Pub Date : 2025-09-24DOI: 10.1016/j.micres.2025.128349
Lingling Zhao , Hengqi He , Zhaohui Luo , Liwen Jin , Bo Xiao
Gut microbiota intricately regulate host cells through diverse mechanisms, with numerous pathways involving protein post-translational modifications (PTMs). This review comprehensively summarizes the impacts of the gut microbiota on various PTMs in host cells. It elaborates on how these modifications contribute to the development of host diseases, delving into mediating pathways, including changes in microbial metabolites, key enzymes, and the microenvironment. Conversely, it also explores how PTMs influence gut microbiota abundance. To overcome current research limitations, such as narrow perspectives and monotonous methods, novel strategies are proposed. Applying single-cell/spatial omics could reveal cell-type-specific and spatial PTM responses to microbial signals, while integrating AI algorithms with traditional experiments may predict PTM regulatory networks using microbial and host data. These strategies aim to expand research approaches and promote the clinical translation of findings in this field.
{"title":"Advances in the interaction between gut microbiota and post-translational modifications of proteins","authors":"Lingling Zhao , Hengqi He , Zhaohui Luo , Liwen Jin , Bo Xiao","doi":"10.1016/j.micres.2025.128349","DOIUrl":"10.1016/j.micres.2025.128349","url":null,"abstract":"<div><div>Gut microbiota intricately regulate host cells through diverse mechanisms, with numerous pathways involving protein post-translational modifications (PTMs). This review comprehensively summarizes the impacts of the gut microbiota on various PTMs in host cells. It elaborates on how these modifications contribute to the development of host diseases, delving into mediating pathways, including changes in microbial metabolites, key enzymes, and the microenvironment. Conversely, it also explores how PTMs influence gut microbiota abundance. To overcome current research limitations, such as narrow perspectives and monotonous methods, novel strategies are proposed. Applying single-cell/spatial omics could reveal cell-type-specific and spatial PTM responses to microbial signals, while integrating AI algorithms with traditional experiments may predict PTM regulatory networks using microbial and host data. These strategies aim to expand research approaches and promote the clinical translation of findings in this field.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128349"},"PeriodicalIF":6.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.micres.2025.128350
Xuan-wei Chen , Xiao-lin Zhang , Zhi-han Wang , Jia-yao Wu , Si-qi Tian , Zi-long Huang , Bo Peng
Streptococcus agalactiae (GBS) is a major pathogen causing severe infections in human and economic loss in animal farming, where β-lactams remain first-line therapy. However, emerging β-lactam resistance, including WHO-priority penicillin-resistant strains, threatens clinical efficacy, creating an urgent need for resistance-breaking adjuvants. In this study, we demonstrate that DL-Propargylglycine (PAG), an inhibitor of cystathionine-γ-lyase inhibitor, exclusively synergizes with β-lactams to reverse resistance in ampicillin-resistant GBS (AR-GBS) and other streptococci, overcoming tolerance in persisters and biofilms. Mechanistically, PAG potentiates antibiotic lethality through dual pathways: metabolic activation via enhanced central carbon metabolism for ROS production and cell envelope remodeling via concurrent downregulation of peptidoglycan biosynthesis genes and upregulation of capsular polysaccharide synthesis. This disrupts cell wall architecture, increases membrane permeability and accelerates antibiotic influx. While in vivo therapeutic efficacy in zebrafish was limited, PAG represents an adjuvant that overcomes β-lactam resistance through metabolic and membrane remodeling, paving the way for optimized derivatives.
{"title":"DL-propargylglycine reverses beta-lactam resistance in Streptococcus agalactiae","authors":"Xuan-wei Chen , Xiao-lin Zhang , Zhi-han Wang , Jia-yao Wu , Si-qi Tian , Zi-long Huang , Bo Peng","doi":"10.1016/j.micres.2025.128350","DOIUrl":"10.1016/j.micres.2025.128350","url":null,"abstract":"<div><div><em>Streptococcus agalactiae</em> (GBS) is a major pathogen causing severe infections in human and economic loss in animal farming, where β-lactams remain first-line therapy. However, emerging β-lactam resistance, including WHO-priority penicillin-resistant strains, threatens clinical efficacy, creating an urgent need for resistance-breaking adjuvants. In this study, we demonstrate that DL-Propargylglycine (PAG), an inhibitor of cystathionine-γ-lyase inhibitor, exclusively synergizes with β-lactams to reverse resistance in ampicillin-resistant GBS (AR-GBS) and other streptococci, overcoming tolerance in persisters and biofilms. Mechanistically, PAG potentiates antibiotic lethality through dual pathways: metabolic activation via enhanced central carbon metabolism for ROS production and cell envelope remodeling via concurrent downregulation of peptidoglycan biosynthesis genes and upregulation of capsular polysaccharide synthesis. This disrupts cell wall architecture, increases membrane permeability and accelerates antibiotic influx. While <em>in vivo</em> therapeutic efficacy in zebrafish was limited, PAG represents an adjuvant that overcomes β-lactam resistance through metabolic and membrane remodeling, paving the way for optimized derivatives.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128350"},"PeriodicalIF":6.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.micres.2025.128351
Zihe Zhou , Mengzhe Li , Hanyu Fu , Zhongyu Han , Zhenchao Wu , Huahao Fan , Ning Shen , Jiajia Zheng
The escalating threat of antimicrobial resistance underscores the urgent need for innovative therapeutic strategies. Phage therapy has experienced a resurgence over the past five years following a prolonged period of neglect during the antibiotic era. Despite its therapeutic promise, critical barriers impede clinical translation, including susceptibility to interference from the host's complex physiological environment, a narrow host range, and the inability to lyse intracellular bacteria. To address these limitations and optimize the efficacy of phage-mediated treatment, recent research has increasingly focused on biomaterial-assisted approaches aimed at enhancing therapeutic efficacy. In this review, we concentrate on recent progress in biomaterial-assisted phage-based treatment strategies, including phage physical encapsulation strategies and phage surface chemical coupling strategies. Physical encapsulation employs liposomes, hydrogels, pH-sensitive polymers and etc. for controlled phage delivery, while surface chemical coupling modifies phage capsids with photosensitizers, nanozymes, or metal nanoparticles to enable multifunctional bactericidal mechanisms. In addition, accessibility for phage therapy of intracellular bacteria is discussed. We also conclude key biomaterial selection criteria-prioritizing biosafety, biodegradability, and microenvironment adaptability, and offer novel perspectives for advancing therapeutic precision as well as multidimensional innovation in combating antimicrobial resistance.
{"title":"Biomaterial-driven innovations in phage therapy: Current strategies and future perspectives","authors":"Zihe Zhou , Mengzhe Li , Hanyu Fu , Zhongyu Han , Zhenchao Wu , Huahao Fan , Ning Shen , Jiajia Zheng","doi":"10.1016/j.micres.2025.128351","DOIUrl":"10.1016/j.micres.2025.128351","url":null,"abstract":"<div><div>The escalating threat of antimicrobial resistance underscores the urgent need for innovative therapeutic strategies. Phage therapy has experienced a resurgence over the past five years following a prolonged period of neglect during the antibiotic era. Despite its therapeutic promise, critical barriers impede clinical translation, including susceptibility to interference from the host's complex physiological environment, a narrow host range, and the inability to lyse intracellular bacteria. To address these limitations and optimize the efficacy of phage-mediated treatment, recent research has increasingly focused on biomaterial-assisted approaches aimed at enhancing therapeutic efficacy. In this review, we concentrate on recent progress in biomaterial-assisted phage-based treatment strategies, including phage physical encapsulation strategies and phage surface chemical coupling strategies. Physical encapsulation employs liposomes, hydrogels, pH-sensitive polymers and etc. for controlled phage delivery, while surface chemical coupling modifies phage capsids with photosensitizers, nanozymes, or metal nanoparticles to enable multifunctional bactericidal mechanisms. In addition, accessibility for phage therapy of intracellular bacteria is discussed. We also conclude key biomaterial selection criteria-prioritizing biosafety, biodegradability, and microenvironment adaptability, and offer novel perspectives for advancing therapeutic precision as well as multidimensional innovation in combating antimicrobial resistance.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128351"},"PeriodicalIF":6.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radiation-induced bone loss remains clinically challenging due to limitations of existing treatments. Using a mouse model of fractionated total abdominal irradiation (TAI), we demonstrate that TAI triggers severe osteoporosis characterized by trabecular bone loss, suppressed osteogenesis, and elevated osteoclast activity. Through 16S rRNA sequencing and immune profiling, we found TAI induced gut dysbiosis, immune dysregulation such as Th17/Treg imbalance, and systemic inflammation. Oral supplementation with C. butyricum reversed bone loss, activated osteogenic signaling, suppressed osteoclastogenesis, and rebalanced T-cell subsets in mice. Crucially, it restored gut microbiota composition and attenuated inflammation in intestinal and bone marrow microenvironments. Our findings establish C. butyricum as a gut microbiota-targeted therapy for radiation-induced bone loss via the gut-immune-bone axis.
{"title":"Clostridium butyricum attenuates radiation-induced bone loss through gut microbiota and immune regulation in mice","authors":"Jinmin Lv , Hao Chen , Yichao Ni , Yue Zhang , Xingrui Huang","doi":"10.1016/j.micres.2025.128352","DOIUrl":"10.1016/j.micres.2025.128352","url":null,"abstract":"<div><div>Radiation-induced bone loss remains clinically challenging due to limitations of existing treatments. Using a mouse model of fractionated total abdominal irradiation (TAI), we demonstrate that TAI triggers severe osteoporosis characterized by trabecular bone loss, suppressed osteogenesis, and elevated osteoclast activity. Through 16S rRNA sequencing and immune profiling, we found TAI induced gut dysbiosis, immune dysregulation such as Th17/Treg imbalance, and systemic inflammation. Oral supplementation with <em>C. butyricum</em> reversed bone loss, activated osteogenic signaling, suppressed osteoclastogenesis, and rebalanced T-cell subsets in mice. Crucially, it restored gut microbiota composition and attenuated inflammation in intestinal and bone marrow microenvironments. Our findings establish <em>C. butyricum</em> as a gut microbiota-targeted therapy for radiation-induced bone loss via the gut-immune-bone axis.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128352"},"PeriodicalIF":6.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.micres.2025.128346
M.F. Lombardo , A. Abdelfattah , V. Catara , N. Wang , G. Cirvilleri
Citrus, a globally significant fruit crop, harbours a distinctive microbial community crucial for maintaining citrus health and enhancing disease resistance. While the structure and shaping factors, including phytosanitary treatments, of citrus root and leaf microbiomes are well documented, the carposphere (fruit surface) microbiome and its response to phytosanitary inputs remain poorly understood. In the present study, we combined culture independent (amplicon sequencing) and culture dependent techniques to analyse the citrus carposphere microbiome across three citrus hosts and its response to field-applied phytosanitary treatments (biologicals and copper-antimicrobials). Despite host-specific variation in the relative abundance of dominant taxa such as Proteobacteria, Firmicutes, and Basidiomycota, all three citrus hosts shared a core microbiome, consistently present across fruit samples. Bacterial diversity and composition were negatively influenced by copper treatments, whereas biological products (chitosan, sweet orange essential oils and their mixtures) had minimal or no negative impacts. Fungal communities, including potential pathogens, appeared less sensitive to treatments. Network analysis confirmed that copper altered microbial interactions, increasing mutual exclusion relationships between bacterial taxa compared to untreated or biologically treated samples, which were dominated by positive interactions. A parallel survey of cultivable microbiota from the same samples identified potential biocontrol agents (BCAs) against Colletotrichum gloeosporioides and Alternaria alternata. Notably, cross-referencing cultivable BCAs with core Amplicon Sequence Variants (ASVs) showed that 81.7 % of bacterial core members represent potential biocontrol agents. This study highlights the importance of management practices for sustaining beneficial microbiomes. Furthermore, it establishes a valuable resource of core-associated BCAs, offering promising avenues for the biological control of fungal pathogens.
{"title":"Citrus fruit microbiome changes under copper-based and biological alternative treatments and its biocontrol potential","authors":"M.F. Lombardo , A. Abdelfattah , V. Catara , N. Wang , G. Cirvilleri","doi":"10.1016/j.micres.2025.128346","DOIUrl":"10.1016/j.micres.2025.128346","url":null,"abstract":"<div><div>Citrus, a globally significant fruit crop, harbours a distinctive microbial community crucial for maintaining citrus health and enhancing disease resistance. While the structure and shaping factors, including phytosanitary treatments, of citrus root and leaf microbiomes are well documented, the carposphere (fruit surface) microbiome and its response to phytosanitary inputs remain poorly understood. In the present study, we combined culture independent (amplicon sequencing) and culture dependent techniques to analyse the citrus carposphere microbiome across three citrus hosts and its response to field-applied phytosanitary treatments (biologicals and copper-antimicrobials). Despite host-specific variation in the relative abundance of dominant taxa such as Proteobacteria, Firmicutes, and Basidiomycota, all three citrus hosts shared a core microbiome, consistently present across fruit samples. Bacterial diversity and composition were negatively influenced by copper treatments, whereas biological products (chitosan, sweet orange essential oils and their mixtures) had minimal or no negative impacts. Fungal communities, including potential pathogens, appeared less sensitive to treatments. Network analysis confirmed that copper altered microbial interactions, increasing mutual exclusion relationships between bacterial taxa compared to untreated or biologically treated samples, which were dominated by positive interactions. A parallel survey of cultivable microbiota from the same samples identified potential biocontrol agents (BCAs) against <em>Colletotrichum gloeosporioides</em> and <em>Alternaria alternata</em>. Notably, cross-referencing cultivable BCAs with core Amplicon Sequence Variants (ASVs) showed that 81.7 % of bacterial core members represent potential biocontrol agents. This study highlights the importance of management practices for sustaining beneficial microbiomes. Furthermore, it establishes a valuable resource of core-associated BCAs, offering promising avenues for the biological control of fungal pathogens.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128346"},"PeriodicalIF":6.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.micres.2025.128347
Xinyi Huo , Lianying Mao , Chenyu Dong, Wenguang Yang, Heng Zhang, Lei Zhang
Cyclic di-GMP (c-di-GMP) is a second messenger molecule that is widely distributed in bacteria and plays various physiologically important regulatory roles through interactions with a variety of effector molecules. Sigma (σ) factors are the predominant transcription factors involved in transcription regulation in bacteria. While c-di-GMP has been shown to bind to a range of transcription factors, c-di-GMP-binding σ factors have never been reported before. In a c-di-GMP/σ factors binding screen, we identified the σ factor RpoH as a c-di-GMP-responsive transcription factor in Pseudomonas aeruginosa PAO1. We further show that the binding of c-di-GMP to RpoH inhibits binding of RpoH to the promoters of its target genes such as asrA and dnaK, thereby downregulating the expression of these genes and reducing the resistance of P. aeruginosa to heat shock and aminoglycoside antibiotics. RpoH from Escherichia coli, Burkholderia thailandensis and Agrobacterium tumefaciens are also capable of binding c-di-GMP, suggesting that c-di-GMP-mediated control of the activity of RpoH is conserved in members of Proteobacteria.
{"title":"c-di-GMP regulates the resistance of Pseudomonas aeruginosa to heat shock and aminoglycoside antibiotics by targeting the σ factor RpoH","authors":"Xinyi Huo , Lianying Mao , Chenyu Dong, Wenguang Yang, Heng Zhang, Lei Zhang","doi":"10.1016/j.micres.2025.128347","DOIUrl":"10.1016/j.micres.2025.128347","url":null,"abstract":"<div><div>Cyclic di-GMP (c-di-GMP) is a second messenger molecule that is widely distributed in bacteria and plays various physiologically important regulatory roles through interactions with a variety of effector molecules. Sigma (σ) factors are the predominant transcription factors involved in transcription regulation in bacteria. While c-di-GMP has been shown to bind to a range of transcription factors, c-di-GMP-binding σ factors have never been reported before. In a c-di-GMP/σ factors binding screen, we identified the σ factor RpoH as a c-di-GMP-responsive transcription factor in <em>Pseudomonas aeruginosa</em> PAO1. We further show that the binding of c-di-GMP to RpoH inhibits binding of RpoH to the promoters of its target genes such as <em>asrA</em> and <em>dnaK</em>, thereby downregulating the expression of these genes and reducing the resistance of <em>P. aeruginosa</em> to heat shock and aminoglycoside antibiotics. RpoH from <em>Escherichia coli, Burkholderia thailandensis</em> and <em>Agrobacterium tumefaciens</em> are also capable of binding c-di-GMP, suggesting that c-di-GMP-mediated control of the activity of RpoH is conserved in members of Proteobacteria.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128347"},"PeriodicalIF":6.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 10.1016/j.micres.2025.128345
Antonio Marín-Castillo, Sergio León-Zaragoza, Alejandro Franco, Jero Vicente-Soler, Andrés Núñez, Teresa Soto, Marisa Madrid, José Cansado
Cytokinesis, the final step of cell division, must be precisely coordinated with the cellular metabolic status, yet the underlying regulatory mechanisms remain poorly understood. Here we show that in Schizosaccharomyces pombe, glucose signaling promotes cytokinesis via the evolutionarily conserved cAMP–PKA signaling pathway. Loss of the Pka1 catalytic subunit delays assembly and constriction of the contractile actomyosin ring (CAR), whereas constitutive PKA activation enhances CAR integrity and accelerates cytokinesis. Mechanistically, Pka1 downregulates the basal activity of the stress-activated MAPK Sty1 under glucose-rich conditions, thereby stabilizing the formin For3 and its nucleated actin cables, which collaborate to regulate CAR dynamics. Remarkably, cAMP–PKA signaling also facilitates cytokinesis through a parallel, actin cable–independent mechanism. Additionally, mitochondrial respiration contributes to cytokinesis in the presence of glucose through a PKA-independent pathway. These findings reveal a multilayered network that links carbon source metabolism to cytoskeletal organization and underscore the importance of tight PKA activity control for robust cell division.
{"title":"Metabolic control of cytokinesis by glucose cAMP–PKA signaling in fission yeast","authors":"Antonio Marín-Castillo, Sergio León-Zaragoza, Alejandro Franco, Jero Vicente-Soler, Andrés Núñez, Teresa Soto, Marisa Madrid, José Cansado","doi":"10.1016/j.micres.2025.128345","DOIUrl":"10.1016/j.micres.2025.128345","url":null,"abstract":"<div><div>Cytokinesis, the final step of cell division, must be precisely coordinated with the cellular metabolic status, yet the underlying regulatory mechanisms remain poorly understood. Here we show that in <em>Schizosaccharomyces pombe</em>, glucose signaling promotes cytokinesis via the evolutionarily conserved cAMP–PKA signaling pathway. Loss of the Pka1 catalytic subunit delays assembly and constriction of the contractile actomyosin ring (CAR), whereas constitutive PKA activation enhances CAR integrity and accelerates cytokinesis. Mechanistically, Pka1 downregulates the basal activity of the stress-activated MAPK Sty1 under glucose-rich conditions, thereby stabilizing the formin For3 and its nucleated actin cables, which collaborate to regulate CAR dynamics. Remarkably, cAMP–PKA signaling also facilitates cytokinesis through a parallel, actin cable–independent mechanism. Additionally, mitochondrial respiration contributes to cytokinesis in the presence of glucose through a PKA-independent pathway. These findings reveal a multilayered network that links carbon source metabolism to cytoskeletal organization and underscore the importance of tight PKA activity control for robust cell division.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128345"},"PeriodicalIF":6.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 10.1016/j.micres.2025.128343
Md. Mizanur Rahaman , Karma Yeshi , Mehedi Hasan Bappi , Md. Zohorul Islam , Phurpa Wangchuk , Subir Sarker
Inflammatory bowel disease (IBD) is a chronic, multifactorial disorder of the gastrointestinal tract, often associated with dysbiosis in gut microbiota. While the exact cause of IBD remains unclear, alterations in gut microbiome composition and function are recognised as key contributors to IBD pathogenesis. Natural compounds with anti-inflammatory properties are increasingly explored as potential therapeutic options for IBD. This study evaluated the therapeutic effects of two newly isolated galloyl glucosides—galloyl-lawsoniaside A (comp-4) and uromyrtoside (comp-6)—alongside dexamethasone (DEX) on microbiome regulation in a 2, 4, 6-Trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model. We employed PacBio HiFi full-length 16S rRNA gene sequencing on mouse colon tissue to assess changes in the intestinal microbiome and its associated functional pathways. TNBS-induced colitis significantly altered microbial composition, increasing the abundance of Acutalibacter muris, Monoglobus pectinilyticus, Streptococcus pneumoniae, Parabacteroides merdae, and Haemophilus influenzae, while decreasing Staphylococcus ureilyticus and Mailhella massiliensis. Treatment with comps 4 and 6 effectively restored the imbalanced microbiota. Functional pathway analysis revealed that colitis reduced microbial pathways, including peptidoglycan biosynthesis and the Bifidobacterium shunt. These disruptions were restored following treatment with our plant-derived compounds. Functional improvements were likely associated with reduced IL-6 production and restoring intestinal barrier integrity. Notably, comp-4 exhibited the most pronounced therapeutic efficacy across both microbial and host-associated parameters. In silico docking further supported the anti-inflammatory and immunomodulatory potential of these compounds. Together, our findings highlight the interplay between microbial function and host immunity in IBD and identify plant-derived galloyl glucosides as promising candidates for microbiome-targeted IBD therapeutics.
炎症性肠病（IBD）是一种慢性、多因素的胃肠道疾病，通常与肠道微生物群的生态失调有关。虽然IBD的确切病因尚不清楚，但肠道微生物组组成和功能的改变被认为是IBD发病的关键因素。具有抗炎特性的天然化合物越来越多地被探索作为IBD的潜在治疗选择。本研究在2,4,6 -三硝基苯磺酸（TNBS）诱导的小鼠结肠炎模型中，评估了两种新分离的没食子酰葡萄糖苷——没食子酰lawsoniside A （comp-4）和尿myrtoside （comp-6）与地塞米松（DEX）一起对微生物组的调节作用。我们对小鼠结肠组织采用PacBio HiFi全长度16S rRNA基因测序来评估肠道微生物组及其相关功能通路的变化。tnbs诱导的结肠炎显著改变了微生物组成，增加了死亡针状杆菌、果胶单胞杆菌、肺炎链球菌、merdae副杆菌和流感嗜血杆菌的丰度，同时减少了尿毒葡萄球菌和马塞勒麦氏杆菌的丰度。对照4和对照6有效地恢复了不平衡的菌群。功能通路分析显示，结肠炎减少了微生物通路，包括肽聚糖生物合成和双歧杆菌分流。用我们的植物源性化合物处理后，这些破坏得以恢复。功能改善可能与减少IL-6产生和恢复肠屏障完整性有关。值得注意的是，comp-4在微生物和宿主相关参数中都表现出最显著的治疗效果。硅对接进一步支持了这些化合物的抗炎和免疫调节潜力。总之，我们的研究结果强调了IBD中微生物功能和宿主免疫之间的相互作用，并确定了植物来源的没食子酰糖苷是微生物组靶向IBD治疗的有希望的候选者。
{"title":"Novel plant-derived compounds modulate gut microbiome dysbiosis in colitis mice: A potential therapeutic avenue for inflammatory bowel disease","authors":"Md. Mizanur Rahaman , Karma Yeshi , Mehedi Hasan Bappi , Md. Zohorul Islam , Phurpa Wangchuk , Subir Sarker","doi":"10.1016/j.micres.2025.128343","DOIUrl":"10.1016/j.micres.2025.128343","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic, multifactorial disorder of the gastrointestinal tract, often associated with dysbiosis in gut microbiota. While the exact cause of IBD remains unclear, alterations in gut microbiome composition and function are recognised as key contributors to IBD pathogenesis. Natural compounds with anti-inflammatory properties are increasingly explored as potential therapeutic options for IBD. This study evaluated the therapeutic effects of two newly isolated galloyl glucosides—galloyl-lawsoniaside A (comp-4) and uromyrtoside (comp-6)—alongside dexamethasone (DEX) on microbiome regulation in a 2, 4, 6-Trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model. We employed PacBio HiFi full-length 16S rRNA gene sequencing on mouse colon tissue to assess changes in the intestinal microbiome and its associated functional pathways. TNBS-induced colitis significantly altered microbial composition, increasing the abundance of <em>Acutalibacter muris</em>, <em>Monoglobus pectinilyticus</em>, <em>Streptococcus pneumoniae</em>, <em>Parabacteroides merdae</em>, and <em>Haemophilus influenzae</em>, while decreasing <em>Staphylococcus ureilyticus</em> and <em>Mailhella massiliensis</em>. Treatment with comps 4 and 6 effectively restored the imbalanced microbiota. Functional pathway analysis revealed that colitis reduced microbial pathways, including peptidoglycan biosynthesis and the Bifidobacterium shunt. These disruptions were restored following treatment with our plant-derived compounds. Functional improvements were likely associated with reduced IL-6 production and restoring intestinal barrier integrity. Notably, comp-4 exhibited the most pronounced therapeutic efficacy across both microbial and host-associated parameters. <em>In silico</em> docking further supported the anti-inflammatory and immunomodulatory potential of these compounds. Together, our findings highlight the interplay between microbial function and host immunity in IBD and identify plant-derived galloyl glucosides as promising candidates for microbiome-targeted IBD therapeutics.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"302 ","pages":"Article 128343"},"PeriodicalIF":6.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-14DOI: 10.1016/j.micres.2025.128342
Kaiyue Ding , Yuexue Huo , Kangzhe Fu , Yingting Chen , Lunyue Xia , Junhao Zhan , Jiahua Liu , Jiayu Liu , Yudi Liu , Mingyang Zhang , Xingchen Wu , HyokChol Choe , Danping Zhao , Junnan Ma , Chunmei Dai , Zhenlong Yu , Yulin Peng , Xiaochi Ma , Lin Zhang
Ovarian cancer (OC) is a highly lethal gynecologic malignancy characterized by limited availability of treatment options and frequent recurrence. The gut microbiota has emerged as a key regulator of tumor progression; however, the anticancer potential of individual probiotic species remains insufficiently characterized and warrants further investigation. Ferroptosis is a regulated iron-dependent cell death with therapeutic potential in cancer. In this study, we initially observed that the traditional herbal pair, Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Wild) R.J. Wang (SD) exerted antitumor effects in a mouse model of OC, which was accompanied by a marked increase in the abundance of Faecalibacterium prausnitzii (F.prausnitzii) — a beneficial commensal bacterium not previously associated with cancer or ferroptosis. This observation prompted us to explore the functional role of F.prausnitzii in OC and revealed that it significantly suppressed ovarian tumor growth both in vitro and in vivo. Mechanistically, F.prausnitzii treatment elevated Fe²⁺ levels, increased lipid peroxidation, and depleted glutathione (GSH), which are hallmarks of ferroptosis. Transcriptomic analysis of tumor tissues from F.prausnitzii-treated mice identified ferroptosis and metal ion homeostasis pathways as major regulatory networks. Furthermore, metabolomic profiling revealed the activation of phenylalanine metabolism and increased production of phenylacetylglutamine (PAGln), suggesting a microbiota-metabolite axis contributing to ferroptosis induction. Our findings reveal that F.prausnitzii represents a novel ferroptosis-inducing probiotic with potent antitumor activity in OC. This study reveals a previously unrecognized role for this gut commensal and provides a mechanistic basis for the development of microbiota-based, ferroptosis-targeted therapeutic strategies in oncology.
卵巢癌（OC）是一种高度致命的妇科恶性肿瘤，其特点是治疗选择有限，复发频繁。肠道微生物群已成为肿瘤进展的关键调节因子；然而，单个益生菌物种的抗癌潜力仍然不够充分，需要进一步研究。铁下垂是一种受调节的铁依赖性细胞死亡，具有治疗癌症的潜力。在这项研究中，我们最初观察到传统的草药对，黄芩（Scutellaria barbata D. Don， SB）和弥漫性白僵菌（scleroomitrion diffusum, Wild） R.J. Wang （SD）在OC小鼠模型中发挥抗肿瘤作用，同时伴随着Faecalibacterium prausnitzii （f.p prausnitzii）丰度的显著增加，Faecalibacterium prausnitzii是一种有益的共生细菌，以前与癌症或铁中毒无关。这一观察结果促使我们探索F.prausnitzii在卵巢癌中的功能作用，并发现其在体外和体内均能显著抑制卵巢肿瘤的生长。在机制上，F.prausnitzii处理升高了Fe 2 +水平，增加了脂质过氧化和谷胱甘肽（GSH）的消耗，这些都是铁死亡的标志。通过对prausnitzii治疗小鼠肿瘤组织的转录组学分析，发现铁凋亡和金属离子稳态通路是主要的调控网络。此外，代谢组学分析显示苯丙氨酸代谢的激活和苯乙酰谷氨酰胺（PAGln）的产生增加，表明微生物代谢轴有助于诱导铁下垂。我们的研究结果表明，F.prausnitzii是一种新的诱导铁中毒的益生菌，在OC中具有很强的抗肿瘤活性。这项研究揭示了这种肠道共生体以前未被认识到的作用，并为开发基于微生物群的肿瘤中以铁中毒为目标的治疗策略提供了机制基础。
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