Qing Li

Background: Gut microbiota dysbiosis is implicated in dermatoses, including acne vulgaris. However, gut microbial and metabolomic profiles in acne remain uncharacterized. Methods: We performed metagenomic and metabolomic analyses on fecal samples from 29 acne patients and 20 healthy controls. Functional annotations utilized multiple databases. Integrated metagenomic-metabolomic analysis was conducted to identify metabolites, and their effects were subsequently validated in a mouse acne model. Finally, a five-fold cross-validated random forest model evaluated discriminatory capacity of microbial, metabolic, and multi-omics signatures for acne and its subtypes. Results: Acne patients exhibited reduced gut microbial diversity and decreased abundance of beneficial genera (eg, Blautia, Faecalibacterium) and species (eg, Anaerotardibacter muris, Firmicutes bacterium CAG:321, Clostridium sp. CAG:245, Ruminococcus sp. OM06-36AC). Differentially enriched microbial pathways involved amino acid metabolism. Integrated analysis revealed positive correlations between the key microbes driving the selected pathways and the associated metabolites which promoted the growth of C. acnes. The integrated multi-omics model yielded high diagnostic accuracy (validation AUC=0.921, test AUC=0.915), outperforming single-omic models, showed optimal gender discrimination (test AUC=1.00) and subtype-specific predictive efficacy, with key microbial and metabolite biomarkers identified for acne subtype classification and disease progression regulation. Conclusion: Acne vulgaris demonstrates distinct gut microbiota and metabolite signatures. Our integrated data suggest that gut microbiota may influence acne development via metabolic changes, and some of these metabolites might possess acne‑promoting properties.

Background: Gut microbiota can modulate cancer immunotherapy and enhance the efficacy of programmed cell death protein 1 (PD-1) blockade in tumors, yet the responsible microbes and underlying mechanisms remain incompletely understood. Methods: Publicly available anti-PD-1-treated melanoma microbiome cohorts were reanalyzed. Causal validation was performed using oral Blautia coccoides ( B. coccoides ) supplementation in B16-F10 melanoma-bearing mice. Untargeted and targeted liquid chromatography-tandem mass spectrometry-based metabolomics, CD8 ⁺ T-cell depletion, receptor identification and binding analyses, and downstream transcriptomic and biochemical assays were used to identify the key metabolite and investigate its mechanism of action. Results: We identified Blautia as enriched in melanoma patients responding to immune checkpoint inhibitors, with higher abundance associated with non-progression. In melanoma-bearing mice, oral B. coccoides suppressed tumor growth and increased intratumoral effector CD8 ⁺ T cells. Metabolomic profiling identified acetate as a prominent B. coccoides -associated metabolite. Acetate enhanced CD8 ⁺ T-cell effector function. CD8 ⁺ T-cell depletion largely abrogated the antitumor effects of both B. coccoides and acetate, supporting a central role for CD8 ⁺ T cells. Mechanistically, these findings support a model in which acetate is associated with a TLR3-linked signaling pathway in CD8 ⁺ T cells, accompanied by PI3K/Akt activation and enhanced effector function. Notably, B. coccoides or acetate potentiated anti-PD-1 therapy in mouse melanoma models, supporting their potential as adjunctive strategies for melanoma immunotherapy. Conclusions: These findings support a model of an acetate-TLR3-linked PI3K/Akt signaling axis linking microbiota-associated metabolites to CD8 ⁺ T cell-mediated antitumor immunity. Importantly, our study highlights both B. coccoides and its derivative, acetate, as preclinical adjunctive candidates to potentiate anti-PD-1 efficacy in melanoma.

Atopic dermatitis (AD) is linked to gut microbiota dysbiosis, yet the mechanisms connecting specific commensals to cutaneous immunoregulation remain elusive. We observed reduced Bifidobacterium breve ( B. breve ) abundance in AD patients. A new B. breve strain was isolated from human stools and nomenclated as Yang08 . In MC903‐induced AD‐like mouse models, Yang08 outperformed a standard strain, ameliorating disease severity, including reduced ear thickening, epidermal hyperplasia, and mast cell infiltration in a manner dependent on viable bacteria and an intact gut microbiota. Antibiotic‐mediated microbiota depletion abrogated its efficacy, while fecal microbiota transfer from Yang08 ‐treated mice conferred protection, confirming microbial remodeling as essential. Metagenomics revealed Yang08 specifically enriched Akkermansia muciniphila , which was required for therapeutic effects in germ‐free mice. Mechanistically, Yang08 abolished both neutrophil influx and NET deposition in lesions, with ex vivo experiments showing blunted NETosis capacity. Its therapeutic benefits were reversed by neutrophil depletion, NET degradation, or PAD4 inhibition. Overall, Yang08 alleviates AD by enriching A. muciniphila and inhibiting skin NETosis, emerging as a promising prophylactic candidate prevention for AD prevention.

Growing evidence demonstrates that the immunoregulatory properties of vitamin D are primarily mediated by its active hormonal form, 1,25-dihydroxyvitamin D3 (calcitriol). This secosteroid modulates immune homeostasis through three principal mechanisms: (1) strengthening antimicrobial defense via innate immune potentiation, (2) downregulating pathological inflammatory cascades, and (3) fine-tuning adaptive immunity through lymphocyte differentiation control. Clinically, serum concentrations of the inactive precursor, 25-hydroxyvitamin D3 (25(OH)D3), exhibit an inverse correlation with systemic immune activation and the prevalence/severity of dermatological conditions, including atopic dermatitis, psoriasis, and systemic sclerosis. Suboptimal 25(OH)D3 levels are thus recognized as a modifiable risk factor for such disorders, with vitamin D3 supplementation demonstrating therapeutic potential in improving clinical outcomes. Furthermore, prolonged vitamin D3 supplementation may reduce disease incidence across a spectrum of dermatopathologies. This review synthesizes contemporary mechanistic and clinical insights into vitamin D’s immunoregulatory role in cutaneous diseases. To optimize therapeutic efficacy, future clinical trials should incorporate analysis of vitamin D receptor (VDR) polymorphisms as a predictive biomarker in vitamin D3 intervention strategies.

Objective: Bifidobacterium is known to be depleted in patients with atopic dermatitis (AD). This study aims to investigate the potential prophylactic effects of Bifidobacterium animalis subsp. lactis BX-BC08 (B. lactis BX-BC08) in a murine model of AD. Design: The immunosuppressive and anti-inflammatory effects of BX-BC08 were evaluated in a MC903-induced AD mouse model. Gut microbiota composition was analyzed by metagenomic sequencing, while high-performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to identify anti-inflammatory molecules produced by B. lactis BX-BC08. Results: BX-BC08 significantly attenuated pro-inflammatory responses, scaling and swelling in the MC903-induced AD like murine model compared to controls. Fecal microbial profiling revealed an enrichment of probiotics and a reduction of pro-inflammatory bacteria in BX-BC08 treated mice. Metabolic analysis of BX-BC08 bacteria culture supernatant and treated mice identified a significant enrichment of alpha-Ketoglutaric acid (AKG). Functional validation in the murine AD model demonstrated that AKG strongly suppressed T helper 2 (Th2)-driven pro-inflammatory responses. Conclusion: BX-BC08 mitigates AD-like inflammation by producing the anti-inflammatory metabolite AKG. BX-BC08 could serve as a novel prophylactic agent for AD prevention.