Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus) is 99.9% and 99.7%, respectively, providing a new multi-mode synergistic antibacterial strategy for bacterial infections.

The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in the microbiome has been implicated in numerous dermatological conditions, including acne, eczema, psoriasis, and rosacea. Acne, the most prevalent skin condition, affects up to 85% of individuals at some point in their lives, while eczema and psoriasis impose significant public health and economic burdens. The composition of the skin microbiome varies across skin types and anatomical sites, with sebaceous, moist, and dry areas fostering distinct microbial communities. Emerging therapeutic strategies such as microbiome-targeted treatments offer novel avenues for addressing skin diseases. Among these approaches, postbiotics have gained significant attention for their safety and efficacy. Unlike probiotics, postbiotics are non-viable microbial cells or their metabolites, which reduce safety concerns while providing functional benefits such as UV protection and wound healing. This review consolidates current insights into the role of the skin microbiome in health and disease, emphasizing postbiotics as a promising therapeutic strategy by exploring the clinical and commercial potential of microbiome-based treatments, particularly postbiotics, and their ability to redefine dermatological care and improve patient outcomes.

The skin microbiome is integral to maintaining skin homeostasis and is involved in the pathogenesis of acne. Emerging evidence supporting the 'brain-skin axis' suggests that psychological stress may exacerbate acne. Both negative emotional states and acne are highly prevalent among adolescents. Although research has begun to explore this relationship, the role of the skin microbiome in adolescents experiencing emotional disturbances and acne remains poorly understood.

166 adolescents aged 15-18 were divided into four distinct groups based on their emotional health and acne severity: no acne or negative emotions (NC), acne without negative emotions (NS), negative emotions without acne (YC), and acne with negative emotions (YS). Skin samples were collected from each participant's forehead and analyzed using high-throughput sequencing techniques, followed by comprehensive bioinformatics analyses to evaluate the microbial composition and diversity across the different groups.

Adolescents with both acne and negative emotions exhibited significantly higher acne severity (IGA 2.675 ± 0.090) compared to the group with acne but without negative emotions (IGA 1.952 ± 0.136). Distinct microbial community patterns emerged among the groups, with acne-affected individuals displaying increased α-diversity. Additionally, negative emotions were associated with heightened β-diversity differences between acne-affected individuals. The predominant bacterial phyla identified were Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria, with Acinetobacter being more abundant, and Roseomonas and Cutibacterium being less prevalent in adolescents experiencing negative emotions.

This study revealed that the bacterial biomarkers of the disease change when acne is accompanied by negative emotions. Cutibacterium, Acinetobacter, and Roseomonas may be key contributors to acne exacerbation. These findings underscore the importance of considering both emotional and microbiological factors in the management of adolescent acne, particularly within the context of the brain-skin connection.

Up to 95% of women during and after radiation therapy (RT) for breast cancer have reported cutaneous toxicity. However, the biologic link between skin microbiome and skin toxicities from RT remains largely unknown. This study aimed to assess the associations of skin microbiome with clinician- and patient-reported skin toxicities and inflammatory markers in women with breast cancer receiving RT.

A prospective, longitudinal study was conducted at a single institution. Thirty-two women with breast cancer undergoing moderately hypofractionated RT for 3 to 4 weeks after breast conserving surgery were enrolled and 30 of them were analyzed. A total of 240 swabs for skin microbiome and 120 plasma samples were collected pre-RT baseline (T1), week-1 of RT (T2), week-3 of RT (T3), and 3 months post-RT (T4), from the cancer-affected and contralateral healthy breasts. Skin microbiome specimens were processed using 16S V1-V3 sequencing.

Differences in skin microbiome of the treated breasts during RT (T2 and T3) were observed compared with the skin microbiome of pre-RT baseline breasts (T1) and contralateral, healthy breasts, with the affected breasts having an increased abundance of pathogenetic Finegoldia (P = .001), Dermacoccus (P = .01), and Variovorax (P = .003) during RT. Longitudinal analysis showed that decreased Variovorax but increased Staphylococcus were associated with increased clinician-reported grade 2 pruritus (P = .002) and dermatitis (P = .012), and increased patient-reported moderate or severe darkened skin (P = .002) and itchy skin (P = .012). Additionally, the plasma interferon gamma was associated with changes in skin microbiome in women with breast cancer undergoing RT.

This study shows changes in the skin microbiome during well-tolerated moderately hypofractionated breast RT. The skin microbiome return toward baseline appears to associate with improvement of clinician- and patient-reported skin toxicities post-treatment. Although there were few high-grade toxicities observed among frequently prescribed courses of hypofractionated whole breast RT, changes in skin microbiome may be of interest as further targets of symptomatic relief or intervention as ultrahypofractionated courses become more common.

In addition to producing melanin to protect epidermal keratinocytes against DNA damage, melanocytes may have important roles in strengthening innate immunity against pathogens. We have developed a functional, pigmented, human full-thickness 3D skin equivalent to determine whether the presence of melanocytes impacts epidermal bacterial growth and regulates the expression of genes involved in the immune response. We introduced primary epidermal melanocytes to construct a 3-cell full-thickness skin equivalent with primary dermal fibroblasts and epidermal keratinocytes. Immunohistochemistry verified the appropriate ratio and spatial organisation of melanocytes. Alpha-MSH induced melanogenesis, confirming an appropriate physiological response. We compared this 3-cell skin equivalent with the 2-cell version without melanocytes in response to inoculation with 3 species of bacteria: Staphylococcus epidermidis, Corynebacterium striatum, and Cutibacterium acnes. There was a significant decrease in the colonisation of bacteria in the skin equivalents containing functional melanocytes. There was increased expression of immune-response genes (S100A9, DEFB4A, IL-4R) following microorganism exposure; however, there were marked differences between the unpigmented and pigmented skin equivalents. This physiologically relevant human 3D-skin equivalent opens up new avenues for studying complex skin pigmentation disorders, melanoma, and UV damage, as well as the rapidly evolving field of the skin microbiome and the balance between commensal and pathogenic species.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.

Foot ulcers are a common and feared complication for people with diabetes because 20% of foot ulcers become infected and lead to a lower extremity amputation.

To evaluate the effect of daily foot care using chlorhexidine wipes vs soap-and-water wipes for 1 year on the risk of developing new foot complications in veterans with diabetes.

This double-blind, placebo-controlled, phase 2b randomized clinical trial was conducted at the Baltimore Veterans Affairs (VA) Medical Center between January 2019 to January 2023. Veterans were eligible if they had a diabetes diagnosis, were at high risk for diabetic foot complications, were ambulatory, had both feet, and did not have a current foot infection. Participants were randomly assigned 1:1 to receive either soap-and-water wipes (control group) or 2% chlorhexidine wipes (chlorhexidine group). Intention-to-treat data analysis was conducted from October 5, 2023, to April 24, 2024.

Daily use of a 2% chlorhexidine wipe or a soap-and-water wipe on the feet for 1 year. Wipes were nearly identical in color, size, shape, thickness, feel, and scent. Both chlorhexidine and control groups received the same lotion for application on the feet after wipe use and education on foot self-care.

The primary outcome was time in days from randomization to new foot complication, including chronic foot ulcer, foot infection, or foot amputation.

A total of 175 participants (170 males [97%]; mean [SD] age at enrollment, 68 [9] years; 1 Asian [1%], 117 Black or African American [67%], 53 White [30%] individuals) were randomly assigned to the chlorhexidine group (n = 88) or the control group (n = 87). Twelve participants (14%) in the chlorhexidine group and 14 participants (16%) in the control group developed a new foot complication within 1 year. Median (IQR) time from randomization to development of a new foot complication was 232 (115-315) days. The reduction in hazard of new foot complications in the chlorhexidine group compared with the control group was not significant (hazard ratio, 0.83; 95% CI, 0.39-1.80). The intervention was well tolerated, with 145 participants (83%) continuing it over the study period. Sixty adverse events occurred, but none was related to the study products or procedures.

This randomized clinical trial found that daily use of chlorhexidine wipes for foot washing for 1 year did not lead to a significant reduction in the risk of new foot complications compared with daily use of soap-and-water wipes. The intervention was well tolerated, and the trial provides important lessons for future studies on diabetic foot ulcer prevention.

ClinicalTrials.gov Identifier: NCT03503370.

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

The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection1. However, the scope and purpose of this anticommensal immune programme are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain of S. epidermidis in which the parallel β-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge. A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labelled commensal elicits high antibody titres under conditions of physiologic colonization, including a robust IgA response in the nasal and pulmonary mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a new form of topical vaccination.

Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder in which the skin is affected by microbial dysbiosis. The role of commensal skin microbiota in AD is of great interest. Extracellular vesicles (EVs) are important regulators of skin homeostasis and pathology. The mechanism of preventing AD pathogenesis through commensal skin microbiota-derived EVs remains poorly understood. In this study, we investigated the role of commensal skin bacterium Staphylococcus epidermidis-derived EVs (SE-EVs). We showed that SE-EVs significantly decreased the expression of proinflammatory genes (TNFα, IL1β, IL6, IL8, and iNOS) through lipoteichoic acid and increased the proliferation and migration of calcipotriene (MC903)-treated HaCaT keratinocytes. Furthermore, SE-EVs increased the expression of human β-defensins 2 and 3 in MC903-treated HaCaT cells through toll-like receptor 2, enhancing resistance to S. aureus growth. In addition, topical SE-EV application remarkably attenuated inflammatory cell infiltration (CD4+ T cells and Gr1+ cells), T helper 2 cytokine gene expression (Il4, Il13, and Tlsp), and IgE levels in MC903-induced AD-like dermatitis mice. Intriguingly, SE-EVs induced IL-17A+ CD8+ T-cell accumulation in the epidermis, which may represent heterologous protection. Taken together, our findings showed that SE-EVs reduced AD-like skin inflammation in mice and may potentially be a bioactive nanocarrier for the treatment of AD.

Public health alarm concerning the emerging fungus Candida auris is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of C. auris with its relative C. albicans, quantifying skin fungal persistence and distribution and immune composition and positioning. C. auris displayed a higher propensity to colonize hair follicles and avidly bound to human hair. While C. albicans triggered an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggered a type 1, IFNγ-driven immune response targeting hair follicles. Rather than promoting fungal clearance, IFNγ enhanced C. auris skin colonization by acting directly on keratinocytes impairing epithelial barrier integrity and repressing antifungal defense programs. C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles.

The microbiome is a highly complex and diverse symbiotic component that undergoes dynamic changes with the organismal aging. Microbial perturbations, termed dysbiosis, exert strong influence on dysregulating the bone marrow niche and subsequently promoting the aging of hematopoietic and immune system. Accumulating studies have revealed the substantial impact of intestinal microbiome on the initiation and progression of age-related hematologic alteration and diseases, such as clonal hematopoiesis and blood cancers. Current therapeutic approaches to restore the altered microbiome diversity target specific pathobionts and are demonstrated to improve clinical outcomes of antihematologic malignancy treatments. In this review, we discuss the interplay between the microbiome and the hemato-immune system during aging process. We also shed light on the emerging therapeutic strategies to tackle the dysbiosis for amelioration of aging and disease progression.

Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin.

To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States.

Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status.

This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.

In mucosal barriers, tissue cells and leukocytes collaborate to form specialized niches that support host-microbiome symbiosis. Understanding the spatial organization of these barriers is crucial for elucidating the mechanisms underlying health and disease. The gingiva, a unique mucosal barrier with significant health implications, exhibits intricate tissue architecture and likely contains specialized immunological regions. Through spatial transcriptomic analysis, this study reveals distinct immunological characteristics between the buccal and palate regions of the murine gingiva, impacting natural alveolar bone loss. The microbiota primarily affects gingival immunity in the buccal region. Additionally, a significant influence of the microbiota on the junctional epithelium facing the oral biofilm offers new insights into neutrophil recruitment. The microbiota also regulates the proliferation and barrier-sealing function of the gingival epithelium. This underscores the presence of immunological niches in the gingiva, with the microbiota differentially influencing them, highlighting the high complexity of this oral mucosal barrier.

Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.

The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse skin with the model human skin commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less is known about concurrent skin damage and exposure to commensal microbes, despite growing interest in interventional probiotic therapy. In this study, we address this open question by applying commensal skin bacteria at a high dose to abraded skin. Although depletion of the skin microbiome through antibiotics delayed repair from damage, probiotic-like application of commensals-including the mouse commensal Staphylococcus xylosus, 3 distinct isolates of S. epidermidis, and all other tested human skin commensals-also significantly delayed barrier repair. Increased inflammation was observed within 4 hours of S. epidermidis exposure and persisted through day 4, at which point the skin displayed a chronic wound-like inflammatory state with increased neutrophil infiltration, increased fibroblast activity, and decreased monocyte differentiation. Transcriptomic analysis suggested that the prolonged upregulation of early canonical proliferative pathways inhibited the progression of barrier repair. These results highlight the nuanced role of members of the skin microbiome in modulating barrier integrity and indicate the need for caution in their development as probiotics.

Alopecia areata (AA) is an autoimmune disease causing non-scarring hair loss, with both genetic and environmental factors implicated. Recent research highlights a possible role for scalp microbiota in influencing both local and systemic inflammatory responses, potentially impacting AA progression. This study examines the link among scalp microbiota imbalances, AA severity, and systemic inflammation.

We conducted a cross-sectional study with 24 participants, including patients with AA of varying severities and healthy controls. Scalp microbial communities were analyzed using swab samples and ion torrent sequencing of the 16S rRNA gene across multiple hypervariable regions. We explored correlations among bacterial abundance, microbiome metabolic pathways, and circulating inflammatory markers.

Our findings reveal significant dysbiosis in the scalp microbiota of patients with AA compared to healthy controls. Severe AA cases had an increased presence of pro-inflammatory microbial taxa like Proteobacteria, whereas milder cases had higher levels of anti-inflammatory Actinobacteria. Notable species differences included abundant gram-negative bacteria such as Alistipes inops and Bacteroides pleibeius in severe AA, contrasted with Blautia faecis and Pyramydobacter piscolens predominantly in controls. Significantly, microbial imbalance correlated with AA severity (SALT scores) and systemic inflammatory markers, with elevated pro-inflammatory cytokines linked to more severe disease.

These results suggest that scalp microbiota may play a role in AA-related inflammation, although it is unclear whether the shifts are a cause or consequence of hair loss. Further research is needed to clarify the causal relationship and mechanisms involved.

The role of the skin microbiome in resistance and susceptibility of wildlife to fungal pathogens has been examined from a taxonomic perspective but skin microbial function, in the context of fungal infection, has yet to be studied. Our objective was to understand effects of a bat fungal pathogen site infection status and course of invasion on skin microbial function. We sampled seven hibernating colonies of Myotis lucifugus covering three-time points over the course of Pseudogymnoascus destructans (Pd) invasion and white nose syndrome (pre-invasion, epidemic, and established). Our results support three new hypotheses about Pd and skin functional microbiome: (1) there is an important effect of Pd invasion stage, especially at the epidemic stage; (2) disruption by the fungus at the epidemic stage could decrease anti-fungal functions with potential negative effects on the microbiome and bat health; (3) the collection site might have a larger influence on microbiomes at the pre-invasion stage rather than at epidemic and established stages. Future studies with larger sample sizes and using meta-omics approaches will help confirm these hypotheses, and determine the influence of the microbiome on wildlife survival to fungal disease.

The cause of keloids remains unclear, but studies suggest a link between skin microbiota and keloid formation. However, the causal relationship has not been confirmed. This study utilized Genome-Wide Association Studies (GWAS) data from 2 population-based German cohorts, comprising a total of 1656 skin samples. To bolster the reliability of our results, we incorporated GWAS data from 3 keloid cohorts, encompassing 2555 patients and 870,556 controls (GWAS ID: keloid1, ebi-a-GCST90018874; keloid2, bbj-a-131; keloid3, ebi-a-GCST90018654). Subsequently, we employed bidirectional 2-sample Mendelian randomization (MR) analysis to probe the causal relationship between the variables. The primary method employed was the inverse-variance weighted (IVW) method, supported by heterogeneity analysis, horizontal pleiotropy testing, outlier detection, and "leave-one-out" sensitivity analysis. By synthesizing the results from 3 groups of MR analyses, we discovered a negative causal association between a.ASV063 [Finegoldia (unc.)] located on the volar forearm and keloid disease (IVW (keloid1) odds ratio (OR): 0.939, 95% confidence interval (CI): 0.886-0.994, P = .032; IVW (keloid2) OR: 0.897, 95% CI: 0.813-0.990, P = .031; IVW (keloid3) OR: 0.900, 95% CI: 0.825-0.981, P = .017). Similarly, a negative causal relationship may also exist between the genus: Bacteroides from the antecubital fossa and keloid disease (IVW (keloid1) OR: 0.928, 95% CI: 0.884-0.973, P = .002; IVW (keloid2) OR: 0.891, 95% CI: 0.820-0.968, P = .007; IVW (keloid3) OR: 0.918, 95% CI: 0.849-0.992, P = .030). Additionally, no reverse causation was found, with all analyses showing no signs of horizontal pleiotropy or heterogeneity. This study offers new insights for the prevention and treatment of keloids.

Psoriasis is a common chronic inflammatory skin disease, associated with significant morbidity and a considerable negative impact on the patients' quality of life. The complex pathogenesis of psoriasis is still incompletely understood. Genetic predisposition, environmental factors like smoking, alcohol consumption, psychological stress, consumption of certain drugs, and mechanical trauma, as well as specific immune dysfunctions, contribute to the onset of the disease. Mounting evidence indicate that skin dysbiosis plays a significant role in the development and exacerbation of psoriasis through loss of immune tolerance to commensal skin flora, an altered balance between Tregs and effector cells, and an excessive Th1 and Th17 polarization. While the implications of skin dysbiosis in psoriasis pathogenesis are only starting to be revealed, the progress in the characterization of the skin microbiome changes in psoriasis patients has opened a whole new avenue of research focusing on the modulation of the skin microbiome as an adjuvant treatment for psoriasis and as part of a long-term plan to prevent disease flares. The skin microbiome may also represent a valuable predictive marker of treatment response and may aid in the selection of the optimal personalized treatment. We present the current knowledge on the skin microbiome changes in psoriasis and the results of the studies that investigated the efficacy of the different skin microbiome modulation strategies in the management of psoriasis, and discuss the complex interaction between the host and skin commensal flora.

A novel bacterial isolate A520T (A520T = CBAS 737T = CAIM 1944T) was obtained from the skin of bandtail puffer fish Sphoeroides spengleri (Tetraodontidae Family), collected in Arraial do Cabo (Rio de Janeiro, Brazil). A520T is Gram-stain-negative, flagellated and aerobic bacteria. Optimum growth occurs at 25-30 °C in the presence of 3% NaCl. The genome sequence of the novel isolate consisted of 4.5 Mb (4082 coding genes and G+C content of 41.1%). The closest phylogenetic neighbor was Pseudoalteromonas shioyasakiensis JCM 18891T (97.9% 16S rRNA sequence similarity, 94.8% Average Amino Acid Identity, 93% Average Nucleotide Identity and 51.8% similarity in Genome-to-Genome-Distance). Several in silico phenotypic features are useful to differentiate A520T from its closest phylogenetic neighbors, including trehalose, D-mannose, cellobiose, pyrrolidonyl-beta-naphthylamide, starch hydrolysis, D-xylose, lactose, tartrate utilization, sucrose, citrate, glycerol, mucate and acetate utilization, malonate, glucose oxidizer, gas from glucose, nitrite to gas, L-rhamnose, ornithine decarboxylase, lysine decarboxylase and yellow pigment. The genome of the novel species contains 3 gene clusters (~ 66.81 Kbp in total) coding for different types of bioactive compounds that could indicate ecological roles pertaining to the bandtail puffer fish host. Based on genome-based taxonomic approach, strain A520T (A520T = CBAS 737T = CAIM 1944T) is proposed as a new species, Pseudoalteromonas simplex sp. nov.

The cutaneous microbiome represents a highly dynamic community of bacteria, fungi and viruses. Scientific evidence, particularly from the last two decades, has revealed that these organisms are far from being inconsequential microscopic hitchhikers on the human body, nor are they all opportunistic pathogens waiting for the chance to penetrate the skin barrier and cause infection. In this review, we will describe how dermatological diseases have been found to be associated with disruptions and imbalances in the skin microbiome and how this new evidence had shaped the diagnosis and clinical practice relating to these disorders. We will identify the microbial agents which have been found to directly exacerbate skin diseases, as well as those which can ameliorate many of the symptoms associated with dermatological disorders. Furthermore, we will discuss the studies which suggest that bacteriotherapy, either by topical use of probiotics or by bacteria-derived compounds, can rectify skin microbial imbalances, thereby offering a promising alternative to antibiotic treatment and reducing the risks of antibiotic resistance.

In naive individuals, sensory neurons directly detect and respond to allergens, leading to both the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response1,2. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch3-7. Although these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naive state is unknown. Here we describe a γδ T cell-IL-3 signalling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal γδ T cell subset8, termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This γδ T cell-IL-3 signalling axis further acts by means of STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens on first exposure. This pathway may explain individual differences in allergic susceptibility and opens new therapeutic avenues for treating allergic diseases.

Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.

Despite relevant research, the relationship between skin microbiomes and prostate cancer remains controversial. This study utilizes bidirectional Mendelian randomization (MR) analysis combined with meta-analysis to explore the potential link between the two.

This study aims to identify the causal relationship between 150 skin microbiomes and prostate cancer (PCa) using bidirectional Mendelian randomization (MR) and meta-analysis.

This study employed a comprehensive Bidirectional Two-sample MR analysis using publicly available genetic data to ascertain the relationship between 150 skin microbiomes and PCa. We conducted extensive sensitivity analyses, tests for heterogeneity, and assessments of horizontal pleiotropy to ensure the accuracy of our results. Subsequently, we conducted a meta-analysis to strengthen our conclusions' robustness further. Finally, we performed reverse causal verification on the positive skin microbiomes and PCa.

After conducting a meta-analysis and multiple corrections of the MR analysis results, our findings reveal a correlation between Neisseria in dry skin and PCa risk, identifying it as a risk factor. The IVW result shows an Odds Ratio (OR) of 1.009 (95% Confidence Interval [CI]: 1.004-1.014, P = 0.027). Furthermore, the reverse MR analysis indicates the absence of an inverse causal relationship between the two. Apart from the identified skin microbiome, no significant associations were found between the other microbiomes and PCa.

The study identified a correlation between Neisseria in dry skin, one of the 150 skin microbiomes, and the risk of developing PCa, establishing it as a risk factor for increased susceptibility to PCa.

Microbial exposures during infancy shape the development of the microbiome, the collection of microbes living in and on the body, which in turn directs immune system training. Newborns acquire a substantial quantity of microbes during birth and throughout infancy via exposure to microbes in the physical and social environment. Alterations to early life microbial environments may give rise to mismatches, where environmental, cultural and behavioral changes that outpace the body's adaptive responses can lead to adverse health outcomes, particularly those related to microbiome development and immune system regulation.

This study explored the development of the skin microbiome among infants born in Chicago, USA. We collected skin swab microbiome samples from 22 mother-infant dyads during the first 48 h of life and again at 6 weeks postpartum. Mothers provided information about social environments and hygiene behaviors that may impact infants' microbial exposures.

Analysis of amplicon bacterial gene sequencing data revealed correlations between infant skin bacterial abundances shortly after birth and factors such as antibiotic exposure and receiving a bath in the hospital. The composition of the infant microbiome at 6 weeks of age was associated with interactions with caregivers and infant feeding practices. We also found shifts in maternal skin microbiomes that may reflect increased hygiene practices in the hospital.

Our data suggest that factors related to the birth and household environment can impact the development of infant skin microbiomes and point to practices that may produce mismatches for the infant microbiome and immune system.

Leishmania is an intracellular protozoan transmitted by sand fly vectors; it causes cutaneous, mucocutaneous, or visceral disease. Its growth and survival are impeded by type 1 T helper cell responses, which entail interferon (IFN)-γ-mediated macrophage activation. Leishmania partially escapes this host defense by triggering immune cell and cytokine responses that favor parasite replication rather than killing. Novel methods for in situ analyses have revealed that the pathways of immune control and microbial evasion are strongly influenced by the tissue context, the micro milieu factors, and the metabolism at the site of infection, which we collectively term the 'immunomicrotope'. Understanding the components and the impact of the immunomicrotope will enable the development of novel strategies for the treatment of chronic leishmaniasis.