mSystems最新文献

{"title":"Young gut microbiota transplantation improves the metabolic health of old mice.","authors":"Jiaojiao Xie, Taewan Kim, Zhongmao Liu, Hunter Panier, Suresh Bokoliya, Ming Xu, Yanjiao Zhou","doi":"10.1128/msystems.01601-24","DOIUrl":"https://doi.org/10.1128/msystems.01601-24","url":null,"abstract":"<p><p>The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.</p><p><strong>Importance: </strong>The gut microbiome is a key hallmark of aging. Fecal microbiota transplantation (FMT) using young microbiota represents a novel rejuvenation strategy to delay aging. Our study provides compelling evidence that transplanting microbiota from young mice significantly improved grip strength, frailty, and body composition in aged recipient mice. At the molecular level, FMT improved aging-related metabolic markers in the gut and circulation. Additionally, FMT from young microbiota rejuvenated the amygdala of the aged brain by downregulating inflammatory pathways. This study highlights the importance of metabolic reprogramming via young microbiota FMT in improving physical and metabolic health in elderly recipients.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0160124"},"PeriodicalIF":5.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical proteomics enhances the understanding of 2AA stress in <i>Salmonella enterica</i>.","authors":"Dominik Schum, Michaela K Fiedler, Wangchen Shen, Stephan A Sieber, Diana M Downs","doi":"10.1128/msystems.00540-25","DOIUrl":"https://doi.org/10.1128/msystems.00540-25","url":null,"abstract":"<p><p>Pyridoxal 5'-phosphate (PLP) is an essential cofactor for enzymes that catalyze diverse reactions in central metabolism. 2-Aminoacrylate (2AA) is a reactive enamine and an obligate catalytic intermediate in some PLP-mediated reactions. In the absence of the enamine/imine deaminase RidA, <i>Salmonella enterica</i> accumulates 2AA, which causes cellular stress. 2AA can attack PLP in the active site of some enzymes and covalently inactivate them by forming a 2AA-PLP adduct, which has already been characterized for some target enzymes <i>in vivo</i> and <i>in vitro</i>. The mechanism of 2AA attack suggests that a majority of cellular PLP-DEs would be targets of 2AA damage. Herein, a chemical proteomics workflow that uses PL (pyridoxal) probes to enrich PLP-DEs with a click chemistry-based protocol was implemented to investigate the global scale of 2AA damage in <i>S. enterica</i>. The results showed that PLP-DEs could be enriched in <i>S. enterica</i> with two different PL probes. When cells were labeled by providing a PL probe as the sole source of vitamin B6, several proteins were found to be more enriched when grown in conditions of high 2AA versus low 2AA stress. These data identified proteins that were previously shown to be attacked by 2AA as well as new candidate targets, demonstrating the usefulness of this approach to define the 2AA stress response with a global perspective. Growth analyses indicated that 2AA stress impacts the salvage of PL probes, suggesting that these and other PL probes will be valuable in future physiological studies to understand PLP salvage, a critical pathway in all organisms. In total, this study expands our understanding of 2AA metabolism and takes an initial step toward characterizing the global impact of 2AA stress in <i>S. enterica</i>.</p><p><strong>Importance: </strong>Loss of RidA homologs results in 2-aminoacrylate stress in <i>Salmonella</i> and other bacteria. The stress is derived from the reaction of 2AA with a pyridoxal phosphate cofactor in metabolic enzymes, which inactivates the respective enzymes. This study uses a chemical proteomic method and, with an initial test case, explores the damage that is generated by 2AA on a global proteomic scale. This work provides a basis for probing the extent of 2AA stress in different organisms and for identifying the enzymes targeted by 2AA.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0054025"},"PeriodicalIF":5.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Farewell and thanks for all the fish.","authors":"Jack A Gilbert","doi":"10.1128/msystems.00671-25","DOIUrl":"https://doi.org/10.1128/msystems.00671-25","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0067125"},"PeriodicalIF":5.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial dysbiosis and its diagnostic potential in androgenetic alopecia: insights from multi-kingdom sequencing and machine learning.","authors":"Xiaochen Wang, Fengjuan Li, Yangyang Sun, Fan Meng, Yaolin Song, Xiaoquan Su","doi":"10.1128/msystems.00548-25","DOIUrl":"https://doi.org/10.1128/msystems.00548-25","url":null,"abstract":"<p><p>Androgenetic alopecia (AGA), the most common form of hair loss, has been linked to dysbiosis of the scalp microbiome. In this study, we collected microbiome samples from the frontal baldness and occipital regions of patients with varying stages of AGA and conducted a comprehensive analysis of bacterial and fungal communities using 16S rRNA and ITS1 sequencing. Our results revealed that although the scalp microbiome dynamics in healthy subjects correlated strongly with chronological age, this trend was disrupted in AGA patients due to severe microbial imbalances, emphasizing the significant impact of AGA on the scalp microecology. Notably, microbial dysbiosis was not confined to the localized areas of hair loss but extended across the entire scalp. Moreover, the degree of dysbiosis was consistent with the severity of AGA. Leveraging multi-kingdom microbial features and machine learning, we developed a microbial index of scalp health (MiSCH), which effectively detects AGA and stratifies its severity. More importantly, MiSCH was able to identify high-risk individuals, those with significantly disrupted microbiome structures but no overt AGA phenotypic characteristics, thereby offering opportunities for early diagnosis, risk assessment, and personalized treatment of AGA.IMPORTANCEBy analyzing the bacteria and fungi on the scalp, this study shows how androgenetic alopecia (AGA) disrupts the balance of microbes not just in the hair loss areas, but across the entire scalp. Thus, we introduce the microbial index of scalp health (MiSCH), which leverages microbiome data for the early detection and severity prediction of AGA. This method is especially valuable for identifying people at risk of developing more severe hair loss, even before visible symptoms appear. By combining microbiome analysis with machine learning, this research offers a potential breakthrough for early diagnosis and personalized treatments, changing how we approach hair loss and offering new hope for managing the condition more effectively.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0054825"},"PeriodicalIF":5.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiome of the human facial skin is unique compared to that of other hominids.","authors":"Samuel Degregori, Melissa B Manus, Evan B Qu, Calen P Mendall, Jacob S Baker, Lydia M Hopper, Katherine R Amato, Tami D Lieberman","doi":"10.1128/msystems.00081-25","DOIUrl":"https://doi.org/10.1128/msystems.00081-25","url":null,"abstract":"<p><p>The human facial skin microbiome is remarkably similar across all people sampled to date, dominated by facultative anaerobe <i>Cutibacterium</i>. The origin of this genus is unknown, with no close relatives currently described from samples of primate skin. This apparent human-specific bacterial taxon could reflect the unique nature of human skin, which is significantly more oily than that of our closest primate relatives. However, previous studies have not sampled the facial skin microbiome of our closest primates. Here, we profiled the skin microbiome of zoo-housed chimpanzees (<i>Pan troglodytes</i>) and gorillas (<i>Gorilla gorilla gorilla</i>), alongside their human care staff, using both 16S and shotgun sequencing. We showed that facial skin microbiomes differ significantly across host species, with humans having the lowest diversity and the most unique community among the three species. We were unable to find a close relative of <i>Cutibacterium</i> on either chimpanzee or gorilla facial skin, consistent with human specificity. Hominid skin microbiome functional profiles were more functionally similar compared to their taxonomic profiles. However, we still found notable functional differences, including lower proportions of fatty acid biosynthesis in humans, consistent with microbes' reliance on host-derived lipids. Our study highlights the uniqueness of the human facial skin microbiome and supports a horizontal acquisition of its dominant resident from a yet unknown source.IMPORTANCEUnderstanding how and why human skin bacteria differ from our closest animal relatives provides crucial insights into human evolution and health. While we have known that human facial skin hosts distinct bacteria-particularly <i>Cutibacterium acnes</i>-we did not know if these bacteria and their associated genes were also present on the faces of our closest relatives, chimpanzees and gorillas. Our study shows that human facial skin hosts markedly different bacteria than other primates, with <i>C. acnes</i> being uniquely abundant on human faces. This finding suggests that this key bacterial species may have adapted specifically to human skin, which produces more oils than other primates.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0008125"},"PeriodicalIF":5.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental diversity of <i>Candidatus</i> Babelota and their relationships with protists.","authors":"Louis Weisse, Lucile Martin, Bouziane Moumen, Yann Héchard, Vincent Delafont","doi":"10.1128/msystems.00261-25","DOIUrl":"https://doi.org/10.1128/msystems.00261-25","url":null,"abstract":"<p><p><i>Ca</i>. Babelota is a phylum of strictly intracellular bacteria whose representatives are commonly detected in various environments through metagenomics, though their presence, ecology, and biology have never been addressed so far. As a group of strict intracellular, we hypothesize that their presence, occurrence, and abundance heavily depend on their hosts, which are known as heterotrophic protists, based on few described isolates. Here, we conducted a sampling campaign allowing to characterize protists and associated bacterial communities, using high-throughput sequencing. In parallel, a systematic enrichment of protists from samples was performed to attempt characterization and isolation of new <i>Ca</i>. Babelota within native hosts. We found that <i>Ca</i>. Babelota are among the most widespread phylum among the rare ones. Protist enrichments are allowed in certain cases to enrich as well for <i>Ca</i>. Babelota, which could be visualized <i>in vivo</i> infecting protist cells. Though cosmopolitan, <i>Ca</i>. Babelota diversity was highly site-specific. Cooccurrence analyses allowed to retrieve well-known as well as new putative associations involving numerous protists of various trophic regimes. The combination of approaches developed in this study enhances our understanding of <i>Ca</i>. Babelota ecology and biology, while paving the way for future isolation of new members of this elusive phylum, which could have huge impact on protists-and ecosystems-functioning.IMPORTANCEOur understanding of microbial diversity surrounding us and colonizing the environment has been dramatically impacted by the advent of DNA-based analyses. Such progress helped shine a new light on numerous lineages of yet-to-be-characterized microbes, whose ecology and biology are basically unknown. Among those uncharacterized clades is the <i>Candidatus</i> Babelota, a bacterial phylum for which parasitism seems to be an ancestral trait. All known <i>Ca.</i> Babelota thrive by infecting phagotrophic protist hosts, thereby impacting this basal link of the trophic chain. The <i>Ca.</i> Babelota constitutes a model that stands out, as phylum-wide conserved parasitism has only been described in one previous occurrence for Bacteria, with the Chlamydiota. Thus, exploring the intricate interplay between <i>Ca.</i> Babelota and their protist hosts will advance our knowledge of bacterial diversity, their ecology, and global impact on ecosystem functioning.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0026125"},"PeriodicalIF":5.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage DisCo: targeted discovery of bacteriophages by co-culture.","authors":"Eleanor A Rand, Natalia Quinones-Olvera, Kesther D C Jean, Carmen Hernandez-Perez, Siân V Owen, Michael Baym","doi":"10.1128/msystems.01644-24","DOIUrl":"https://doi.org/10.1128/msystems.01644-24","url":null,"abstract":"<p><p>Phages interact with many components of bacterial physiology from the surface to the cytoplasm. Although there are methods to determine the receptors and intracellular systems a specified phage interacts with retroactively, finding a phage that interacts with a chosen piece of bacterial physiology <i>a priori</i> is very challenging. Variation in phage plaque morphology does not to reliably distinguish distinct phages, and therefore many potentially redundant phages may need to be isolated, purified, and individually characterized to find phages of interest. Here, we present a method in which multiple bacterial strains are co-cultured on the same screening plate to add an extra dimension to plaque morphology data. In this method, <u>phage dis</u>covery by <u>co</u>-culture (Phage DisCo), strains are isogenic except for fluorescent tags and one perturbation expected to impact phage infection. Differential plaquing on the strains is easily detectable by fluorescent signal and implies that the perturbation made to the surviving strain in a plaque prevents phage infection. We validate the Phage DisCo method by showing that characterized phages have the expected plaque morphology on Phage DisCo plates and demonstrate the power of Phage DisCo for multiple targeted discovery applications, from receptors to phage defense systems.IMPORTANCEIn this work, we describe a targeted phage discovery method that allows immediate isolation of phages with specific traits. Currently, to find a phage with specific properties, huge libraries of phages must be collected and screened retroactively. This assay, Phage Discovery by Co-culture (Phage DisCo), works by co-culture of host strains that are identical except for one perturbation that may interfere with phage infection and a unique fluorescent marker. These strains are co-cultured with an environmental sample of interest in traditional plaque assay format, making phage characteristics easily identifiable by fluorescent signal after imaging of the screening plate. We validate that Phage DisCo can identify phages with specific properties, even when these phages are rare in samples. This approach allows rapid exploration of the diversity within phage samples with vastly streamlined processes, and we anticipate it will be widely adopted within the phage discovery field.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0164424"},"PeriodicalIF":5.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of microbiome in cystic fibrosis clinical outcomes through a mediation analysis.","authors":"Seda Sevilay Koldaş, Osman Uğur Sezerman, Emel Timuçin","doi":"10.1128/msystems.00196-25","DOIUrl":"https://doi.org/10.1128/msystems.00196-25","url":null,"abstract":"<p><p>Human microbiome plays a crucial role in host health and disease by mediating the impact of environmental factors on clinical outcomes. Mediation analysis is a valuable tool for dissecting these complex relationships. However, existing approaches are primarily designed for cross-sectional studies. Modern clinical research increasingly utilizes long follow-up periods, leading to complex data structures, particularly in metagenomic studies. To address this limitation, we introduce a novel mediation framework based on structural equation modeling that leverages linear mixed-effects models using penalized quasi-likelihood estimation with a debiased lasso. We applied this framework to a 16S rRNA sputum microbiome data set collected from patients with cystic fibrosis over 10 years to investigate the mediating role of the microbiome in the relationship between clinical states, disease aggressiveness phenotypes, and lung function. We identified richness as a key mediator of lung function. Specifically, <i>Streptococcus</i> was found to be significantly associated with mediating the decline in lung function on treatment compared to exacerbation, while <i>Gemella</i> was associated with the decline in lung function on recovery. This approach offers a powerful new tool for understanding the complex interplay between microbiome and clinical outcomes in longitudinal studies, facilitating targeted microbiome-based interventions.</p><p><strong>Importance: </strong>Understanding the mechanisms by which the microbiome influences clinical outcomes is paramount for realizing the full potential of microbiome-based medicine, including diagnostics and therapeutics. Identifying specific microbial mediators not only reveals potential targets for novel therapies and drug repurposing but also offers a more precise approach to patient stratification and personalized interventions. While traditional mediation analyses are ill-equipped to address the complexities of longitudinal metagenomic data, our framework directly addresses this gap, enabling robust investigation of these increasingly common study designs. By applying this framework to a decade-long cystic fibrosis study, we have begun to unravel the intricate relationships between the sputum microbiome and lung function decline across different clinical states, yielding insights that were previously unknown.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0019625"},"PeriodicalIF":5.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The characteristics of tissue microbiota in different anatomical locations and different tissue types of the colorectum in patients with colorectal cancer.","authors":"Lei Liu, Jianguo Shi, Hui Wang, Hansong Du, Jia Yang, Kai Wei, Zhuohui Zhou, Moli Li, Shuai Huang, Lifang Zhan, Guolong Li, Yongling Lv, Hexiao Shen, Wei Cai","doi":"10.1128/msystems.00198-25","DOIUrl":"https://doi.org/10.1128/msystems.00198-25","url":null,"abstract":"<p><p>The gut microbiota is intricately associated with the onset and progression of colorectal cancer (CRC), leading to significant interest in developing prevention and treatment strategies that leverage gut microbiota. In this study, we collected 57 samples from 19 CRC patients, comprising cancerous tissue, paracancerous tissue, and normal mucosa. Utilizing metagenomic sequencing and bioinformatics analysis, we identified differences in the microbiomes and their functional characteristics across the various tissue types. The results indicated that species such as <i>Alistipes putredinis</i> were predominantly found in normal tissues, while <i>Pseudomonas putida</i> was enriched in paracancerous tissue, and <i>Malassezia restricta</i> was prevalent in cancerous tissues. Furthermore, the microbial functions exhibited variability among the different tissue types. Random forest analysis suggested that <i>Moraxella osloensis</i> may be implicated in the onset and progression of colorectal cancer. We also classified the patients into three subgroups based on the anatomical location of the colorectum: right-sided colon, left-sided colon, and rectum. The subgroup analysis revealed that the microbiota enriched in normal mucosa and paracancerous tissue varied across different anatomical sites. These findings not only elucidate the characteristics of the microbiomes in the normal mucosa, paracancerous tissue, and cancerous tissues of CRC patients, thereby providing new potential targets for clinical diagnosis and treatment, but also contribute to the existing microbiome data pertinent to CRC research.IMPORTANCEThis study provides crucial insights into the relationship between gut microbiota and colorectal cancer (CRC) by analyzing microbial communities in different tissue types and anatomical locations of CRC patients. We identified distinct microbial signatures, such as <i>Alistipes putredinis</i> in normal tissues and <i>Malassezia restricta</i> in cancerous tissues, indicating location-specific microbiomes with unique functional attributes. These findings suggest potential new biomarkers or therapeutic targets for CRC. The observed microbiota variations among right-sided colon, left-sided colon, and rectum cancers underscore the heterogeneity of CRC, pointing toward more personalized treatment strategies. By enhancing our understanding of the microbiome's role in CRC, this research paves the way for innovative diagnostic tools and targeted therapies tailored to individual patient profiles. This work is essential for advancing clinical approaches to CRC management.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0019825"},"PeriodicalIF":5.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteopontin protects from ovalbumin-induced asthma by preserving the microbiome and the intestinal barrier function.","authors":"Jinli Huang, Hongyu Qiao, Qiuhong Li, Yi Zhang, Chenyu Zhang, Hui Su, Xin Sun","doi":"10.1128/msystems.00389-25","DOIUrl":"https://doi.org/10.1128/msystems.00389-25","url":null,"abstract":"<p><p>The gut and lung microbiota are associated with asthma. Osteopontin (OPN) is an important cytokine associated with several inflammatory diseases. The potential role of OPN in the asthma-associated microbiome remains poorly understood. Here, we investigated whether OPN could moderate asthma by affecting the gut and lung microbiota. Our results showed that compared with wild-type (WT) mice, Spp1^-/- mice exhibited immune cell infiltration in the lung, OVA-specific IgG1, increased levels of Th2- and Th17-related inflammatory factors, and decreased levels of Th1-related inflammatory factors and forkhead box P3 (FOXP3) expression, resulting in a Th1/Th2 and Th17/Treg imbalance. In addition, gut structure was impaired, and expression of tight junction-related proteins was reduced in Spp1^-/- mice, which disrupted gut barrier function. Importantly, OPN-deficient significantly aggravated gut and lung microbiota dysbiosis in OVA-induced asthmatic mice. The results of high-throughput 16S rRNA sequencing demonstrated that OPN-deficient mice showed a substantial reduction in beneficial gut and lung bacteria (<i>Bacteroidetes</i>, <i>Lactobacillus</i>, <i>Allobaculum</i>), and an OVA-induced increase in the abundance of bacteria associated with potentially pathogenic gut and lung (<i>Epsilonbacteraeota</i>, <i>Helicobacter</i>, <i>Desulfovibrio</i>, <i>Oscillibacter</i>)-associated bacteria was elevated in abundance. <i>Allobaculum</i> was negatively correlated with interleukin-4 and GATA-3 and was positively correlated with interferon gamma and FOXP3. Moreover, through fecal microbiota transplantation, we found that OVA-induced IgE and IgG1 levels were reduced in OPN-deficient asthmatic mice, Th1/Th2 and Th17/Treg balance was maintained, gut barrier function was improved, and microbiome changes in OPN-deficient mice were compensated for, with an elevated abundance of <i>Allobaculum</i> and reduced abundance of <i>Desulfovibrio</i> and <i>Oscillibacter</i>. We further discovered that OPN deficiency reduces FOXP3 expression and decreases <i>Lactobacillus</i> colonization through activation of the PD-1/PD-L1 pathway in the intestine and lung. The present study suggests that OPN may moderate OVA-induced asthma by modulating the gut and lung microbiota.</p><p><strong>Importance: </strong>Osteopontin deficiency exacerbated asthmatic airway inflammation, an effect associated with microbiota dysbiosis, impaired intestinal barrier function, and increased PD-1/PD-L1 expression and thus decreased Treg cell function. The study provides clinicians with new insights into asthma mechanisms and can also lead to new ideas for asthma treatment.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0038925"},"PeriodicalIF":5.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}