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Immunophyletic relationships between actinomycetales and eubacteriales determined by examinations of their cytoplasmic antigens.

Cytoplasms obtained from a total of 205 different strains of Actinomycetales, Eubacteriales, Lower Fungi, and Protozoa were examined against selected anti-cytoplasm antisera using the immunodiffusion and counterimmunoelectrophoresis procedures. Immunological relationships between the different genera have been revealed and, in respect to Eubacteriales, the possible immunophyletic determinants have been discerned. Cytoplasms of Enterobacter, Clostridium, Staphylococcus, and Diplococcus were found to retain the significant linkage determinants between large groups of Eubacteriales and Actinomycetales. Evolutionary implications of the findings are discussed.

Actinomycetales

Immunochemical analysis of soluble antigens of Mycobacterium lepraemurium.

Soluble antigens obtained from purified M. lepraemurium were identified by SDS polyacrylamide gel electrophoresis as three different proteins, M-W 1 X 10(4), 1 X 10(5), and 4 X 10(6), and two polysaccharide-polypeptides. Three antigens were found to react with anti-M. leprae antiserum; a single antigen proved to be immunologically related to M. tuberculosis, M. similae, M. balnei and a few other mycobacteria, but not to Eubacteriales and fungi, as examined by immunoelectrophoresis. In the dermal hypersensitivity assay, the guinea pigs sensitized with soluble antigens of M. lepraemurium only responded to the antigens of M. lepraemurium, M. leprae and partly to M. scrofulaceum, but not to other antigens, including lepromin and leprous serum globulins.

Actinomycetales

Oral Lachnoanaerobaculum Levels and Survival in Patients With Head and Neck Cancer.

IMPORTANCE: The oral microbiome plays a critical role in cancer treatment responses, yet its influence on outcomes in patients with head and neck squamous cell carcinoma (HNSCC) undergoing (chemo)radiotherapy remains poorly understood. Identifying specific microbiome signatures associated with treatment effectiveness could provide novel prognostic biomarkers and therapeutic targets. OBJECTIVE: To investigate the association between salivary Lachnoanaerobaculum spp abundance and treatment outcomes in patients with HNSCC undergoing (chemo)radiotherapy and to explore potential mechanisms. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study analyzed saliva samples from patients with HNSCC who were enrolled in 2 independent prospective biomarker studies (SALIVA and ZissTrans) and underwent definitive (chemo)radiotherapy. Oral microbiome composition was assessed using 16S rRNA gene sequencing. Tumor-infiltrating lymphocytes (TILs) were evaluated via immunohistochemistry in patients with available data. Findings were further assessed using data from The Cancer Microbiome Atlas and The Cancer Genome Atlas. Sample collection occurred from 2008 to 2011 (SALIVA) and from 2017 to 2022 (ZissTrans), and the data for this study were analyzed from July to December 2024. EXPOSURE: Definitive (chemo)radiotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was locoregional recurrence-free survival (LRFS) and a secondary outcome was overall survival (OS). Additional secondary analyses evaluated the association between Lachnoanaerobaculum spp levels and TIL levels, and the incidence of severe radiation-induced oral mucositis. RESULTS: The analysis included 92 patients with HNSCC (mean [SD] age, 61.1 [7.9] years; 15 female [16.3%] 77 male [83.7%] individuals) and found that higher Lachnoanaerobaculum spp abundance was associated with substantially improved LRFS (median, 69 vs 11 months; hazard ratio [HR], 0.50; 95% CI, 0.29-0.86) and OS (median, 75 vs 27 months; HR, 0.54; 95% CI, 0.30-0.98). This finding was confirmed by multivariable Cox regression (LRFS: HR, 0.50; 95% CI, 0.25-1.00; OS: HR, 0.37; 95% CI, 0.16-0.85). TILs were evaluated in 76 patients (82.2%) and showed that increased Lachnoanaerobaculum spp levels were associated with higher CD4-positive and CD8-positive TIL counts. Lachnoanaerobaculum spp abundance showed no meaningful association with severe radiation-induced oral mucositis. Data from The Cancer Microbiome Atlas (n = 157) indicated that higher intratumoral Lachnoanaerobaculum spp levels were associated with improved OS (HR, 0.62; 95% CI, 0.39-0.98). Transcriptomic analyses in The Cancer Genome Atlas cohort further supported an immune-stimulated tumor microenvironment in Lachnoanaerobaculum-high tumors. CONCLUSIONS AND RELEVANCE: This prognostic study found that higher salivary Lachnoanaerobaculum spp abundance was associated with improved tumor control and survival in patients with HNSCC undergoing (chemo)radiotherapy. These findings support further investigation into microbiome-targeted interventions to improve HNSCC treatment effectiveness.

Humans

Mitsuokella apri sp. nov., a novel species of the family Selenomonadaceae isolated from faeces of a wild boar (Sus scrofa).

A Gram-stain-negative, rod-shaped, obligately anaerobic strain, designated WILCCON 0060T, was isolated from the faecal sample of a wild boar (Sus scrofa) collected on the Island of Ubin (Pulau Ubin), Singapore (1.4126°N, 103.9577°E). Phylogenetic and comparative analyses based on 16S rRNA gene and whole-genome sequences indicated that strain WILCCON 0060T belongs to the genus Mitsuokella, within the family Selenomonadaceae. Notably, the average nucleotide identity and digital DNA-DNA hybridization values between strain WILCCON 0060T and the type strains of two existing Mitsuokella species, Mitsuokella multacida DSM 20544T and Mitsuokella jalaludinii DSM 13811T, only ranged from 84.6-84.9% and 24.1-24.7%, respectively, both well below the recommended species delineation thresholds of 95.0% and 70.0%. Supported by additional physiological, biochemical and genomic differences, these findings collectively indicate that strain WILCCON 0060T represents a novel species within the genus Mitsuokella. We propose the species name Mitsuokella apri sp. nov., pertaining the isolation of the type strain WILCCON 0060T (= DSM 120052T = LMG 33761T) from a faecal sample of a wild boar.

Animals

Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.

Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.

Crohn Disease

Capsaicin ameliorates glycemic levels via gut microbiota-derived 5-aminolevulinic acid in mice.

BACKGROUND: Capsaicin, a natural alkaloid in chili peppers, regulates glycemic levels; however, its mechanisms and therapeutic potential remain unclear. This study aimed to elucidate the role of gut microbiota and their metabolites in mediating capsaicin's glycemic regulatory effects. We conducted experiments in specific pathogen-free (SPF) and germ-free (GF) mice, transient receptor potential vanilloid 1 (TRPV1) receptor ablation studies, and fecal microbiota transplantation (FMT) to demonstrate the involvement of gut microbiota in capsaicin-mediated glycemic control. Metagenomics and metabolomics analyses were employed to identify key microbial strains and metabolic pathways. Keystone strains and metabolites were supplemented in GF mice without capsaicin intervention to validate their effects on glycemic regulation. In vitro co-culture experiments were performed to investigate the mutualistic relationships among keystone strains under capsaicin treatment. RESULTS: Gut microbiota constitute an important component of capsaicin-mediated glycemic regulation, acting in concert with but not solely dependent on TRPV1 signaling. Gut microbiota altered by capsaicin promote the production of 5-aminolevulinic acid (5-ALA), which contributes to heme synthesis and enhances glycemic control. Supplementation with Akkermansia muciniphila, Ligilactobacillus murinus, or 5-ALA in GF mice recapitulates the glycemic benefits of capsaicin. Furthermore, capsaicin enriches Akkermansia muciniphila, which in turn supports the growth of Ligilactobacillus murinus. CONCLUSION: Capsaicin-induced changes in the gut microbiota promote 5-ALA synthesis, leading to improved glycemic control. These findings suggest that dietary or probiotic interventions targeting gut microbiota, particularly Akkermansia muciniphila and 5-ALA, may offer promising strategies for managing glycemic disorders, including type 2 diabetes (T2D). Video Abstract.

Animals