Journal of microbiology and biotechnology最新文献

Neuroinflammation, an immune process in the central nervous system (CNS), is a key contributor to a range of neurological diseases, including neurodegenerative disorders (e.g., Alzheimer's and Parkinson's disease), stroke, and depression, underscoring its significant pathological relevance. While maackiain (MAA) exhibits potent anti-inflammatory activity, its potential to mitigate neuroinflammation remains poorly understood. This study investigated the therapeutic effects of MAA on lipopolysaccharide (LPS)-induced neuroinflammation and its underlying mechanisms. In vitro, MAA significantly improved BV2 cell viability and reduced nitric oxide (NO) expression in LPS-treated cells, decreased the expression of reactive oxygen species (ROS), and it also inhibited the accumulation of Ferrous ion (Fe²⁺) and lipid peroxides as well as the damage to mitochondria. Higher concentrations of MAA were more effective, consistent with subsequent animal experiments. In vivo, mice treated with MAA showed improved memory in the Morris water maze compared to the LPS group. Nissl staining revealed fewer IBA-1 positive cells and a decrease in COX-2 and IL-6 levels in the hippocampus and cortex. This compound also increased the number of normal neurons in the cortex and CA3 region. The results of this study highlight the inhibitory effects of MAA on neuroinflammation, suggesting its potential as an effective therapeutic agent for treating neuroinflammation.

Recurrent respiratory tract infections (RRTIs) are a major cause of morbidity in children, and strain-defined probiotics have been proposed as a supportive preventive strategy, although clinical evidence remains limited. In this randomized, double-blind, placebo-controlled trial, 120 children diagnosed with RRTIs received either Bifidobacterium animalis subsp. lactis XLTG11 and Lactiplantibacillus plantarum CCFM8661 or a matched placebo daily for 180 days. The probiotic group demonstrated significantly reduced duration and frequency of fever, cough, upper respiratory tract infections, trachea/bronchitis, pneumonia, and overall RRTI recurrence compared with the placebo group (all p < 0.05). Gut microbiota profiling showed clear community differences between groups at day 180, with the probiotic group exhibiting greater abundance of beneficial commensal taxa and the placebo group showing higher representation of opportunistic genera. Functional pathway analysis indicated shifts consistent with enhanced metabolic stability in probiotic recipients. Immune biomarker patterns further supported a more regulated humoral response in the probiotic group, reflected by comparatively stable IgG, IgM, and complement C3 levels over the intervention period. Growth trajectories remained normal in both groups, and no treatment-related adverse events were reported, confirming a favorable safety profile. These findings indicate that long-term supplementation with XLTG11 and CCFM8661 is safe, well tolerated, and effective in reducing RRTI burden in children, while also supporting healthier microbiota and immune patterns. This trial provides evidence for the use of strain-defined probiotics as a complementary approach within pediatric respiratory infection prevention strategies.

The gut microbiome plays a fundamental role in host metabolism, immune regulation, and disease development. With the rapid accumulation of multi-omics and literature data, the microbiome field now faces the challenge of efficiently extracting scientific insights from massive, heterogeneous datasets. Artificial intelligence (AI) and large language models (LLMs) provide promising tools to address this complexity by enabling integrative analysis and knowledge synthesis across diverse biological sources. In this study, we developed METABOLISM, a microbiome-specialized LLM fine-tuned on 160,000 scientific abstracts to enhance literature-based contextual understanding of microbiome-liver interactions and related biological mechanisms. Using LoRA-based parameter-efficient training, METABOLISM was optimized for domain-specific reasoning and response generation. Model performance was evaluated through both automated Phi-4 scoring (a large language model-based evaluator for relevance, informativeness, and fluency) and structured human expert rubric assessments involving 20 domain specialists. The fine-tuned METABOLISM achieved superior relevance and clarity scores (mean > 7.5 ± 0.06) compared with general-purpose LLMs such as Gemma-3-12B-IT and ChatGPT-4o. Correlation analysis revealed weak to moderate negative relationships (R = -0.65, p < 0.0001) between traditional NLP metrics (BLEU, ROUGE) and human expert rubric scores, with a similar trend observed for correlations with Phi-4-based automated evaluation scores, indicating the limitations of surface-level similarity measures in biomedical contexts. Overall, our findings demonstrate that microbiome-adapted LLMs can effectively distill high-volume scientific data into biologically meaningful insights, supporting more efficient and interpretable research in microbiology and systems biology.

Atopic dermatitis (AD) is a chronic inflammatory skin condition influenced by immune dysregulation. This study aimed to evaluate the effects of a mineral-postbiotic (Lactobacillus plantarum VIOAP03 and Lactobacillus fermentum VIMPP04) mixture to alleviate AD symptoms in the NC/Nga mouse model. AD was induced in NC/Nga mice using HDM ointment throughout experiment. After inducing AD skin lesions, mice were orally administered ED mineral powder, postbiotics, and a mixture of ED mineral powder and postbiotics. Key parameters measured included dermatitis score, transepidermal water loss (TEWL), and scratching behavior. To assess the effects, serum analyses (IgE, histamine, IgG1, IgG2a) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to quantify Th1/Th2 cytokine responses in dorsal skin tissues. Histological analyses (Hematoxylin & Eosin, Toluidine Blue staining) were performed to assess the dermal thickness and the count of mast cells in the dorsal skin tissues. The mixture group exhibited the most significant improvements in dermatitis score, TEWL, and reduced scratching behavior. Histological analyses showed a decrease in mast cells, along with reduced epidermal thickness, in the mixture group compared to the negative control group. Through the mixture group serum analyses and qRT-PCR, inflammatory markers were downregulated compared to the negative control group, while Th1/Th2 cytokine balance shifted towards reduced Th2 dominance. The combined administration of mineral-postbiotics mixture showed synergistic effects in alleviating AD symptoms by modulating Th1/Th2 cytokine responses. These findings highlight the potential of this combination as a novel therapeutic approach for managing atopic dermatitis.

Listeria monocytogenes is a deadly foodborne pathogen, its virulence factors Listeriolysin O (LLO) and Sortase A (SrtA) play a critical role in its infection and have been identified as key targets for developing its inhibitor. This study reveals that the natural compound Dryocrassin ABBA (ABBA) alleviates the toxicity of L. monocytogenes by effectively inhibiting the functions of LLO and SrtA. ABBA bound to the binding pocket of LLO and inhibited the formation of its oligomers, which in turn reduced the ability of LLO to lyse mammalian erythrocytes. When co-cultured with L. monocytogenes, ABBA reduced the hemolytic activity of the cultural supernatant. In addition, ABBA bound to SrtA and reduced its transpeptide activity, which in turn resulted in a reduction in the formation of bacterial biofilm, the adhesion and invasion of L. monocytogenes to cells. Thr415 and Lys505 of LLO, and Asn92 and Pro220 of SrtA are critical residues on promoting their binding with ABBA by forming non-covalent weak interactions. ABBA reduced the cytotoxicity and inflammatory responses mediated by L. monocytogenes, and demonstrated protective effect against L.monocytogenes-infected Galleria mellonella. ABBA did not show anti-L. monocytogenes properties and cytotoxicity effect under the test concentrations, promising its potential to be developed as an anti-L. monocytogenes infection agent.

This study aimed to evaluate the antidepressant-like effects of Gami-Soyosan (GSS) in a corticosterone-induced mouse model of depression. Behavioral assessments, including the forced swim test and tail suspension test, demonstrated that GSS significantly reduced immobility, indicating improved coping behaviors comparable to those of fluoxetine. Serum analysis revealed that GSS lowered pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, indicating an attenuation of systemic inflammatory cytokine responses in this model. Metabolomic profiling further showed that GSS modulated amino acid and nitrogen-related pathways, including branched-chain amino acids, arginine, and histidine/β-alanine metabolism, supporting the restoration of metabolic homeostasis under stress. Distinct metabolic signatures were also observed when compared to fluoxetine, indicating that GSS may exert antidepressant-like effects through partially different mechanisms. In addition, in vitro experiments using neuronal cells demonstrated that GSS attenuated oxidative stress by reducing whole-cell ROS generation and enhancing lysosomal activity, highlighting a neuroprotective role. Together, these findings provide multi-layered evidence that GSS acts through behavioral, immune, metabolic, and oxidative pathways, supporting its potential as a complementary therapeutic approach for stress-related depression.

Ensuring the safety of microbial strains intended for probiotic use is essential, particularly for species such as Escherichia coli (E. coli), which include both commensal and pathogenic lineages. E. coli 5C is a recently identified polyketide synthase (pks)-negative strain isolated from healthy infant feces and characterized as free of virulence factors, plasmids, and antimicrobial resistance, suggesting suitability as a probiotic. To confirm its in vivo safety, we evaluated the subacute oral toxicity of E. coli 5C in immunocompetent and immunocompromised rodent models. A GLP-compliant 28-day repeated-dose oral toxicity study was conducted in Wistar rats following OECD Test Guideline 407 (2008 edition), complemented by a parallel non-GLP study in athymic nude mice to assess safety under impaired immune function. Animals received purified water (control) or E. coli 5C at 500, 1000, or 2000 mg/kg/day (~0.5, 1, or 2 × 10¹¹ CFU/kg/day), as low, mid, and high dose, respectively, daily for 28 days. Clinical signs, behaviour, body weight, feed intake, functional observations, haematology, biochemistry, urinalysis, organ weights, gross necropsy, and histopathology were evaluated. Across all treated groups in both species, E. coli 5C produced no mortality, morbidity, or adverse clinical effects. Haematological, biochemical, and behavioural parameters remained comparable to controls, and organ weights, gross pathology, and microscopic examinations revealed no test item-related abnormalities. No systemic infection was observed. No treatment-related adverse effects were observed at any dose level, and the highest tested dose of 2,000 mg/kg/day (2 × 10¹¹ CFU/kg/day) was therefore identified as the No Observed Adverse Effect Level (NOAEL). These findings demonstrate the absence of subacute toxicity of E. coli 5C in both normal and immunodeficient hosts and provide a favourable preclinical safety foundation for its continued development as a candidate probiotic strain.

As the aging population grows, the proportion of postmenopausal women is also increasing. Menopause can cause various symptoms and reduce quality of life. Hormone replacement therapy (HRT) is a common treatment to alleviate these symptoms, but long-term use carries the risk of side effects such as breast cancer and endometriosis, highlighting the need for new alternatives. Astragalus sinicus is a plant native to East Asia, primarily used to improve rice cultivation in paddies. However, research on its potential as a medicinal resource remains limited. Therefore, this study aimed to evaluate the potential of A. sinicus ethanol extract as a treatment for menopause-related symptoms using the MCF-7 breast cancer cell line and ovariectomized (OVX) mice. In vitro experiments confirmed that A. sinicus ethanol extract improved the mRNA expression of menopause-related genes and exhibited estrogenic activity. Additionally, in vivo experiments demonstrated that A. sinicus ethanol extract effectively alleviated menopausal symptoms. These findings suggest that A. sinicus ethanol extract may serve as a novel alternative for addressing menopause-related health issues.

Osteoarthritis (OA) is a common cause of chronic pain and functional impairment in older adults. Evidence suggests a gut-joint axis, where gut dysbiosis and systemic low-grade inflammation may contribute to OA pathogenesis. Postbiotics, which are non-viable microbial products such as heat-killed bacteria, have been proposed as safe and stable alternatives to live probiotics. ID-CBT5101, a tyndallized Clostridium butyricum preparation, reduced inflammation and preserved cartilage in a rat OA model. We conducted a 12-week randomized, double-blind, placebo-controlled trial to assess ID-CBT5101 safety and efficacy in adults with mild-to-moderate knee OA. Ninety-six participants were randomized to receive either ID-CBT5101 (1.0 × 10¹⁰ CFU-equivalents/day) or placebo. The primary endpoint was the change from baseline in walking pain on a 100-mm visual analog scale (VAS). Secondary outcomes included WOMAC, Korean Knee Score (KKS), patient global assessment, and serum biomarkers. Both groups showed significant within-group improvements in VAS, WOMAC, and KKS over 12 weeks. However, no significant differences were observed between groups for any clinical endpoint. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), prostaglandin E₂ (PGE₂), leukotriene B₄ (LTB₄), transforming growth factor-β (TGF-β), and high-sensitivity C-reactive protein (hs-CRP) showed no consistent changes favoring ID-CBT5101. Safety profiles were comparable between groups, with no treatment-related adverse events. ID-CBT5101 was safe and well-tolerated, but it did not demonstrate significant clinical efficacy compared with placebo.

Astragalus polysaccharide (APS) has recently emerged as a potent antitumor agent, however its impact on breast cancer (BC) remains inadequately understood. The current research aimed to examine the regulatory mechanism of APS in the pathogenesis of BC examining its influence on N6-methyladenosine (m⁶A) modification of MAL2. The effect of APS on the malignant phenotypes of BC was assessed by CCK8, EdU, transwell and tumor xenograft model assays. The differentially expressed genes (DEGs) in BC were identified by GEPIA-BC database, and their expression levels were determined by qRT-PCR in the BC cells. The role of MAL2 in BC malignancy was examined by EdU and transwell assays. Furthermore, bioinformatics analysis was first employed to explore the m⁶A modification site of MAL2 mediated by METTL3, which was then validated through MeRIP, western blotting, and qRT-PCR assays. APS was found to significantly reduce the cell proliferation, migration, as well as invasion of MCF-7 (IC50: 1014 μg/ml) and MDA-MB-231 (IC50: 685 μg/ml) cell lines. Additionally, it effectively suppressed tumor growth in vivo. The bioinformatics analysis revealed that among the five DEGs, MAL2 was significantly downregulated upon APS treatment both BC cell lines. Furthermore, the overexpression of MAL2 partially reversed the anti-tumor effects of APS. Notably, METTL3 modulates the m⁶A modification of MAL2 to regulate tumorigenesis in BC. APS prevents BC progression in association with reduced METTL3 expression and altered m⁶A modification of MAL2, suggesting that MAL2 may represent a potential therapeutic target to enhance the efficacy of APS.