Frontiers in Microbiology最新文献

Background: Helicobacter pylori (H. pylori) is a class I carcinogen that induces gastric cancer (GC). The mechanisms underlying its induction of GC are not fully understood. The role of the MSTRG.10627.1/miR-142-5p/ADAMTS5 pathway induced by H. pylori in GC was investigated in this study.

Methods: RNA sequencing and bioinformatics analysis were used to screen a regulatory pathway lncRNA-miRNA-mRNA. The dual luciferase reporter was used to evaluate interactions between the lncRNA and the miRNA or between the miRNA and the mRNA. The cellular biological effects of ADAMTS5 were detected using clonogenic formation and cell migration assays. A western blot was used to assess the protein expression of the pathway. The role of ADAMTS5 in tumor growth and metastasis was validated in nude mice using subcutaneous and tail vein injections.

Results: A regulatory axis lncRNA (MSTRG.10627.1)-miRNA (miR-142-5p)-mRNA (ADAMTS5) with the highest correlation coefficient was screened out. The combinations between MSTRG.10627.1 and miR-142-5p or between miR-142-5p and ADAMTS5 were verified. The expression of ADAMTS5 was down-regulated by H. pylori (p < 0.05). The proliferation, migration, and invasion of GC cells were increased by down-regulation of ADAMTS5 (p < 0.05); however, the proliferation, migration, and invasion of GC cells were inhibited by the overexpression of ADAMTS5 (p < 0.05). After silencing of ADAMTS5 in GC cell lines, western blot showed that the expression of PI3K protein and the phosphorylation level of AKT protein were increased (p < 0.05), and the expression of tumor suppressor p53 was inhibited (p < 0.05). However, overexpression of ADAMTS5 in GC cells induced the opposite results (p < 0.05). The results of the subcutaneous tumor model in nude mice showed that tumor weight and volume increased after silencing of ADAMTS5 (p < 0.05). The metastasis of GC cells in the metastatic tumor model was inhibited by overexpression of ADAMTS5 (p < 0.05).

Conclusion: The expression of ADAMTS5 was down-regulated by H. pylori through regulating a probable pathway (MSTRG.10627.1-miR-142-5p-ADAMTS5). Moreover, down-regulated ADAMTS5 induced PI3K protein, up-regulated phosphorylated AKT protein, and down-regulated p53, which plays an important role in the induction of GC.

Background: Dysmenorrhea is a prevalent gynecological disorder with multifactorial pathophysiology, including prostaglandin overproduction, inflammation, and pain sensitization. Emerging evidence suggests that gut microbiota may contribute to pain modulation, although causal relationships remain unclear.

Methods: Bidirectional two-sample Mendelian randomization (MR) was performed to investigate causal associations between dysmenorrhea and gut microbiota. Complementary in vivo validation was conducted in a primary dysmenorrhea (PDM) rat model treated with ibuprofen or the traditional Chinese medicine Wenjing Zhitong Decoction (WJZTD). The gut microbiota composition was analyzed using 16S rRNA sequencing, and correlations with pain-related parameters were assessed.

Results: Forward MR analyses revealed that genetic liability to dysmenorrhea influenced the abundance of specific gut taxa, notably reducing Lachnospiraceae genera and increasing Erysipelotrichaceae, which was consistent with observed alterations in PDM rats. Reverse MR provided no robust evidence that gut microbiota causally affect dysmenorrhea. In the PDM model, both ibuprofen and WJZTD produced analgesic effects, but induced distinct microbial signatures: ibuprofen increased the presence of Staphylococcus, while WJZTD enriched the population of Bifidobacterium. Correlation analyses highlighted Blautia as a microbiota feature associated with reduced pain, suggesting that modulation of this genus may represent a potential therapeutic strategy.

Conclusion: This study demonstrates that dysmenorrhea causally alters gut microbiota composition. The restoration of Blautia and Bifidobacterium by WJZTD is associated with pain alleviation, highlighting gut microbiota modulation as a potential strategy for dysmenorrhea management.

Background: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.

Objective: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.

Methods: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 h later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1-, and 3-days post-injury (dpi) included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.

Results: TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume at 3 dpi. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.

Conclusion: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.

Coastal ecosystems in Hainan exhibit steep sea-land gradients in salinity and nutrient availability, yet the rhizosphere microbiome of the pioneer shrub Heliotropium arboreum remains poorly understood. We investigated bacterial and fungal communities across seven coastal sites using replicated transects from seaward to shrub-belt to inland zones, and linked community patterns to soil physicochemical properties and human disturbance. Bacterial communities consistently showed higher richness, evenness, and compositional stability than fungal communities. Alpha diversity increased from seaward to inland zones for both groups, with a stronger gradient in fungi. Community composition was dominated by Proteobacteria and Planctomycetota in bacteria and Ascomycota in fungi, with distinct dominant genera across zones and sites. β-diversity analyses revealed clear differentiation of microbial communities among zones and locations, with fungi showing stronger turnover and site separation than bacteria, indicating higher sensitivity to environmental filtering and disturbance. Redundancy analysis indicated that fungal communities were primarily structured by available potassium, total nitrogen, and soil organic carbon, whereas bacterial communities were most strongly associated with soil pH (7.468-9.613 across sites) and nitrate concentrations. Functional profiling suggested complementary roles in decomposition and nitrogen cycling, and human-disturbed sites showed higher predicted pathogenic potential. Overall, H. arboreum hosts an environmentally filtered rhizosphere microbiome shaped jointly by coastal gradients and disturbance, with fungi responding more strongly than bacteria to spatial and environmental variation.

Background: Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy worldwide. Gut microbiota play crucial roles in liver disease progression and may offer noninvasive diagnostic value, yet microbial signatures specific to advanced HCC remain unclear.

Methods: Seventy-six participants, including early-stage HCC (HCC12), advanced HCC (HCC34), liver cirrhosis (LC), and healthy controls (CG), were prospectively enrolled. Fecal samples underwent 16S rRNA sequencing to characterize microbial diversity and community composition. Differential taxa were identified using Kruskal-Wallis tests, linear discriminant analysis effect size (LEfSe), and zero-inflated negative binomial regression (ZINB). Machine learning models were constructed using clinical features, representative microbiota, and their combination. External validation was performed using 74 published HCC cases.

Results: Advanced HCC exhibited reduced microbial richness and diversity, accompanied by substantial community structure alterations. Enterococcus, Enterococcaceae, Enterobacteriaceae, and Escherichia-Shigella were enriched in HCC34, whereas Ruminococcus and Blautia were depleted. These taxa correlated strongly with liver injury markers and HCC-specific biomarkers. The extreme gradient boosting model showed high diagnostic potential when using either clinical or microbial features alone, while the combined model achieved improved accuracy (AUC = 1.0 in the primary test set). External validation supported the good generalizability of the model (AUC = 1.0 in the external cohort). Feature importance analysis identified Enterococcus as the most influential discriminator of advanced HCC.

Conclusion: This study reveals distinct gut microbial signatures associated with advanced HCC and suggests that Enterococcus may serve as a potentially important microbial marker linked to disease severity. Integrating gut microbiota profiling with clinical features may offer a promising noninvasive strategy for the accurate identification of advanced HCC and provides hypothesis-generating insights for microbiome-based therapeutic interventions.

Background: Dysbiotic oral biofilms produce virulence factors, such as lipopolysaccharide (LPS), triggering and sustaining chronic inflammation in periodontal tissues. Modulation of the bioactivity of these products offers a potential novel, adjunctive approach beyond conventional periodontal therapy.

Methods: Pooled saliva and subgingival biofilm samples from 324 healthy, gingivitis, and periodontitis participants were assessed for endotoxin activity using the recombinant Factor C (rFC) assay. Functional immune-stimulation was evaluated in THP-1 and THP-1 Dual cell models through NF-κB and IRF pathways activation assessment and cytokine profiling. The modulatory effects of antimicrobial peptide LL-37 and the LPS-binding compound Polymyxin B on saliva and subgingival biofilm inflammatory potential were assessed in the same models.

Results: Recombinant Factor C assays demonstrated marked reductions in endotoxin activity of saliva and subgingival biofilms treated with LL-37 and Polymyxin B (>90% reduction). Both NF-κB and IRF signaling were broadly attenuated following modulation, with polymyxin B exerting greater suppression of NF-κB activity, while LL-37 showed stronger inhibition of IRF, particularly in salivary samples. Pro-inflammatory cytokines secretion by THP-1 cells (IL-1β, IL-6, IL-8, and TNF-α) challenged with bio-modulated samples decreased by 40-75% compared to untreated samples. Interestingly, anti-inflammatory cytokines such as TGF-β and IL-10 remained largely unchanged, suggesting selective suppression of the cytokine cascade.

Conclusion: Modulating LPS-associated virulence activity substantially reduces the inflammatory potential of saliva and subgingival plaque. LL-37 and Polymyxin B illustrate complementary strategies for LPS modulations and highlight the feasibility of their use as adjunctive approaches for the prevention and treatment of periodontal diseases.

The review organizes current knowledge on the biofunctions, life-history strategies, and environmental responses of Chloroflexota in agricultural soils. Members of this phylum play key roles in carbon, nitrogen, and phosphorus cycling through a high degree of metabolic versatility, including photosynthesis, redox reactions, and the degradation of complex organic compounds such as cellulose and lignin. Chloroflexota contribute to major soil processes, including nitrification, denitrification, and nitrogen fixation. In agricultural soils, the predominant classes are Anaerolineae and Ktedonobacteria, each exhibiting distinct ecological strategies. Anaerolineae members, such as Leptolinea, Bellilinea, and Anaerolinea, are often associated with nutrient-enriched conditions, suggesting copiotrophic or competitor- and ruderal-like traits. In contrast, Ktedonobacteria show negative responses to increased soil carbon and nitrogen, suggesting that its members are oligotrophic. Despite these trends, responses to soil organic carbon, nitrogen, phosphorus, and pH vary substantially across studies, likely due to functional heterogeneity within the phylum and insufficient taxonomic resolution in metataxonomic datasets. Emerging evidence from metagenome-assembled genomes (MAGs) reveals that Chloroflexota harbor genes involved in carbon fixation, nitrogen transformations, and phosphorus solubilization, highlighting their previously underestimated ecological significance. However, most Chloroflexota remain uncultured, and available genomic data are still limited. Future research integrating high-resolution taxonomic profiling, metagenomics, and cultivation-based approaches is needed to clarify the ecological roles and life-history strategies of Chloroflexota members. Such advances may ultimately establish this phylum as an important microbial indicator of soil fertility and environmental change in agricultural soils.

Background: Clostridioides difficile infection (CDI) poses a major clinical challenge in patients with inflammatory bowel disease (IBD) due to overlapping symptoms, diagnostic complexities, and distinct therapeutic considerations. The interaction between CDI and IBD involves disrupted gut microbiota, immune dysregulation, and disease-specific risk factors.

Methods: This review critically examines the current evidence on the diagnosis and management of CDI in patients with IBD. Literature sources discussing diagnostic methodologies, therapeutic strategies, and preventive interventions were analyzed, with a focus on recent advances and their clinical applicability.

Results: Diagnosing CDI in IBD remains difficult due to similar clinical presentations between infectious colitis and IBD flares, alongside limitations of stool assays, molecular tests, and endoscopic evaluations. Emerging diagnostic tools may enhance the accuracy and timeliness of detection. Standard therapies, antibiotics, and fecal microbiota transplantation (FMT) remain essential; however, their application requires individualization, taking into account immunosuppressive therapy, drug interactions, and the risk of recurrence. Treatment outcomes are further influenced by disease severity and patterns of antimicrobial resistance. Preventive strategies, including antimicrobial stewardship, probiotics, and vaccination, may help reduce the incidence of CDI among patients with IBD.

Conclusion: CDI in IBD necessitates a personalized management approach that incorporates accurate diagnostics, targeted therapy, and preventive measures. Despite therapeutic advances, significant knowledge gaps persist regarding host microbiome interactions and the optimization of individualized treatment. Future research should focus on improving diagnostic precision and developing personalized medicine strategies to enhance outcomes for IBD patients affected by CDI.