bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2025–07–06
twenty-two papers selected by
Chun-Chi Chang, Lunds universitet
  1. The double-edged nature of trained immunity.
  2. IFNγ-induced memory in human macrophages is not sustained by epigenetic changes but the durability of the cytokine itself.
  3. Epigenetic and metabolic regulation of macrophage responsiveness and memory.
  4. Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.
  5. Corrigendum: 17β-Estradiol promotes trained immunity in female against sepsis via regulating nucleus translocation of RelB.
  6. Covalent Organic Frameworks-Delivered Reuterin Drives Trained Immunity in Tumor-Associated Macrophages to Enhance Melanoma Immunotherapy via Glycerophospholipid Metabolism.
  7. Advances in Microbiome Research: Implications for Infectious Disease Management and Treatment.
  8. The vaccine we all wear: Skin microbiota can be engineered into topical vaccines.
  9. Comprehensive characterization of human alveolar epithelial cells cultured for 28 days at the air-liquid interface.
  10. Targeting innate immune sensors for therapeutic strategies in infectious diseases.
  11. Current insights into insect immune memory.
  12. Arginine at the host-pathogen interface.
  13. Airway Organoid Models as Pivotal Tools for Unraveling Molecular Mechanisms and Therapeutic Targets in Respiratory Diseases: A Literature Review.
  14. Intraspecies warfare restricts strain coexistence in human skin microbiomes.
  15. Lessons from cross-pathogen studies: understanding the metabolic rewiring of macrophages upon infection.
  16. Maintaining immune barriers.
  17. The Impact of Antibiofilm Strategies in Controlling Microbial Colonization.
  18. Next stop, precision: targeted therapies for Staphylococcus aureus infections.
  19. Circadian metabolism in myeloid cells.
  20. Combination of phages and antibiotics with enhanced killing efficacy against dual-species bacterial communities in a three-dimensional lung epithelial model.
  21. Microglial immune memory in Parkinson's and Huntington's diseases: epigenetics, triggers, and therapies.
  22. Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification.
  1. Elife. 2025 Jul 03. pii: e107787. [Epub ahead of print]14
    The double-edged nature of trained immunity.
    Chrissy M Leopold Wager, Larry S Schlesinger.
      Trained immunity in alveolar macrophages can lead to damaging lung inflammation, confirming the importance of context in this phenomenon.
    Keywords:  acute lung injury; alveolar macrophage; beta-glucan; immunology; inflammation; mouse; trained immunity
    DOI:  https://doi.org/10.7554/eLife.107787
  2. bioRxiv. 2025 Jun 17. pii: 2025.06.12.659073. [Epub ahead of print]
    IFNγ-induced memory in human macrophages is not sustained by epigenetic changes but the durability of the cytokine itself.
    Aleksandr Gorin, Noa Harriott, Vyas Koduvayur, Quen J Cheng, Alexander Hoffmann.
      Macrophages, as key sentinel cells of the innate immune system, can retain memory of prior stimulus exposure. Interferon gamma (IFNγ) plays a central role in maintaining trained immunity in vivo and can induce potent memory in macrophages. Such memory is associated with the formation of de novo enhancers that alter gene expression responses to subsequent stimuli. However, how such enhancers are maintained after cytokine exposure remains unclear. We report that durable IFNγ-induced enhancers can last for days after cytokine washout, yet the underlying persistence mechanism is not cell-intrinsic. IFNγ-treated macrophages continue to exhibit JAK/STAT signaling days after cytokine removal. Blocking IFNγ signaling with a JAK inhibitor or anti-IFNγ neutralizing antibodies after cytokine removal is sufficient to reverse IFNγ-induced enhancers and erase the potentiated state of the treated macrophages. Our findings suggest that epigenetic changes in macrophages do not inherently encode innate immune memory or a "potentiated" macrophage state, but in fact are themselves dependent on ongoing cytokine signaling. These findings suggest new possibilities for pharmacologic interventions to reverse aberrantly trained immune states associated with pathology.
    DOI:  https://doi.org/10.1101/2025.06.12.659073
  3. J Immunol. 2025 Jul 01. pii: vkaf135. [Epub ahead of print]
    Epigenetic and metabolic regulation of macrophage responsiveness and memory.
    Maria G Daskalaki, Ioanna Lapi, Avery Ellen Hurst, Ahmed Al-Qahtani, Eleni Vergadi, Christos Tsatsanis.
      Macrophages, the central mediators of innate immune responses, can adapt and build nonspecific memory, also known as innate immune memory or trained immunity. Training of macrophages occurs through epigenetic changes and metabolic rewiring, which fuels macrophage responsiveness. In addition to training in response to infectious insults, macrophage responsiveness can be modulated by pathogenic de-regulation of hormones, cytokines, or adipokines, which similarly induce epigenetic changes in inflammatory genes. Sex specific differences in macrophage responsiveness to TLR ligands have been described, with sex hormones playing a crucial role in shaping the epigenetic landscape and regulating inflammatory responses. Chronic metabolic disorders, such as obesity and type 2 diabetes, also affect macrophage responsiveness. In particular, insulin resistance impairs Akt signaling in macrophages in an Akt isoform-specific manner, altering their metabolism, their responsiveness to inflammatory insults and their capacity to eliminate pathogens. These functional impairments are underpinned by changes in the epigenetic landscape of macrophages. Given the short half-life of macrophages in the periphery, these long-lasting alterations in their responsiveness originate in the bone marrow at the level of hematopoietic stem and progenitor cells. Recent studies have demonstrated that exposure to TLR ligands induces immunological memory driven by changes in hematopoietic stem and progenitor cells. These changes include epigenetic alterations in histones and DNA. Herein we discuss recent evidence on the epigenetic and metabolic regulation of macrophage memory, highlight sex hormone-driven changes, describe changes driven by metabolic factors and obesity, and explore the therapeutic potential of targeting epigenetic regulators for the treatment of inflammatory diseases.
    Keywords:  Akt; epigenetics; gender; innate immunity; macrophages; memory; metabolism; obesity; sex; trained immunity
    DOI:  https://doi.org/10.1093/jimmun/vkaf135
  4. Infect Immun. 2025 Jun 30. e0049824
    Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.
    Bailey E Holder, Callista P Reber, Andrew J Monteith.
      Neutrophils are the most abundant leukocytes at sites of inflammation and form the front line of the innate immune response. Neutrophils have a relatively short lifespan compared to other cell types, as they have streamlined their metabolic processes to support an arsenal of antimicrobial functions to combat invading pathogens at the cost of maximizing ATP output. To elicit antimicrobial stress, neutrophils rewire their glycolytic pathways to sustain phagocytosis and the oxidative burst and modify their mitochondrial metabolism to dictate degranulation or release of neutrophil extracellular traps. While many of these effector functions are sufficient to protect the "healthy" host from infection, chronic diseases disrupting metabolic and inflammatory homeostasis render the host susceptible to more frequent and severe bacterial infections. With the growing incidence of many metabolic and autoimmune diseases, a clearer understanding of the mechanisms regulating or disrupting neutrophil antimicrobial processes is required. This review focuses on the relationship between neutrophil function and metabolism and what is known about how this impacts autoimmune and metabolic diseases and/or disorders in the case of bacterial infection.
    Keywords:  bacterial infection; diabetes; glycolysis; inflammation; metabolism; mitochondria; neutrophils; obesity; pentose phosphate pathway; systemic lupus erythematosus
    DOI:  https://doi.org/10.1128/iai.00498-24
  5. Front Immunol. 2025 ;16 1629629
    Corrigendum: 17β-Estradiol promotes trained immunity in female against sepsis via regulating nucleus translocation of RelB.
    Zhiheng Sun, Yuchen Pan, Junxing Qu, Yujun Xu, Huan Dou, Yayi Hou.
      [This corrects the article DOI: 10.3389/fimmu.2020.01591.].
    Keywords:  estradiol; gender difference; macrophages; sepsis; trained immunity
    DOI:  https://doi.org/10.3389/fimmu.2025.1629629
  6. Adv Sci (Weinh). 2025 Jun 30. e04784
    Covalent Organic Frameworks-Delivered Reuterin Drives Trained Immunity in Tumor-Associated Macrophages to Enhance Melanoma Immunotherapy via Glycerophospholipid Metabolism.
    Jian-Gang Zhang, Xiao-Mei Zhang, Xi Wu, Cheng-Kai Zhou, Zhen-Zhen Liu, Xue-Yue Luo, Liang Zhang, Wei Chen, Yong-Jun Yang.
      The gut microbiota is increasingly recognized as a promising therapeutic target in cancer treatment. However, the specific mechanisms by which gut bacteria and their metabolites exert therapeutic effects in melanoma remain poorly understood. In this study, it is unexpectedly demonstrated that prophylactic supplementation with Limosilactobacillus reuteri exhibits significant tumor-suppressive properties, primarily mediated by its secreted metabolite, reuterin. This metabolite induces trained immunity through macrophage metabolic reprogramming, thereby enhancing antitumor immune responses. Mechanistically, this process involves stabilizing HIF-1α via the AHR-ROS signaling pathway, enhancing glycerophospholipid metabolism, and elevating arachidonic acid levels, thereby amplifying the trained immunity response. Similar to reuterin, arachidonic acid also induces trained immunity and facilitates macrophage-mediated tumor cell killing. To enhance its therapeutic efficacy, reuterin is encapsulated in covalent organic frameworks (COFs). COF-Reuterin demonstrates superior effects in tumor-associated macrophages (TAMs), remodulating intratumor bacteria and directly facilitating tumor cell killing. Notably, COF-Reuterin demonstrates superior therapeutic efficacy compared to cisplatin. Furthermore, COF-Reuterin reprogrammed TAMs from an M2 to an M1 phenotype, increasing CD8+ T cell infiltration and decreasing myeloid-derived suppressor cells (MDSCs), reshaping the immunosuppressive tumor microenvironment. These findings highlight the potential of probiotics and their metabolites in the metabolic reprogramming of TAMs, offering a promising cancer therapeutic approach.
    Keywords:  Limosilactobacillus reuteri; intratumor bacteria; melanoma; reuterin; trained immunity; tumor‐associated macrophages
    DOI:  https://doi.org/10.1002/advs.202504784
  7. Recent Adv Antiinfect Drug Discov. 2025 Jul 02.
    Advances in Microbiome Research: Implications for Infectious Disease Management and Treatment.
    Anas Islam.
       INTRODUCTION: The human microbiome plays a pivotal role in health and disease, with microbial imbalances (dysbiosis) increasingly linked to heightened susceptibility to infections and exacerbated disease severity. This review explores how the microbiome confers protection through mechanisms, such as colonization resistance, immune modulation, and antimicrobial metabolite production, while also examining its potential as a predictive tool for infection risk and outcomes, as exemplified in COVID-19.
    METHODS: This article synthesizes current literature on microbiome dynamics, leveraging advances in high-throughput sequencing, bioinformatics, and machine learning to analyze microbial profiles and identify biomarkers. It evaluates microbiome-based therapeutic strategies, including probiotics, prebiotics, and engineered microbes, and assesses challenges in translating these approaches into clinical practice.
    RESULTS: Microbiome profiles demonstrate prognostic value in predicting infection risk and severity, supported by enhanced analytical tools that enable precise biomarker discovery for diagnostics and personalized medicine. Therapeutic interventions show promise in restoring microbial balance and combating infections, though clinical adoption is hindered by variability, regulatory hurdles, and the need for standardized methodologies.
    CONCLUSION: Integrating microbiome insights into clinical practice requires rigorous clinical trials, standardized protocols, and resolution of ethical and regulatory challenges. Future research should focus on elucidating microbiome-host-pathogen interactions and developing targeted interventions, and advanced computational models are critical to unlocking the full potential of microbiome-based diagnostics and therapeutics for infectious disease management.
    Keywords:  Microbiome; colonization resistance; dysbiosis; immune modulation; infectious disease; microbial imbalance; microbiome-based therapies.
    DOI:  https://doi.org/10.2174/0127724344384934250624040634
  8. Science. 2025 Jul 03. 389(6755): 37-38
    The vaccine we all wear: Skin microbiota can be engineered into topical vaccines.
    Djenet Bousbaine.
      Skin microbiota can be engineered into topical vaccines.
    DOI:  https://doi.org/10.1126/science.adz0485
  9. Sci Rep. 2025 Jul 02. 15(1): 22995
    Comprehensive characterization of human alveolar epithelial cells cultured for 28 days at the air-liquid interface.
    Ikuya Tanabe, Shinkichi Ishikawa.
      Lung epithelia are exposed to various substances in the atmosphere through breathing. To investigate the mechanisms and treatments for respiratory diseases caused by these substances, robust in vitro lung epithelial models are essential. This study aimed to develop an in vitro alveolar epithelial model using primary human pulmonary alveolar epithelial cells (HPAEpiCs). HPAEpiCs were cultured at an air-liquid interface (ALI) for 28 days in a medium supplemented with three small molecules: Y-27632, A-83-01, and CHIR99021. The characteristics of the ALI-cultured cells were then analyzed. Immunostaining revealed that many cells expressed alveolar type 2 (AT2) cell markers, such as surfactant protein B and prosurfactant protein C. Single-cell gene expression analysis further confirmed that the majority of the cells expressed genes reported to be highly expressed in AT2 cells. The apical surface of the ALI-cultured HPAEpiCs was covered with a liquid containing a variety of lipids and proteins known to be present in lung surfactant in vivo. Our data demonstrate that 28 days of ALI culture promoted the differentiation of HPAEpiCs into AT2 cells capable of secreting lung surfactant components. This ALI culture model containing differentiated AT2 cells could be valuable for investigating the mechanisms and treatments for respiratory diseases.
    Keywords:  A-83-01; Air-liquid interface culture; Alveolar epithelial cells; CHIR99021; Lung surfactant; Y-27632
    DOI:  https://doi.org/10.1038/s41598-025-07219-8
  10. J Microbiol. 2025 Jun;63(6): e2503009
    Targeting innate immune sensors for therapeutic strategies in infectious diseases.
    Seyun Shin, Young Ki Choi, SangJoon Lee.
      The innate immune system relies on innate immune sensors, such as pattern recognition receptors (PRRs), to detect pathogens and initiate immune responses, crucial for controlling infections but also implicated in inflammatory diseases. These innate immune sensors, including Toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I-like receptors (RLRs), absent in melanoma 2 (AIM2), and Z-DNA binding protein 1 (ZBP1) trigger signaling pathways that produce cytokines, modulating inflammation and cell death. Traditional therapies focus on directly targeting pathogens; however, host-targeting therapeutic strategies have emerged as innovative approaches to modulate innate immune sensor activity. These strategies aim to fine-tune the immune response, either enhancing antiviral defenses or mitigating hyperinflammation to prevent tissue damage. This review explores innate immune sensor-based therapeutic approaches, including inhibitors, agonists, and antagonists, that enhance antiviral defense or suppress harmful inflammation, highlighting innate immune sensors as promising targets in infectious and inflammatory disease treatment.
    Keywords:  cell death; infection; inflammation; innate immunity; pathogen
    DOI:  https://doi.org/10.71150/jm.2503009
  11. Elife. 2025 Jul 01. pii: e105011. [Epub ahead of print]14
    Current insights into insect immune memory.
    Gabriela Krejčová, Adam Bajgar.
      Traditionally, insects have been thought to be entirely dependent on their innate immune system, which has little capacity for the acquisition of experience from previous infections. However, much experimental evidence has challenged this view, showing that insects can develop long-term, pathogen-specific immune memory, which in some cases can be transmitted to offspring. Although significant progress has been made in this area, the underlying mechanism is still not fully understood, and a number of fundamental questions remain unanswered. In this review, we present an overview of documented cases of insect immune memory and summarize the experimental evidence in support of the prevailing hypotheses on the mechanism of antiviral and antibacterial immune memory in insects. We also highlight key questions that remain unanswered and discuss Drosophila melanogaster as a powerful model organism for investigating the mechanisms of innate immune memory formation. Finally, we evaluate the significance of this research and explore the potential for insect vaccination.
    Keywords:  Dscam; evolutionary biology; hemocytes; immune memory; immunology; inflammation; insect immunity; insect vaccination; trained immunity
    DOI:  https://doi.org/10.7554/eLife.105011
  12. Infect Immun. 2025 Jul 03. e0061224
    Arginine at the host-pathogen interface.
    Brooke E Ryan, Laura A Mike.
      Nutrient availability shapes the course of infection. Arginine, a conditionally essential amino acid, plays a crucial role in both host immune defense and pathogen metabolism. As a precursor for nitric oxide production, arginine supports immune functions in multiple immune cell types to control infections. However, it also serves as a signal for pathogens that promotes bacterial survival and growth. A plethora of recent studies have shown that arginine functions not only as a metabolic substrate but also as a key environmental cue that can alter cyclic diguanylate levels. Arginine availability regulates multiple bacterial processes in both Gram-positive and Gram-negative species including toxin production, biofilm formation, Type III secretion system, swarming, persistence, and immune evasion. In this way, arginine levels can shape how pathogens behave within the host environment. This review examines how fluctuations in arginine levels across different host niches influence microbial pathogenesis and highlights the complex interplay between arginine availability and bacterial behavior. Understanding the role of arginine in host-pathogen interactions may provide new therapeutic strategies to combat infections by targeting bacterial responses to this crucial nutrient.
    Keywords:  AhrC; ArgR; arginine; biofilm; gene regulation; metabolic regulation; secretion systems; swarming; toxins
    DOI:  https://doi.org/10.1128/iai.00612-24
  13. Ther Clin Risk Manag. 2025 ;21 975-986
    Airway Organoid Models as Pivotal Tools for Unraveling Molecular Mechanisms and Therapeutic Targets in Respiratory Diseases: A Literature Review.
    Shu-Ping Jiang, Bing-Qi Lin, Xing-Qiang Zhou, Min-Hua Li, Zhen-Cheng Feng, Yue-Ying Qin, Shi-Qi Lin, Zi-Qing Zhou, Yang Peng, Lian Li.
      Respiratory inflammatory and infectious diseases continue to impose a substantial global health burden, compounded by persistent gaps in understanding their pathogenic mechanisms and limited therapeutic advancements. To address these challenges, this review systematically analyzed literature from PubMed, Web of Science, and Scopus databases (2005-2025) to evaluate the evolution and applications of airway organoid models in respiratory disease research. Key findings include: (1) the convergence of traditional culture techniques with advanced methodologies - including 3D matrix embedding, bioprinting and organoids-on-chips technologies - has enabled unprecedented recapitulation of human airway architecture and multicellular interactions; (2) these novel models provide unique insights into disease pathogenesis, host-microbe dynamics, and drug response variability; (3) the inherent capacity to maintain native cellular diversity and disease-associated phenotypes positions airway organoids as crucial platforms for personalized medicine approaches. Collectively, these advances establish airway organoids as transformative tools that bridge conventional in vitro models and clinical reality. Looking ahead, coupling organs-on-chips platforms with microgravity culture and single-cell lineage tracing will catalyze fundamental breakthroughs in respiratory disease research.
    Keywords:  airway organoids; precision treatment; respiratory diseases; technological progress
    DOI:  https://doi.org/10.2147/TCRM.S526727
  14. Nat Microbiol. 2025 Jul;10(7): 1581-1592
    Intraspecies warfare restricts strain coexistence in human skin microbiomes.
    Christopher P Mancuso, Jacob S Baker, Evan B Qu, A Delphine Tripp, Ishaq O Balogun, Tami D Lieberman.
      Determining why only a fraction of encountered or applied strains engraft in a given person's microbiome is crucial for understanding and engineering these communities. Previous work has established that metabolic competition between bacteria can restrict colonization success in vivo, but other mechanisms may also prevent successful engraftment. Here we combine genomic analysis and high-throughput agar competition assays to demonstrate that intraspecies warfare presents a significant barrier to strain coexistence in the human skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis isolates cultured from 18 people from 6 families. We find that intraspecies antagonisms are abundant, mechanistically diverse, independent of strain relatedness and consistent with rapid evolution via horizontal gene transfer. Critically, these antagonisms are significantly depleted among strains residing on the same person relative to random assemblages, indicating a significant in vivo role. Wide variation in antimicrobial production and resistance suggests trade-offs between these factors and other fitness determinants. Together, our results emphasize that accounting for intraspecies warfare may be essential to the design of long-lasting probiotic therapeutics.
    DOI:  https://doi.org/10.1038/s41564-025-02041-4
  15. Front Cell Infect Microbiol. 2025 ;15 1584777
    Lessons from cross-pathogen studies: understanding the metabolic rewiring of macrophages upon infection.
    Marisol Perez-Toledo, Alba Llibre.
      Bacterial infections remain a significant cause of morbidity and mortality globally. Compounding the issue is the rise of antimicrobial-resistant strains, which limit treatment options. Macrophages play key roles in the immunity and pathogenicity of intracellular infections, such as those caused by Mycobacterium tuberculosis and Salmonella. Recent advancements have enabled us to better understand how the host orchestrates immune responses to fight these infections and, specifically how the infected cell rewires its metabolism to face this challenge. The engagement of the host cell in specific metabolic pathways impacts cell function and behaviour, and ultimately, infection outcomes. In this perspective, we summarise key findings regarding the metabolic adaptations in macrophages induced by Mycobacterium tuberculosis and Salmonella infections. We also explore how cross-pathogen studies can deepen our insights into infection biology to improve therapeutic design.
    Keywords:  Mycobacterium tuberculosis; Salmonella typhimurium; host-direct therapies; macrophage; metabolism rewiring
    DOI:  https://doi.org/10.3389/fcimb.2025.1584777
  16. Nat Immunol. 2025 Jul;26(7): 977
    Maintaining immune barriers.
      
    DOI:  https://doi.org/10.1038/s41590-025-02222-7
  17. Curr Microbiol. 2025 Jun 30. 82(8): 351
    The Impact of Antibiofilm Strategies in Controlling Microbial Colonization.
    Binimol Jacob Karayamparambil, Kayeen Vadakkan, Sinjumol Thomas.
      Biofilms play a crucial role in persistent infections and antibiotic resistance owing to their structural complexity and protective matrices. This review focuses on current antibiofilm techniques to avoid or inhibit microbial colonisation. Key approaches involve the employing of antimicrobial peptides, quorum sensing inhibitors, quorum quenching agents, matrix-degrading enzymes, nanoparticles, and bacteriophages. These techniques inhibit biofilm formation, increase antimicrobial penetration, and impede biofilm integrity. The focus is on Pseudomonas aeruginosa and Staphylococcus aureus, two clinically relevant biofilm-forming bacteria. Quorum quenching, which interrupts microbial communication networks, has emerged as a viable technique for inhibiting pathogenesis and biofilm growth. Efforts have been made to identify various compounds used for inhibiting quorum Sensing. Various plant extracts and enzymes have been proven to affect quorum sensing profoundly. Another strategy is to inhibit the genes responsible for biofilm formation. Certain genes can be upregulated or downregulated to prevent biofilm formation, or component production can be minimised. A multidisciplinary strategy that incorporates these tactics can give effective approaches for treating biofilm-related illnesses in healthcare and industrial settings.
    DOI:  https://doi.org/10.1007/s00284-025-04345-4
  18. Future Microbiol. 2025 Jul 03. 1-3
    Next stop, precision: targeted therapies for Staphylococcus aureus infections.
    Frank J Hernandez.
      
    Keywords:  Antibiotics; Bacteriophages; Therapeutic Oligonucleotides Activated by Nucleases (TOUCAN); antibody-drug conjugates (ADC); precision medicine
    DOI:  https://doi.org/10.1080/17460913.2025.2528416
  19. Life Metab. 2025 Aug;4(4): loaf018
    Circadian metabolism in myeloid cells.
    Yingxi Xu, Chen Wang, Ping-Chih Ho.
      Circadian rhythms are fundamental regulators of physiological processes, including immune function. Recent insights uncover that not only lymphocytes but also myeloid cells possess intrinsic circadian clocks that govern their behavior and function. Emerging evidence highlights how circadian regulation of metabolism critically shapes the inflammatory and tissue-repair functions of myeloid subsets. Furthermore, mitochondrial dynamics, a key metabolic feature, are under circadian control and influence antigen presentation and effector functions. Here, we review the interplay between circadian clocks, metabolism, and myeloid immunity, discussing their therapeutic opportunities for optimizing vaccination, infection management, and immunotherapy.
    Keywords:  circadian rhythms; metabolism; myeloid cell
    DOI:  https://doi.org/10.1093/lifemeta/loaf018
  20. Biofilm. 2025 Jun;9 100245
    Combination of phages and antibiotics with enhanced killing efficacy against dual-species bacterial communities in a three-dimensional lung epithelial model.
    Ergun Akturk, Graça Pinto, Lisa Ostyn, Aurélie Crabbé, Luís D R Melo, Joana Azeredo, Tom Coenye.
      Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found in biofilm-associated polymicrobial respiratory infections that are challenging to control. Studies performed in laboratory standard conditions suggest that bacterio(phages) and antibiotic combinations are more active against bacterial communities and biofilms than each agent alone. The purpose of this work was to study the antibacterial efficacy of phage-antibiotic combinations using an in vivo-like three-dimensional lung epithelial model that mimics aspects of the parental tissue, colonized by a mixed bacterial community of P. aeruginosa and S. aureus. The bacterial population was targeted by phages specific to P. aeruginosa and/or gentamicin and ciprofloxacin. The results showed that P. aeruginosa was eradicated from the dual-species community when phage treatment was followed by gentamicin and was significantly reduced when followed by ciprofloxacin. Moreover, applying phages first followed by antibiotics demonstrated superior antibacterial activity compared to simultaneous treatment or treatments with the reverse order of application. This approach also reduced the S. aureus population but not as significant as the P. aeruginosa population. Using an in vivo-like model we demonstrated that phages and antibiotics are effective against dual-species bacterial communities, particularly targeting the P. aeruginosa population. However, but the sequence in which these antimicrobials are applied significantly in fluences the effectiveness of bacterial killing.
    Keywords:  Antibiotic; Bacteriophage treatment; Dual-species bacterial community; In vivo-like model; Phage-antibiotic constructive interaction; Pseudomonas aeruginosa; Staphylococcus aureus
    DOI:  https://doi.org/10.1016/j.bioflm.2024.100245
  21. Epigenomics. 2025 Jul 01. 1-14
    Microglial immune memory in Parkinson's and Huntington's diseases: epigenetics, triggers, and therapies.
    Reema Chowdhury, Anna Hendlinger, Olaf Riess, Julia Schulze-Hentrich.
      Neurodegenerative disorders, like Parkinson's and Huntington's disease, have a profound global impact but currently lack effective treatments. Accumulations of misfolded proteins of α-synuclein and huntingtin are a common pathological hallmark in these diseases, respectiveley. Recently, the role of microglia and innate immune memory in modulating neurodegenerative diseases has been studied in more detail. This review explores the mechanisms of microglial activation in Parkinson's and Huntington's, emphasizing innate immune memory, epigenetic reprogramming, and the influence of external triggers such as lipopolysaccharides (LPS) and high-fat diets (HFD). The review also examines therapeutic strategies targeting microglia to mitigate neurodegeneration, including shifting microglial phenotypes from pro-inflammatory to anti-inflammatory states using epigenetic interventions. To support this review, a structured literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included microglia, innate immune memory, epigenetics, neuroinflammation, and disease-specific terms. Future research should focus on improving animal models, investigating environmental stressors, and developing reliable biomarkers to strengthen translational approaches for neuroinflammatory-driven neurodegenerative diseases.
    Keywords:  Huntington's disease; Parkinson's disease; epigenetics; innate immune memory; microglia
    DOI:  https://doi.org/10.1080/17501911.2025.2518909
  22. iScience. 2025 Jul 18. 28(7): 112842
    Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification.
    Qianqian Yang, Hengchao Zhang, Yan Hou, Shaoyang Gu, Lixiang Chen, Fumin Xue, Xiuyun Wu.
      Lactate plays important regulatory roles in a variety of biological events by regulating metabolic homeostasis and histone lactylation. However, the role of lactate and histone lactylation in human erythropoiesis remains unclear. Here, we explored the role of lactate in erythropoiesis by adding the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) or exogenous lactate Na-La to decrease or increase intracellular lactate levels. The results showed the inhibition of glycolysis promoted erythroid progenitors' differentiation, blocked cell cycle, and reduced colony formation of colony-forming unit-erythroid (CFU-E), whereas elevated lactate levels delayed erythroid progenitors' differentiation and promoted CFU-E colony formation. We also found lactate levels directly regulated H3K14la intensity. Furthermore, we showed changes in H3K14la abundance and gene expression of the cell cycle and division-related genes CCNB1, CFL1, CENPA, and GNAI2, which were associated with stem cell pluripotency and differentiation. In conclusion, our study reveals lactate affects cell differentiation of early erythroid progenitors by regulating gene expression through histone lactylation.
    Keywords:  Biochemistry; Cell biology; Molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2025.112842
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