Suzi Zhang, Yuyu Zhang, Yi Luo, Silan Zhang, Yinjuan Song, Bin Li, Fuying Zheng, Pengchen Gao, Jian Xu, Yuefeng Chu
{"title":"Prevalence of N6-Methyladenosine (m6A) in Mycoplasma mRNA:Epitranscriptomic Regulation in Minimal Genomes.","authors":"Suzi Zhang, Yuyu Zhang, Yi Luo, Silan Zhang, Yinjuan Song, Bin Li, Fuying Zheng, Pengchen Gao, Jian Xu, Yuefeng Chu","doi":"10.1016/j.micpath.2025.108127","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.108127","url":null,"abstract":"<p><p>Messenger RNA N6 methyladenosine (m6A) modification has been considered as the main post-transcriptional modification of eukaryotic mRNA; however, its role in the regulation of prokaryotic mRNA transcription remains unclear. The N6 methyladenosine (m6A) modifications in prokaryotic mRNA has been found in Pseudomonas aeruginosa and Escherichia coli so far. In this study, ultra-high-pressure liquid chromatography coupled with triple quadrupole tandem mass spectroscopy (UHPLC-QQQ-MS/MS) was used to calculate the m6A/A ratio in multiple mRNA from a wide range of mycoplasma species, representing as a category of genomically minimal prokaryote. The results showed that mycoplasma mRNA has a higher m6A/A ratio than other prokaryotes and eukaryotes reported previously, varying in the range of 0.07-4.56%. Furthermore, Nano UMI meRIP-seq analysis (a high-resolution long-read sequencing approach integrating unique molecular identifiers (UMIs) to map RNA methylation at the transcriptome level across eight different mycoplasma species. It showed that most m6A peaks are located in the protein coding region with unique \"GGAGG\" motif, which is different from those described in eukaryotes and other prokaryotes previously. Gene Ontology (GO) analysis showed that the genes regulated by this methylation modification system was involved in the ribosome, pyrimidine metabolism, purine metabolism, pyruvate metabolism and other metabolic pathways required for mycoplasma growth. To explore the potential functional impact of m<sup>6</sup>A methylation, we performed RNA pull-down assays and identified three virulent candidate m<sup>6</sup>A-binding proteins: Tuf (elongation factor Tu), prfA (peptide chain release factor A), and mgtA (magnesium transporter A). Microscale thermophoresis (MST) analysis also revealed that the three proteins exhibited significantly stronger binding affinities to m<sup>6</sup>A-modified RNA compared to their unmethylated counterparts, demonstrating their selective recognition of methylated transcripts. Further structural prediction using AlphaFold3 suggested specific amino acid residues mediating interactions with methylated adenines, offering mechanistic insights into m<sup>6</sup>A-protein interactions. Together, these findings firstly provided the landscape of m<sup>6</sup>A RNA methylation in mycoplasma and suggest that m<sup>6</sup>A may participate in post-transcriptional regulation by modulating RNA-protein interactions in mycoplasma genome, hinting that epitranscriptomic m<sup>6</sup>A regulation of mycoplasma mRNA may be associated with pathogenicity.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108127"},"PeriodicalIF":3.5,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiao Wang , Qibin Jiang , Songmao Wu , Wei Fan , Kun Peng , Keyu Zhou , Lu Xu , Defang Chen , Xiaoli Huang , ping Ouyang , Yi Geng
{"title":"A review: Bacterial hemolysin-mediated iron dysregulation and immune cell damage synergistically drive ferroptosis","authors":"Jiao Wang , Qibin Jiang , Songmao Wu , Wei Fan , Kun Peng , Keyu Zhou , Lu Xu , Defang Chen , Xiaoli Huang , ping Ouyang , Yi Geng","doi":"10.1016/j.micpath.2025.108130","DOIUrl":"10.1016/j.micpath.2025.108130","url":null,"abstract":"<div><div>Hemolysin, a critical virulence factor of bacterial pathogens that disrupts host cell membranes, induces cytolysis and facilitates immune evasion during its infection. Ferroptosis, an iron-dependent form of regulated cell death (RCD), is characterized by the lethal accumulation of lipid peroxides and has emerged as a critical mechanism increasingly implicated in infectious pathogenesis. Iron is essential for cellular metabolism but becomes pathogenic when dysregulated; its redox activity catalyzes Fenton reactions within the iron-catalyzed Haber-Weiss cycle, generating reactive oxygen species (ROS) that propagate lipid peroxidation, a hallmark of ferroptosis. Hemolysins lyse erythrocytes, releasing hemoglobin-bound iron into iron overload. Crucially, these hemolysins also directly damage immune cells. The combined effects of iron overload and direct cytotoxicity culminate in immune cell ferroptosis, impairing host defenses and facilitating bacterial survival. This review synthesizes current knowledge on how pathogenic bacteria's hemolysin-mediated iron dysregulation and immune cell damage converge to induce ferroptosis in infection, underscoring its role in the pathogenesis. We also explore therapeutic strategies targeting hemolysins, iron chelation, and ferroptosis inhibition to mitigate disease severity and counter immune evasion.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108130"},"PeriodicalIF":3.5,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterisation of phage vB_Ec_DUEC01: A lytic Kagunavirus for multidrug-resistant Escherichia coli","authors":"Mahmoud E. Khalifa , Soad M. Omar","doi":"10.1016/j.micpath.2025.108124","DOIUrl":"10.1016/j.micpath.2025.108124","url":null,"abstract":"<div><div>Multi-drug resistant (MDR) <em>Escherichia coli</em> has become one of the significant global health concerns, and this demands the development of alternative strategies for antimicrobials. The present study describes the isolation and characterisation of bacteriophage vB_Ec_DUEC01- a virulent member of the class <em>Caudoviricetes</em>-which could serve as a potential biocontrol agent against MDR <em>E. coli</em>. Electron microscopy showed an icosahedral capsid and a long, non-contractile tail. The one-step growth curve resulted in a latent period of 20 min with a high burst size of 97 PFU per infected cell. Moreover, the phage showed reasonable stability over a pH range of 3.0–12.0 and at moderate temperatures of 20 °C–40 °C. Whole-genome sequencing revealed a genome of 43,949 bp encoding 77 open-reading frames (ORFs), encoding structural, packaging, DNA replication and metabolism, and lysis proteins. No lysogeny-related, antibiotic resistance, or virulence factor genes were found. Phylogenetic analysis placed the phage in the <em>Kagunavirus</em> genus, with closely related therapeutically relevant phages. Results suggest that vB_Ec_DUEC01 is effective, genetically safe, and stable; therefore, it is a preliminary good candidate for application as a biocontrol agent against MDR <em>E. coli</em>. Further, host-range and in vivo efficacy studies are necessary to develop this application in antimicrobial therapy.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108124"},"PeriodicalIF":3.5,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingfei Sun , Wenju Hu , Shiying Li , Md Ahsanul Kabir , Felix Kwame Amevor , Yingjie Wang , Weiwei Jin
{"title":"Berberine inhibits Mycoplasma synoviae infection by suppressing PIK3CA-dependent inflammatory and apoptotic responses in avian macrophages","authors":"Yingfei Sun , Wenju Hu , Shiying Li , Md Ahsanul Kabir , Felix Kwame Amevor , Yingjie Wang , Weiwei Jin","doi":"10.1016/j.micpath.2025.108114","DOIUrl":"10.1016/j.micpath.2025.108114","url":null,"abstract":"<div><div><em>Mycoplasma synoviae</em> (MS) is a widespread avian pathogen that causes respiratory disease and infectious synovitis in poultry, resulting in substantial economic losses. Current control measures are undermined by rising antimicrobial resistance and variable vaccine protection in certain settings, highlighting the need for alternative therapeutic strategies. Berberine (BBR), a natural isoquinoline alkaloid with established antibacterial and immunomodulatory activities, has not been previously investigated in the context of avian mycoplasmosis. Here, we evaluated the therapeutic potential of BBR against MS infection in avian HD11 macrophages. Treatment with BBR at its minimum inhibitory concentration (50 μg/mL) significantly suppressed MS growth and reduced bacterial adhesion to host cells. In parallel, BBR markedly attenuated the MS-induced upregulation of pro-inflammatory cytokines (TNF-α and IL-1β) and decreased apoptosis, as evidenced by reduced caspase-3 and increased Bcl-2 expression. Network pharmacology and molecular docking analyses identified phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), the catalytic subunit of PI3K, as a potential molecular target of BBR. Functional validation showed that BBR inhibited the PI3K/Akt signaling axis during infection. Moreover, PIK3CA knockdown recapitulated, whereas its overexpression reversed, the anti-inflammatory and anti-apoptotic effects of BBR. Together, these findings demonstrate that BBR exerts both direct antimicrobial activity and host-directed protective effects against MS infection by targeting PIK3CA-dependent signaling. This study provides mechanistic insight into the therapeutic action of BBR and supports its potential as a novel candidate for the control of MS in poultry.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108114"},"PeriodicalIF":3.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyan Wu , Xingyu Chen , Chenglong Yang , Zipeng Lin , Wenxiao Ma , Jianzheng Wang , Rong Huang , Fan Zhang
{"title":"Proteomic analysis of the response of Beauveria bassiana to HY60, an antifungal peptide from Pseudomonas aeruginosa of Blattella germanica","authors":"Xiaoyan Wu , Xingyu Chen , Chenglong Yang , Zipeng Lin , Wenxiao Ma , Jianzheng Wang , Rong Huang , Fan Zhang","doi":"10.1016/j.micpath.2025.108122","DOIUrl":"10.1016/j.micpath.2025.108122","url":null,"abstract":"<div><div>The antibacterial peptide HY60, isolated and purified from the gut bacterium <em>Pseudomonas aeruginosa</em> BGf-2 of <em>Blattella germanica</em>, can significantly inhibit the growth and reproduction of <em>Beauveria bassiana</em> in previous experiments, but the specific mechanism remains unclear. This study aimed to investigate the antimicrobial mechanism of HY60 against <em>B. bassiana</em>. First, both BGf-2 suspension and HY60 demonstrated significant suppression of <em>B. bassiana</em> proliferation. Electron microscopy further showed HY60-induced morphological aberrations including surface flocculation and vacuolization. Label-Free analysis was first used to reveal that HY60 affects key processes such as protein synthesis, oxidative stress response, energy metabolism, and cell wall biosynthesis. Western blot validation confirmed the HY60 downregulated the expression of AATM and GFAT1, consistent with proteomic results. These findings preliminarily reveal the mechanism of antimicrobial peptide HY60 against <em>B. bassiana</em>, providing valuable candidate targets for future development of innovative biocontrol strategies. Additionally, this study offers insights into the development of <em>B. germanica</em> biopesticides and lays a foundation for the research and development of mycotic drugs for beneficial economic insects.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108122"},"PeriodicalIF":3.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the bioactive potential of rhizospheric Streptomyces clavuligerus against Macrophomina phaseolina, an incitant of groundnut dry root rot disease","authors":"Parameshwari PalaniArul , Angappan Kathithachalam , Karthikeyan Muthusamy , Harish Sankarasubramanian , Anandham Rangasamy , Manikanda Boopathi Narayanan , Jayakanthan Mannu , Murugan Marimuthu","doi":"10.1016/j.micpath.2025.108093","DOIUrl":"10.1016/j.micpath.2025.108093","url":null,"abstract":"<div><div>Dry root rot caused by <em>Macrophomina phaseolina</em> is the most destructive soil-borne fungal disease that severely hampers groundnut production. This study investigated the multifaceted biocontrol and plant growth-promoting potential of rhizospheric <em>Streptomyces</em> spp., focusing on the strain <em>Streptomyces clavuligerus</em> GRS-8. <em>In vitro</em> dual culture assays revealed that GRS-8 exhibited the highest antifungal activity, inhibiting 76.50 % of <em>M. phaseolina</em> mycelial growth. The strain also produced key metabolites, including indole-3-acetic acid, siderophores, and hydrolytic enzymes, contributing to plant growth promotion and defense priming. In silico molecular docking identified quininone oxime as a potent bioactive compound with high binding affinity to five virulence-associated proteins of <em>M. phaseolina</em>. Molecular dynamics simulations confirmed the structural stability of the lipase–quininone oxime complex, supporting its potential as a fungal inhibitor. Under protected cultivation, the combined application of GRS-8 liquid formulation via seed treatment, basal application, and soil drenching significantly reduced dry root rot incidence by 73.10 % and enhanced the activity of host defense enzymes. These findings highlight the dualistic mechanism of <em>S. clavuligerus</em> GRS-8 involving direct antifungal action and host defense induction, underscoring its potential as a promising biocontrol agent for sustainable groundnut cultivation.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108093"},"PeriodicalIF":3.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luyang Zhou , Aofei Wang , Fahui Song , Jikun Wu , Changxu Yu , Shuqi Wei , Shuo Yang , Ruihua Zhang , Shijin Jiang , Yanli Zhu
{"title":"Development of droplet digital PCR (ddPCR) for the detection and quantification of Mycoplasma gallisepticum in duck flocks","authors":"Luyang Zhou , Aofei Wang , Fahui Song , Jikun Wu , Changxu Yu , Shuqi Wei , Shuo Yang , Ruihua Zhang , Shijin Jiang , Yanli Zhu","doi":"10.1016/j.micpath.2025.108123","DOIUrl":"10.1016/j.micpath.2025.108123","url":null,"abstract":"<div><div><em>Mycoplasma gallisepticum</em> (MG) is capable of infecting a variety of poultry species, leading to chronic respiratory diseases and posing a significant threat to the poultry industry's development. Although MG infections in chickens have been extensively studied, epidemiological data on ducks remain limited and often underestimated. To address this gap, we developed and validated a ddPCR-based method for the identification and quantification of MG in ducks, using the <em>mgc2</em> gene sequence. The method's sensitivity, specificity, and reproducibility were evaluated, and clinical samples were tested. The results indicated that the optimal reaction efficiency of the ddPCR was achieved with a primer concentration of 200 nM, a probe concentration of 100 nM, and an annealing temperature of 58.5 °C, resulting in the clearest demarcation between positive and negative droplets. This method has high specificity, with no cross-reactivity observed with other pathogens achieving a minimum detection limit of 10<sup>0</sup> copies/μL, and increasing tenfold more sensitive than quantitative PCR (qPCR). The coefficient of variation in repeatability tests was below 5 %. Furthermore, analysis of clinical samples revealed that the positive detection rate of ddPCR (53.3 %, 32/60) surpassed that of qPCR (46.7 %, 28/60). This ddPCR method serves as a useful tool for the early diagnosis of MG and assessment of epidemic situation.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108123"},"PeriodicalIF":3.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Muñiz-Bernal , Ana L. Ríos-López , Rogelio de J. Treviño-Rangel, Miguel A. Becerril-García, Ángel A. Torres, Orlando Flores-Maldonado
{"title":"Tannic acid exhibits therapeutic effects against azole-resistant invasive candidiasis and enhances the antifungal activity of fluconazole","authors":"Valeria Muñiz-Bernal , Ana L. Ríos-López , Rogelio de J. Treviño-Rangel, Miguel A. Becerril-García, Ángel A. Torres, Orlando Flores-Maldonado","doi":"10.1016/j.micpath.2025.108121","DOIUrl":"10.1016/j.micpath.2025.108121","url":null,"abstract":"<div><div><em>Candida albicans</em> is a priority threat to global health due to the emergence of strains resistant to antifungal drugs, such as azoles, and their high mortality rates, especially in hospital settings. Therefore, the search for new therapeutic strategies is crucial. Tannic acid is a phenolic compound that has shown potential antifungal activity against <em>Candida</em> species <em>in vitro</em>. This study evaluated the therapeutic effects of tannic acid alone and in combination with fluconazole in a murine model of invasive candidiasis. BALB/c mice were intravenously injected with either fluconazole-susceptible or -resistant <em>Candida albicans</em>, and then received the experimental treatments intraperitoneally for 3 days. Therapeutic efficacy was evaluated by determining animal survival, as well as fungal burden, tissue invasion and cytokine levels in the spleen, brain and kidney. Tannic acid increased the survival of mice with invasive candidiasis; Furthermore, treatment with tannic acid reduced fungal burden, tissue invasion and proinflammatory cytokine levels in disseminated organs during invasive candidiasis. Combination therapy of tannic acid plus fluconazole demonstrated a greater antifungal effect compared with monotherapy of both drugs during azole-resistant invasive candidiasis. These findings demonstrate the therapeutic efficacy of tannic acid against azole-resistant <em>Candida albicans</em>, representing a promising potential option for the adjuvant treatment of candidiasis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108121"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunsai He , Lu Ding , Chenxi Zhu , Jiacheng Yang , Taoyun Chen , Lan Lan , Ni Qing , Chanqing Yu , Bin Zhang
{"title":"Development and immunogenicity evaluation of bivalent virus-like particles against bovine nebovirus and bovine norovirus in mice","authors":"Chunsai He , Lu Ding , Chenxi Zhu , Jiacheng Yang , Taoyun Chen , Lan Lan , Ni Qing , Chanqing Yu , Bin Zhang","doi":"10.1016/j.micpath.2025.108118","DOIUrl":"10.1016/j.micpath.2025.108118","url":null,"abstract":"<div><div>Bovine Nebovirus (BNeV) and Bovine Norovirus (BNoV) are major causes of viral diarrhea in calves, leading to significant economic losses. Currently, no commercial vaccines exist for these pathogens. Here, we developed bivalent virus-like particles (VLPs) co-expressing BNeV and BNoV VP1 proteins using a baculovirus-insect cell system and evaluated their immunogenicity in mice. Both monovalent (BNoV or BNeV VLPs) and bivalent VLPs induced peak IgG titers by day 14 post-booster, with the bivalent VLPs triggering faster antibody production. Histo-blood group antigen (HBGA) blocking assays (BT50) showed that bivalent VLPs induced higher blocking antibody titers, peaking at day 14 and remaining elevated at day 28. Additionally, bivalent VLPs enhanced IFN-γ secretion and increased CD3<sup>+</sup>CD8<sup>+</sup> T-cell proportions. These findings demonstrate that BNeV-BNoV-VP1 bivalent VLPs effectively stimulate cellular immunity and blocking antibodies, supporting their potential as vaccines against BNeV and BNoV.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108118"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modulating metabolism and reproductive health through microbiome driven gut-brain axis therapies","authors":"Sammra Maqsood , Muhammad Asif , Sadaf Shakoor , Ayesha Saddiqa","doi":"10.1016/j.micpath.2025.108113","DOIUrl":"10.1016/j.micpath.2025.108113","url":null,"abstract":"<div><div>The gut microbiome plays a crucial role in regulating metabolic and reproductive health through the gut-brain axis. This review underscores the therapeutic potential of modulating gut microbiota to alleviate conditions such as obesity and polycystic ovarian syndrome (PCOS). Gut dysbiosis as an imbalance microbiome, has direct effect on insulin resistance, hormonal imbalances, and systemic inflammation. It contributes to metabolic and reproductive disparities. This study reveals the coordination between dysbiosis and obesity, and PCOS. Alterations in gut-microbiota is the major contributor of insulin-resistance, menstrual dysfunction, and hormonal imbalances. It also focuses on the efficacy of probiotic and relevant microbes. Considering the literature, microbiome-potential and its role in treating the interventions is significantly important. Outcomes recommend that gut-dysbiosis aggravates metabolic and reproductive health illnesses by making worse hormonal inequalities and inflammation. The therapy probiotic has indicated favorable outcomes in enhancing insulin-resistance and menstrual cycle regulation, highlighting its capability as a reliable treatment for PCOS and obesity. Nevertheless, well-monitored clinical trials are necessary on large scale to make it optimized microbiome-focused treatments for long-term results and safety.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108113"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}