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Skin is the largest organ in the human body, and the interplay between the environment factors and human skin leads to some skin diseases, such as acne, psoriasis, and atopic dermatitis. As the first line of human immune defense, skin plays significant roles in human health via preventing the invasion of pathogens that is heavily influenced by the skin microbiota. Despite being a challenging niche for microbes, human skin is colonized by diverse commensal microorganisms that shape the skin environment. The skin microbiota can affect human health, and its imbalance and dysbiosis contribute to the skin diseases. This review focuses on the advances in our understanding of skin microbiota and its interaction with human skin. Moreover, the potential roles of microbiota in skin health and diseases are described, and some key species are highlighted. The prevention, diagnosis and treatment strategies for microbe-related skin diseases, such as healthy diets, lifestyles, probiotics and prebiotics, are discussed. Strategies for modulation of skin microbiota using synthetic biology are discussed as an interesting venue for optimization of the skin-microbiota interactions. In summary, this review provides insights into human skin microbiota recovery, the interactions between human skin microbiota and diseases, and the strategies for engineering/rebuilding human skin microbiota.

Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species of bacteria produce Shiga toxins (Stxs), a phage-encoded exotoxin inhibiting protein synthesis in host cells that are primarily responsible for bacterial virulence. Although most studies have focused on the pathogenic roles of Stxs as harmful substances capable of inducing cell death and as proinflammatory factors that sensitize the host target organs to damage, less is known about the interface between the commensalism of bacterial communities and the pathogenicity of the toxins. The gut contains more species of bacteria than any other organ, providing pathogenic bacteria that colonize the gut with a greater number of opportunities to encounter other bacterial species. Notably, the presence in the intestines of pathogenic EHEC producing Stxs associated with severe illness may have compounding effects on the diversity of the indigenous bacteria and bacterial communities in the gut. The present review focuses on studies describing the roles of Stxs in the complex interactions between pathogenic Shiga toxin-producing E. coli, the resident microbiome, and host tissues. The determination of these interactions may provide insights into the unresolved issues regarding these pathogens.

Objective: Immune checkpoint inhibitors have revolutionized cancer therapy for multiple types of solid tumors, but as expected, alarge percentage of patients do not show durable responses. Biomarkers that can predict clinical responses to immunotherapies atdiagnosis are therefore urgently needed. Herein, we determined the associations between baseline gut commensal microbes and theclinical treatment efficiencies of patients with thoracic neoplasms during anti-programmed death protein 1 (PD-1) therapy. Methods: Forty-two patients with advanced thoracic carcinoma who received anti-PD-1 treatment were enrolled in the study. Baselineand time-serial stool samples were analyzed using 16S ribosomal RNA gene sequencing. Tumor responses, patient progression-freesurvival, and overall survival were used to measure clinical outcomes. Results: The diversities of the baseline gut microbiota were similar between responders (n = 23) and nonresponders (n = 19).The relative abundances of the Akkermansiaceae, Enterococcaceae, Enterobacteriaceae, Carnobacteriaceae and Clostridiales Family XIbacterial families were significantly higher in the responder group. These 5 bacterial families acted as a commensal consortiumand better stratified patients according to clinical responses (P = 0.014). Patients with a higher abundance of commensal microbeshad prolonged PFS (P = 0.00016). Using multivariable analysis, the abundance of the commensal consortium was identified as anindependent predictor of anti-PD-1 immunotherapy in thoracic neoplasms (hazard ratio: 0.17; 95% confidence interval: 0.05–0.55;P = 0.003). Conclusions: Baseline gut microbiota may have a critical impact on anti-PD-1 treatment in thoracic neoplasms. The abundance ofgut commensal microbes at diagnosis might be useful for the early prediction of anti-PD-1 immunotherapy responses.

Commensal microbes have increasingly been found to be involved in the development and progression of cancer. The recent discovery of the urinary microbiome bolstered the notion that microbes might play a role in bladder cancer. Although microbial involvement in bladder neoplastic transformation and metastatic progression, except schisto somiasis, has not been established, accumulating research suggests that dysbiosis of the urinary microbiome can produce a chronically inflammatory urothelial microenvironment and lead to bladder cancer. In this review, we describe how the urinary microbiome might facilitate the development of bladder cancer by altering the host immune system and the kind of cytokines that are directly involved in these responses. We investigated the therapeutic possibilities of modulating the urinary microbiome, including immune checkpoint therapy. The responsiveness of patients to intravesical Bacillus Calmette-Guerin therapy was evaluated with respect to microbiome composition. We conclude by noting that the application of microbes to orchestrate the inflammatory response in the bladder may facilitate the development of treatments for bladder cancer.

Aronia berry (Aronia melanocarpa) is rich in polyphenolic compounds with reported antioxidant and prebiotic activities, including potential life‐extending effects. Although previous studies have highlighted its impact on the gut microbiota, the extent to which commensal microbes contribute to its longevity effects remains poorly understood. Here, we aimed to determine whether the lifespan‐ and health‐promoting effects of Aronia berry are mediated by commensal microbes and to elucidate the underlying mechanisms. To address this, we investigated the effects of Aronia berry supplementation (5 µg/mL in food) on lifespan and physiological traits in Drosophila melanogaster under both conventional and axenic (germ‐free) conditions. Assays included survival, antioxidant activity, microbial load, and immune gene expression. Aronia berry significantly extended the lifespan of conventional flies but failed to do so in axenic flies, suggesting a microbiota‐dependent mechanism. In conventional flies, supplementation of Aronia berry reduced microbial load without altering diversity, enhanced oxidative stress resistance, and upregulated antimicrobial peptide genes via Toll pathway activation. These effects were not observed in axenic flies. Genetic activation of the Toll pathway mimicked the Aronia ‐induced microbial suppression and lifespan extension, suggesting a causal role for Toll signaling in mediating the health benefits of Aronia berry. Our findings demonstrate that Aronia berry exerts its longevity‐promoting effects through commensal microbe‐mediated activation of host immunity and oxidative stress reduction. This study highlights the essential role of gut microbes in mediating the health benefits of polyphenol‐rich diets and offers insights into dietary strategies for promoting healthy aging. Aronia berry extract extends lifespan in Drosophila melanogaster by modulating commensal microbes, reducing oxidative stress, and activating the immune system via the Toll pathway. Its longevity effects are dependent on gut microbiota, highlighting the interplay between polyphenols, microbes, and aging.

Background: Commensal microbiota live in their host with a symbiotic relationship that affects the host’s health and physiology. Many studies showed that microbial load and composition were changed by aging and observed that increasing the abundance and changing the composition of commensal microbes had detrimental effects on host lifespan. We hypothesized that dysbiosis of the intestinal microbiota leads to systemic effects in aging flies as a result of the increased intestinal permeability. Methods: We used the fruit fly, Drosophila melanogaster, laboratory strains w1118, as a model system with many advantages for microbe–host studies. Results: The incidence of intestinal dysfunction was increased with age, and intestinal dysfunction increased the permeability of the fly intestine to resident microbes. The lifespan of flies with an intestinal barrier dysfunction was increased by removal of the microbes. Interestingly, some bacteria were also found in the hemolymph of flies with intestinal barrier dysfunction. Conclusion: Our findings suggest the possibility that, as the host ages, there is an increase in intestinal permeability, which leads to an increased intestinal microbial load and a reduction in the host lifespan. Our data therefore indicate a connection between commensal microbes and host lifespan.

Microorganisms have coevolved diverse mechanisms to impair host defenses. A major one, superantigens, can result in devastating effects on the immune system.While all known superantigens induce vast immune cell proliferation and come from opportunistic pathogens, recently, proteins with similar broad specificity to antibody variable (V) domain families were identified in a commensal microbiota. These proteins, identified in the human commensal Ruminococcus gnavus, are called immunoglobulin-binding protein (Ibp) A and B and have been shown to activate B cells in vitro expressing either human VH3 or murine VH5/6/7. Here, we provide molecular and functional studies revealing the basis of this Ibp/immunoglobulin (Ig) interaction. The crystal structure and biochemical assays of a truncated IbpA construct in complex with mouse VH5 antigen-binding fragment (Fab) shows a binding of Ig heavy chain framework residues to the Ibp Domain D and the C-terminal heavy chain binding domain (HCBD). We used targeted mutagenesis of contact residues and affinity measurements and performed studies of the Fab-IbpA complex to determine the stoichiometry between Ibp and VH domains, suggesting Ibp may serve to cluster full-length IgA antibodies in vivo. Furthermore, in vitro stimulation experiments indicate that binding of the Ibp HCBD alone is sufficient to activate responsive murine B cell receptors. The presence of these proteins in a commensal microbe suggest that binding a broad repertoire of immunoglobulins, particularly in the gut/microbiome environment, may provide an important function in the maintenance of host/microbiome homeostasis contrasting with the pathogenic role of structurally homologous superantigens expressed by pathogens.

Ionizing radiation induces biological/physiological changes and affects commensal microbes, but few studies have examined the relationship between the physiological changes induced by irradiation and commensal microbes. This study investigated the role of commensal microbes in the γ-ray irradiation-induced physiological changes in Drosophila melanogaster. The bacterial load was increased in 5 Gy irradiated flies, but irradiation decreased the number of operational taxonomic units. The mean lifespan of conventional flies showed no significant change by irradiation, whereas that of axenic flies was negatively correlated with the radiation dose. γ-Ray irradiation did not change the average number of eggs in both conventional and axenic flies. Locomotion of conventional flies was decreased after 5 Gy radiation exposure, whereas no significant change in locomotion activity was detected in axenic flies after irradiation. γ-Ray irradiation increased the generation of reactive oxygen species in both conventional and axenic flies, but the increase was higher in axenic flies. Similarly, the amounts of mitochondria were increased in irradiated axenic flies but not in conventional flies. These results suggest that axenic flies are more sensitive in their mitochondrial responses to radiation than conventional flies, and increased sensitivity leads to a reduced lifespan and other physiological changes in axenic flies.

Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.

Although mechanisms operative in the induction and maintenance of specific, adaptive immunity, including ‘cognate’ B/T interactions, have been extensively studied and defined, we still know little about the mechanisms operative in developing and maintaining B- and T-cell dependent ‘natural’ immunity. Particularly, we are still rather ignorant concerning gut microbial/gut or systemic APC, T cell and B cell interactions that lead to lymphoid cell mediated ‘natural’ immunity: specific or broadly reactive, activation via TCR and BCR and/or via other receptors such as the TLR series, and whether T/B interactions are operative at this level? Here we will address: (1) the general role of gut microbes in the development and maintenance of the intestinal, humoral immune system; (2) the general role of gut microbes in the development of B1 cell mediated, ‘natural’ gut IgA and the dependence of these B1 cells on bystander T cell help; (3) the relative contributions of B1 versus B2 cells to gut ‘natural’ and specific IgA responses; (4) the role for particular ‘normal’ gut microbes in the initiation of inflammatory bowel diseases (IBD) in mice with a dysregulated immune system; and (5) the possible roles of gut microbes in facilitating oral tolerance, a mechanism likely operative in forestalling or ameliorating IBD. A central theme of this paper is to attempt to define the specificities of activated, functional CD4+ T cells in the gut for Ags of particular, usually benign gut microbes. We will also consider the still-unresolved issue of whether the contributions of B1-derived IgA in the gut to the ‘natural’ Ab pool are Ag-selected and driven to proliferation/differentiation or whether the main stimuli are not via BCRs but rather other receptors (TLRs, etc.). The main experimental approach has been to use antigen-free, germ-free, or gnotobiotic (mono- or oligo-associated with precisely known bacterial species) mice.