bims-bac4me 2025-10-12 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2025–10–12
thirty-two papers selected by
Chun-Chi Chang, Lunds universitet

Metabolic regulation of immune memory and function of microglia.
Dexamethasone inhibits Mycobacterium tuberculosis-induced glycolysis but preserves antimicrobial function in primary human macrophages.
The impact of interferon-γ pathway on trained immunity induction by vaccination with Bacille Calmette-Guérin.
Staphylococcus aureus persistence in the lung is necessary to elicit systemic protective immunity.
Enterobacteriaceae-derived cadaverine manipulates gut macrophage metabolism.
A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics.
Multifaceted mitochondria in innate immunity.
Pseudomonas aeruginosa-secreted respiratory toxin HQNO triggers fatty acid accumulation in respiring Staphylococcus aureus, decreasing SaeRS-dependent transcriptional regulation.
Characterization of the Cellular Immune Response to Group B Streptococcal Vaginal Colonization.
Role of Antimicrobial Peptides in the Pathogenesis of Atopic Dermatitis.
Fatty acid synthase-mediated lipid droplet formation enhances macrophage killing of Staphylococcus aureus.
TAS4464, a neddylation inhibitor, mitigates Staphylococcus aureus-induced periprosthetic joint infection by modulating immunosuppressive cell functions.
Gut microbiota: a promising new target in immune tolerance.
Protocol for measuring cellular energetics through noncanonical amino acid tagging in human peripheral blood and murine tissue immune cells.
Coenzyme A Metabolism: A Key Driver of Gut Microbiota Dynamics and Metabolic Profiles.
A mother's touch: microbial guardians of early immune imprinting.
Ontogeny specification and epigenetic regulation of macrophage plasticity.
A Review on macrophage biology and its potential role in spontaneous abortion.
Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.
Microbiome: Friend or Friendly Foe.
Anti-SARS-CoV-2 Spike IgA2 Induces Inflammation by Human Macrophages.
Interspecies signaling can sensitize intrinsically resistant Streptococcus pyogenes to colistin.
Group 3 innate lymphoid cell-derived CSF2 tunes homeostasis of tissue macrophages and neutrophils.
Melatonin Confers Protection Against Multidrug-Resistant Bacterial Infections in Aged Mice Via Microbiota-Derived Butyrate.
Calycosin ameliorates inflammation and M1 macrophage polarization via Spon2 in LPS-triggered MH-S alveolar macrophages.
Microbial metabolites and their influence on the tumor microenvironment.
Engineered polysaccharides for controlling innate and adaptive immune responses.
The rise of 'nightmare bacteria': antimicrobial resistance in five charts.
Barrier dysfunction in nasal epithelium contributes to persistent inflammation in long COVID.
Layers of defense: protection from respiratory viruses by epithelial-intrinsic immunity.
Monocyte-derived macrophages support alveolar regeneration via oncostatin M post-H1N1 infection during the recovery phase.
Microbiota-derived metabolites in the epigenetic regulation of the host.

Elife. 2025 Oct 10. pii: e107552. [Epub ahead of print]14

Metabolic regulation of immune memory and function of microglia.

Nikolaos Nirakis, Sofia Dimothyra, Eleftheria Karadima, Vasileia Ismini Alexaki.

  Innate immune cells possess memory-like properties. Exposure to infections or sterile inflammation can prime them, leading to either exacerbated inflammatory responses, a process called trained immunity, or reduced responsiveness to pro-inflammatory signals, a process termed immune tolerance. Microglia, the resident innate immune cells of the central nervous system, are central players in neurodegenerative diseases. Characterizing trained immunity and tolerance in microglia is necessary for a better understanding of neurodegenerative diseases. Cell metabolic processes orchestrate microglia inflammatory responses and promote epigenetic changes shaping immune memory in microglia. Here, we review current knowledge on the role of cell metabolic pathways in microglia innate immune memory formation, focusing on glucose, glutamine, and lipid metabolism. Moreover, we address the significance of microglial immune memory in disease pathology and discuss the potential of therapeutic targeting of cell metabolic pathways in neurodegenerative disorders.

Keywords:  cell metabolism; immunology; inflammation; microglia; tolerance; training

DOI:  https://doi.org/10.7554/eLife.107552
Sci Rep. 2025 Oct 09. 15(1): 34310

Dexamethasone inhibits Mycobacterium tuberculosis-induced glycolysis but preserves antimicrobial function in primary human macrophages.

Lorraine Thong, Olivia Sandby Thomas, Oisin Ó Gallchobhair, Emily Duffin, Anjali S Yennemadi, Gina Leisching, Dearbhla M Murphy, Parthiban Nadarajan, Finbarr O'Connell, Mary P O'Sullivan, Sharee A Basdeo, Donal J Cox, Joseph Keane.

  Glucocorticoids (GC) are useful adjunctive host directed therapies (HDT) for sub-types of tuberculosis (TB). Macrophages play a central role in controlling Mycobacterium tuberculosis (Mtb) infection, relying on glycolytic reprogramming to support an effective host defence, yet the influence of GC on these important phagocytes is poorly understood. Here, we examined the impact of dexamethasone on metabolic and functional responses of primary human airway macrophages (AM) from bronchoalveolar lavage fluid and monocyte-derived macrophages (MDM). We found that dexamethasone significantly reduced basal and compensatory glycolysis in both AM and MDM, and decreased expression of the glycolytic enzyme PFKFB3. Oxidative metabolism was lower in dexamethasone AM but not MDM, indicating different specific metabolic sensitivity of macrophages. Dexamethasone also inhibited the glycolytic response to Mtb and reduced secretion of IL-1β, TNF, IL-6, IL-8, and IL-10. Dexamethasone-treated macrophages showed enhanced survival following Mtb infection and these cells had a significant reduction in bacterial burden. This antimicrobial effect was impaired when macrophages were pre-treated with bafilomycin A1, implicating that phagosomal acidification may at least in part mediate dexamethasone-induced bacterial control. Collectively, these findings demonstrate that dexamethasone reprograms human macrophage metabolism toward a less glycolytic state while preserving their ability to limit Mtb growth. These results may provide a basis for the clinical benefit of GC in some TB presentations and support the development of targeting GC therapies to macrophages, thereby mitigating inflammation without compromising host antimicrobial defence.

Keywords:  Glycolysis; Human alveolar macrophage; Immunometabolism; Mycobacterium tuberculosis; Oxidative phosphorylation; Steroid

DOI:  https://doi.org/10.1038/s41598-025-20188-2
Sci Rep. 2025 Oct 06. 15(1): 34698

The impact of interferon-γ pathway on trained immunity induction by vaccination with Bacille Calmette-Guérin.

Ekaterina Isachesku, Andrei Cismaru, Vasiliki Matzaraki, Simone J C F M Moorlag, Vera P Mourits, Valerie A C M Koeken, L Charlotte J de Bree, Leo A B Joosten, Ioana Berindan-Neagoe, Mihai G Netea.

  Bacillus Calmette-Guérin (BCG) has multiple heterologous off-target effects which extend beyond tuberculosis (TB) prophylaxis, which include protection against other non-tuberculous infections, autoimmune diseases, and tumor development. These heterologous effects are at least partially mediated by induction of trained immunity. In this study, we aimed to investigate the impact of IFNγ production capacity on induction of trained immunity in human volunteers vaccinated with BCG. We evaluated inflammation and immune activation-specific cytokine responses (IFNγ, TNF, IL-1, and IL-6) in PBMCs isolated from 323 healthy volunteers vaccinated with BCG and stimulated with either Mycobacterium tuberculosis or Staphylococcus aureus. We further assessed the impact of genetic variants in genes crucial for the biological activity of IFNγ pathway on trained immunity using single nucleotide polymorphism (SNP) genotyping. We found a significant correlation between baseline IFNγ production capacity and induction of trained immunity, as assessed by the fold-change increase in IL-6 production at both day 14 and day 90 post-vaccination compared to production before vaccination. A similar correlation was found between basal IFNγ production and increased IL-1β production at day 14 after BCG. This suggests that individuals with higher IFNγ production capacity exhibit stronger trained immunity responses post-BCG vaccination. This hypothesis is supported by the finding that SNPs in genes involved in the IFNγ biological pathway significantly influence trained immunity responses in humans. IFNγ production capacity and genetic variations in the IFNγ pathway genes impact the magnitude of trained immunity response, providing insights into the regulation of innate memory responses.

Keywords:  BCG; Cytokine response; Genetic variation; Interferon-γ; Trained immunity

DOI:  https://doi.org/10.1038/s41598-025-16350-5
Front Immunol. 2025 ;16 1587018

Staphylococcus aureus persistence in the lung is necessary to elicit systemic protective immunity.

Usha Vyshnavi Chidella, Zhaotao Li, Maureen Kleinhenz, Christopher P Montgomery.

  Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI) and pneumonia. Recurrence is common and treatment is complicated by antimicrobial resistance; therefore, it is necessary to understand the mechanisms by which the host develops protective immunity against S. aureus. We previously reported that SSTI, but not pneumonia, elicits strong S. aureus-specific antibody and T cell responses and protection against recurrent infection; these findings suggested that site-specific elicited immune responses drive protective immunity. Because S. aureus is rapidly cleared from the lung but persists in the skin, we hypothesized that bacterial persistence in the lung is necessary to elicit protective antibody and T cell responses. In this study, we tested this hypothesis using a newly described mouse model of persistent pneumonia. Indeed, persistent pneumonia and SSTI elicited strong toxin-specific antibody and CD4+ IL-17+ and IFNγ+ T cell responses, whereas transient pneumonia did not. Persistence of S. aureus in the lung was accompanied by durable systemic T and B cell expansion observed as early as 9 days after infection. Consistent with important roles for antibodies and T cells in protective immunity, SSTI and persistent pneumonia, but not transient pneumonia, elicited protection against secondary SSTI and pneumonia. Taken together, these results demonstrate that bacterial persistence in infected tissues is necessary to elicit protective immunity against recurrent infections. These findings have important implications in better understanding the mechanisms of natural immunity against S. aureus.

Keywords:  SSTI; Staphylococcus aureus; T cells; antibody; antigen persistence; pneumonia; protective immunity

DOI:  https://doi.org/10.3389/fimmu.2025.1587018
Nat Rev Immunol. 2025 Oct 07.

Enterobacteriaceae-derived cadaverine manipulates gut macrophage metabolism.

Alexandra Flemming.

DOI: https://doi.org/10.1038/s41577-025-01234-6
Nat Microbiol. 2025 Oct 10.

A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics.

Kuan-Yi Lu, Xiangbo Yang, Matthew J G Eldridge, Rongfeng Sun, Rachel T Giorgio, Benjamin I Morris, Nikki J Wagner, Brian Hardy, Matthew Axtman, Sarah E Rowe, Xiaodong Wang, Vance G Fowler, Qingyun Liu, Sophie Helaine, Kenneth H Pearce, Brian P Conlon.

Intracellular bacterial reservoirs contribute to antibiotic treatment failure by fostering metabolically dormant persister cells that are highly tolerant to killing. However, strategies to effectively target intracellular persister cells remain limited. Here we developed a high-throughput screen to identify compounds that modulate the metabolic activity of intracellular Staphylococcus aureus. The identified compound, KL1, increases intracellular bacterial metabolic activity and sensitizes persister populations of S. aureus to antibiotics, without causing cytotoxicity or bacterial outgrowth. KL1 also exhibits adjuvant activity against intramacrophage Salmonella enterica Typhimurium and Mycobacterium tuberculosis, as well as in murine infection models of S. aureus and S. Typhimurium infection. Transcriptomic analysis and further mechanistic studies reveal that KL1 modulates host immune response genes and suppresses the production of reactive species in host macrophages, alleviating a key inducer of antibiotic tolerance. Our findings highlight the potential to target intracellular persisters by stimulating their metabolism. There are two major problems in the field of antimicrobial chemotherapy-antibiotic resistance and antibiotic tolerance. Antibiotic tolerance has been frequently connected with poor treatment outcomes in the clinic. Unlike antibiotic resistance, which permits bacterial growth in the presence of drugs, antibiotic tolerance allows bacteria to withstand multiple antibiotics for prolonged periods. The extended survival of tolerant bacteria further predisposes them to evolve antibiotic resistance over time, underscoring the critical need to address antibiotic tolerance. Host interactions have been shown to induce persister formation in numerous pathogens, with the production of reactive oxygen and nitrogen species heavily implicated in the collapse of bacterial metabolic activity and entry into an antibiotic-tolerant state. Yet, tools to study or target this process remain limited. Here we developed a high-throughput screen to identify compounds that modulate intracellular S. aureus metabolism, leading to the discovery of KL1, a host-directed compound that sensitizes persisters to antibiotic killing.

DOI: https://doi.org/10.1038/s41564-025-02124-2
NPJ Metab Health Dis. 2024 May 27. 2(1): 6

Multifaceted mitochondria in innate immunity.

Eloïse Marques, Robbin Kramer, Dylan G Ryan.

The ability of mitochondria to transform the energy we obtain from food into cell phosphorylation potential has long been appreciated. However, recent decades have seen an evolution in our understanding of mitochondria, highlighting their significance as key signal-transducing organelles with essential roles in immunity that extend beyond their bioenergetic function. Importantly, mitochondria retain bacterial motifs as a remnant of their endosymbiotic origin that are recognised by innate immune cells to trigger inflammation and participate in anti-microbial defence. This review aims to explore how mitochondrial physiology, spanning from oxidative phosphorylation (OxPhos) to signalling of mitochondrial nucleic acids, metabolites, and lipids, influences the effector functions of phagocytes. These myriad effector functions include macrophage polarisation, efferocytosis, anti-bactericidal activity, antigen presentation, immune signalling, and cytokine regulation. Strict regulation of these processes is critical for organismal homeostasis that when disrupted may cause injury or contribute to disease. Thus, the expanding body of literature, which continues to highlight the central role of mitochondria in the innate immune system, may provide insights for the development of the next generation of therapies for inflammatory diseases.

DOI: https://doi.org/10.1038/s44324-024-00008-3
J Bacteriol. 2025 Oct 08. e0039525

Pseudomonas aeruginosa-secreted respiratory toxin HQNO triggers fatty acid accumulation in respiring Staphylococcus aureus, decreasing SaeRS-dependent transcriptional regulation.

Franklin Roman-Rodriguez, Nupur Tyagi, Hassan Al-Tameemi, Jeffrey M Boyd.

  Staphylococcus aureus and Pseudomonas aeruginosa are the two pathogens that colonize the airway of cystic fibrosis patients. As patients age, P. aeruginosa outcompetes S. aureus to become the predominant organism in the airway, which overlaps with worsening symptoms. This inverse correlation is partly due to the ability of P. aeruginosa to secrete secondary metabolites and virulence factors that are antagonistic to the host cells and other bacteria present. Several of these secondary metabolites inhibit S. aureus respiration. SaeRS is a two-component regulatory system that promotes the transcription of numerous virulence genes in S. aureus. The transcription of SaeRS-regulated genes is decreased as a function of respiratory status. The accumulation of intracellular fatty acids also negatively impacts the activity of SaeRS. Incubation of S. aureus with P. aeruginosa cell-free conditioned culture medium decreased the transcriptional output of the SaeRS system. Further analyses using P. aeruginosa mutant strains and chemical genetics determined that 2-heptyl-4-quinolone N-oxide (HQNO) was responsible for the SaeRS-dependent changes in gene regulation. Treatment with HQNO increased the abundance of cell-associated fatty acids. HQNO inhibits cell respiration, and the SaeRS system did not respond to HQNO treatment in a respiration-impaired S. aureus strain, which accumulates fatty acids. The data presented are consistent with a working model wherein treatment of S. aureus with HQNO inhibits respiration, increasing free fatty acid accumulation, which negatively impacts SaeRS signaling. This results in decreased expression of the SaeRS regulon, which has significant roles in pathogenesis.IMPORTANCEPseudomonas aeruginosa and Staphylococcus aureus are often co-isolated from the airways of cystic fibrosis patients. P. aeruginosa secretes non-essential metabolites that alter S. aureus physiology, providing P. aeruginosa with a competitive advantage. S. aureus can adapt to the presence of these metabolites, but the genetic mechanisms used to sense these P. aeruginosa-produced metabolites and/or the induced physiological changes are largely unknown. The S. aureus SaeRS two-component regulatory system positively regulates the expression of various virulence factors, including toxins and proteases, that facilitate adaptation to and survival in hostile host environments. This study demonstrates that the P. aeruginosa-produced respiratory toxin 2-heptyl-4-quinolone N-oxide inhibits respiration, decreasing the transcription of SaeRS-regulated genes and thereby decreasing virulence factor production. These findings could be exploited to decrease the ability of S. aureus to express virulence factors in various infection settings.

Keywords:  HQNO; Pseudomonas aeruginosa; SaeRS; Staphylococcus aureus; fatty acid; respiration

DOI:  https://doi.org/10.1128/jb.00395-25
J Innate Immun. 2025 Oct 02. 1-22

Characterization of the Cellular Immune Response to Group B Streptococcal Vaginal Colonization.

Brady L Spencer, Dustin T Nguyen, Stephanie M Marroquin, Laurent Gapin, Rebecca L O'Brien, Kelly S Doran.

INTRODUCTION: Group B Streptococcus (GBS) asymptomatic colonizes the female genital tract (FGT) but can contribute to adverse pregnancy outcomes including pre-term birth, chorioamnionitis, and neonatal infection. We previously observed that GBS elicits FGT cytokine responses, including IL-17, during murine vaginal colonization; yet the anti-GBS cellular immune response during colonization remained unknown. We hypothesized that GBS may induce cellular immunity, resulting in FGT clearance.
METHODS: Herein, we utilize depleting antibodies and knockout mice and performed flow cytometry to investigate cellular immunes responses during GBS colonization.
RESULTS: We found that neutrophils (effectors of the IL-17 response) are important for GBS mucosal control as neutrophil depletion promoted increased GBS burdens in FGT tissues. Flow cytometric analysis of immune populations in the vagina, cervix, and uterus revealed, however, that GBS colonization did not induce a marked increase in FGT CD45+ immune cells. We also found that that Vγ6+ γδ T cells comprise a primary source of FGT IL-17. Finally, using knockout mice, we observed that IL-17-producing γδ T cells are important for the control of GBS in the FGT during murine colonization.
CONCLUSIONS: Taken together, this work characterizes FGT cellular immunity and suggests that GBS colonization does not elicit a significant immune response, which may be a bacterial directed adaptive outcome. However, certain FGT immune cells, such as neutrophils and ɣδ T cells, contribute to host defense and control of GBS colonization.

DOI: https://doi.org/10.1159/000548044
J Dermatol. 2025 Oct 08.

Role of Antimicrobial Peptides in the Pathogenesis of Atopic Dermatitis.

Ge Peng, Alafate Abudouwanli, Quan Sun, Yi Tan, Wanchen Zhao, Mengyao Yang, Shan Wang, Hideoki Ogawa, Ko Okumura, François Niyonsaba.

  Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by barrier dysfunction, immune dysregulation, and microbial dysbiosis. Recent studies have highlighted the multifaceted roles of antimicrobial peptides (AMPs) both as innate defenders against microbial invasion and as regulators of immune responses and skin barrier homeostasis. This review synthesizes the current knowledge on the dysregulation of AMP expression in AD, the impact of Th2-dominant inflammation on AMP-mediated defense, and the complex relationship between AMP activity and the cutaneous microbiota (particularly in the context of Staphylococcus aureus colonization). We also explore the immunomodulatory and barrier-stabilizing functions of AMPs, emphasizing their dual roles as both protective and potentially pathogenic agents depending on their expression levels and processing. Furthermore, emerging therapeutic strategies that aim to restore AMP function (such as vitamin D signaling, aryl hydrocarbon receptor activation, and synthetic AMPs) are discussed. A deeper understanding of AMP-related mechanisms in AD may offer novel insights for precision-targeted interventions that simultaneously address inflammation, barrier repair, and microbial imbalance.

Keywords:  antimicrobial peptide; atopic dermatitis; immune modulation; skin barrier; skin microbiota

DOI:  https://doi.org/10.1111/1346-8138.17975
Cell Death Dis. 2025 Oct 07. 16(1): 715

Fatty acid synthase-mediated lipid droplet formation enhances macrophage killing of Staphylococcus aureus.

Yanping Wu, Jiaxin Shen, Shenwei Gao, Miao Li, Qingyu Weng, Kua Zheng, Chen Zhu, Zhongnan Qin, Jieyu Li, Jiafei Lou, Songmin Ying, Yinfang Wu, Zhihua Chen, Wen Li.

Macrophages play a critical role in defending against Staphylococcus aureus (S. aureus), a major human pathogen. Recently, there has been growing interest in the metabolic regulation of macrophage function; however, the specific role of lipid synthesis in macrophage activation remains poorly understood. This study demonstrates that fatty acid synthase (FASN), an enzyme integral to de novo lipogenesis, is significantly upregulated in macrophages during S. aureus infection. Notably, S. aureus engages in a functional interaction with proteasomes, inhibiting their activity through the PI3K/AKT/mTOR signaling pathway. This interaction results in reduced degradation of FASN, leading to elevated levels of this crucial enzyme. The increased expression of FASN is vital for macrophage-mediated pathogen clearance, as it facilitates the formation of lipid droplets (LDs), which in turn enhance the antimicrobial response against S. aureus, partly through the accumulation of the antimicrobial peptide CAMP. In a murine pneumonia model, deficiency of FASN correlates with increased bacterial burden, exacerbated lung inflammation, and a significant reduction in survival rates. Collectively, these findings underscore the essential role of FASN-mediated LD formation in macrophage activation and highlight potential therapeutic targets within the FASN and lipid metabolism pathways for the treatment of S. aureus pneumonia.

DOI: https://doi.org/10.1038/s41419-025-08044-7
Biomed Pharmacother. 2025 Oct 03. pii: S0753-3322(25)00816-9. [Epub ahead of print]192 118622

TAS4464, a neddylation inhibitor, mitigates Staphylococcus aureus-induced periprosthetic joint infection by modulating immunosuppressive cell functions.

Kuo-Ti Peng, Jiun-Liang Chen, Yu-Chien Hsieh, Chun-Yuan Hsiao, Chia-Ching Yang, Ju-Fang Liu, Chiang-Wen Lee, Yao-Chang Chiang, Pey-Jium Chang.

  Staphylococcus aureus (S. aureus) is a leading cause of biofilm-associated periprosthetic joint infections (PJIs), in part due to its ability to induce an immunosuppressive environment. Biofilm formation promotes the expansion of myeloid-derived suppressor cells (MDSCs) and M2 macrophages, which impair host immune responses and facilitate infection persistence. Targeting these immunosuppressive cells offers a promising therapeutic strategy for treating S. aureus biofilm-associated PJIs. Neddylation, a post-translational modification involving the conjugation of the ubiquitin-like protein NEDD8 to target proteins, regulates various cellular processes and may influence immune cell function during infection. Here, we investigated the role of neddylation in S. aureus biofilm-induced immunosuppression. We found that TAS4464, a selective neddylation inhibitor, markedly suppressed the expansion of MDSCs and M2 macrophages in bone marrow cells (BMCs) stimulated by S. aureus biofilm. TAS4464 also reduced the expression of inflammation-associated cytokines in these cells. Mechanistically, S. aureus biofilm upregulated key components of the neddylation pathway and markers of MDSCs and M2 macrophages in a dose-dependent manner; however, this upregulation is effectively counteracted by TAS4464. Furthermore, in a mouse model of PJI, TAS4464 treatment significantly reduced bone destruction and inflammation, which correlates with the inhibition of the neddylation pathway and a decrease in circulating MDSCs and M2 macrophages. These findings suggest that TAS4464 mitigates S. aureus biofilm-associated PJIs by disrupting the immunosuppressive microenvironment and highlight neddylation as a potential therapeutic target.

Keywords:  Biofilm; M2 macrophages; Myeloid-derived suppressor cells; Neddylation; Periprosthetic joint infection; Staphylococcus aureus

DOI:  https://doi.org/10.1016/j.biopha.2025.118622
Front Immunol. 2025 ;16 1607388

Gut microbiota: a promising new target in immune tolerance.

Nourah Almansour, Fatema Al-Rashed, Khubaib Choudhry, Hend Alqaderi, Sardar Sindhu, Fahd Al-Mulla, Rasheed Ahmad.

  Gut microbiota research has highlighted its pivotal role in human health and disease. Its composition is shaped by diet, genetics, age, and environmental factors. When the balance of these microbes is disrupted (dysbiosis), it can contribute to health problems like metabolic, inflammatory, and mental disorders. The microbiota supports digestion, fermentation, and vitamin production, which are essential for overall health. The gut microbiota has emerged as a critical modulator of immune function, with increasing evidence highlighting its role in establishing and maintaining immune tolerance. Despite significant advances in understanding the interactions between the gut microbiome and immune system, gaps remain in the literature regarding the specific mechanisms through which microbiota influences immune tolerance. This review aims to address these knowledge gaps by synthesizing current research on the microbiota impact on immune tolerance, emphasizing key factors such as microbial diversity, metabolic byproducts, and the microbiota interaction with immune cells, specifically focusing on the role of microbial tryptophan metabolites in PD-1/PD-L1 tolerance. We also highlight critical areas for future research, including the identification of microbial species or strains that can modulate immune tolerance, the influence of diet and environmental factors on microbiota composition, and the development of microbiota-based therapies. By bridging these gaps, this review seeks to provide a comprehensive understanding of the mechanistic role of microbiota immune tolerance and its potential as a novel therapeutic target for autoimmune and inflammatory diseases.

Keywords:  Treg; gut microbiota; immune modulation; immune tolerance; probiotics

DOI:  https://doi.org/10.3389/fimmu.2025.1607388
STAR Protoc. 2025 Oct 08. pii: S2666-1667(25)00540-4. [Epub ahead of print]6(4): 104134

Protocol for measuring cellular energetics through noncanonical amino acid tagging in human peripheral blood and murine tissue immune cells.

Frank Vrieling, Hendrik J P van der Zande, Manon Dumont, Rinke Stienstra.

  Cellular metabolism dictates immune cell function, yet we lack tools to functionally profile immunometabolism in low-yield, complex samples. We present a flow cytometry-based protocol for measuring cellular energetics through noncanonical amino acid tagging (CENCAT) in human peripheral blood and murine tissue immune cells. We describe steps for sample preparation, metabolic inhibition, protein synthesis analysis using click chemistry, immunophenotyping, and calculation of metabolic dependencies. For complete details on the use and execution of this protocol, please refer to Vrieling et al.1.

Keywords:  Cell Biology; Cell culture; Cell isolation; Flow Cytometry; Immunology; Metabolism; Molecular Biology; Molecular/Chemical Probes

DOI:  https://doi.org/10.1016/j.xpro.2025.104134
FEMS Microbiol Rev. 2025 Oct 11. pii: fuaf051. [Epub ahead of print]

Coenzyme A Metabolism: A Key Driver of Gut Microbiota Dynamics and Metabolic Profiles.

Johanna Böttcher, Ody C M Sibon, Sahar El Aidy.

  Coenzyme A (CoA) biosynthesis is a crucial process in living organisms, characterised by the production of conserved intermediates through enzyme-catalysed steps that vary across species. The synthesis of CoA entails several conversions, starting from pantothenate. Pantothenate is an essential vitamin in humans and is synthesised by certain bacterial species. Intermediates of the biosynthetic pathway have been shown to impact bacteria, especially in community settings such as the intestinal microbiota. Additionally, various diseases have been associated with impaired CoA and its downstream metabolic pathways in the gut microbiota, underscoring the significance of evaluating the current knowledge on how the CoA pathway influences the metabolic state of bacteria. This also highlights the importance of having standardised methodologies that can be employed to better understand their metabolism. In this review, we explore the current literature on bacterial CoA metabolism, with a particular focus on gut bacteria and the impact of CoA-related metabolites on bacterial composition, function and metabolism. Furthermore, we discuss previous and current methodologies employed to investigate CoA biosynthesis. Our goal is to provide valuable insights into the intricate relationship between CoA metabolism, gut microbiota and their implications for health and disease, offering a foundation for future research and therapeutic approaches.

Keywords:  Coenzyme A; bacteria; metabolic diseases; metabolism; microbiota; pantothenate

DOI:  https://doi.org/10.1093/femsre/fuaf051
Trends Immunol. 2025 Oct 06. pii: S1471-4906(25)00227-3. [Epub ahead of print]

A mother's touch: microbial guardians of early immune imprinting.

Melody Y Zeng, Julia A Brown.

  The evolution of the fetal immune system within the womb is a delicate balancing act: it is trained to not reject maternal antigens, while equipping itself with 'learned' immunity to survive and thrive in the outside world. In this opinion article, we propose that a deliberate maternal touch via immune and nutritional influences, orchestrated, in part, by microbiota-derived components, imprints the fetal immune system with the needed immune memory and epigenetic marks to navigate a far less nurturing outside world, including early microbial colonizers in the newborn's intestine, pathogens and irritants, and allergens in food. We redefine the hygiene hypothesis to include prenatal maternal microbial exposures, priming fetal immune development for long-term fitness and reduced inflammatory/autoimmune disease risk.

Keywords:  immune imprinting; maternal–fetal immune tolerance; metabolite; microbiota

DOI:  https://doi.org/10.1016/j.it.2025.09.008
Front Immunol. 2025 ;16 1676953

Ontogeny specification and epigenetic regulation of macrophage plasticity.

Han-Ying Huang, Xin-Nan Zheng, Lin Tian.

  Macrophages are ubiquitously distributed across tissues, playing pivotal roles in maintaining homeostasis under physiological conditions and modulating disease progression in pathological contexts. Although the classic M1/M2 classification of macrophage polarization provides a useful framework, it significantly oversimplifies the plasticity and heterogeneity of these cells. Recent advances that combine lineage tracing with multi-omic profiling have unveiled new insights into macrophage functional specification. In this mini-review, we examine how ontogeny, environmental cues, and genetic as well as epigenetic factors converge to drive macrophage plasticity through epigenetic reprogramming. Additionally, we highlight cutting-edge in situ profiling techniques that facilitate the study of macrophages within their native tissue microenvironment. A deeper understanding of macrophage plasticity promises to elucidate fundamental regulatory mechanisms and uncover novel therapeutic targets, paving the way for transformative disease treatments.

Keywords:  In situ profiling system; epigenetic reprogram; macrophage plasticity; niche factor; ontogeny

DOI:  https://doi.org/10.3389/fimmu.2025.1676953
Mol Hum Reprod. 2025 Oct 07. pii: gaaf048. [Epub ahead of print]

A Review on macrophage biology and its potential role in spontaneous abortion.

Xiaoxuan Zhao, Xinyi Ding, Qingnan Fan, Xintong Yao, Linxi Jin, Chaochao Sun, Huanxiao Ke, Qujia Yang, Xiaowei Chen, Saiya Ye, Yuepeng Jiang, Hongli Zhao.

  Spontaneous abortion (SA) is a challenging and frustrating obstetric complication. Immune dysregulation at the mother-fetal interface has long been recognized as a threat to pregnancy maintenance. Decidual macrophages are key gatekeepers for immune homeostasis at the mother-fetal interface, characterized by their heterogeneity and high plasticity. Abnormalities in their number, function, and phenotype are strongly associated with pregnancy loss. However, the specific regulation mechanisms remain elusive. Here, we outline the origin and identity of the endometrial macrophages and review their diverse changes in phenotypes and functions to pregnancy initiation. More importantly, we highlight the underlying mechanisms mediating aberrant changes in macrophage polarization and functions in the context of SA, involving epigenetic landscape dysregulation, metabolic reprogramming, and aberrant communication between macrophages and other component cells at the maternal-fetal interface. Altogether, these provide a clear framework for understanding the crucial roles and prospective therapeutic targets of macrophages in SA.

Keywords:  cell communication; epigenetic regulation; macrophages; maternal–fetal interface; metabolic reprogramming; organelle stress; polarization; spontaneous abortion

DOI:  https://doi.org/10.1093/molehr/gaaf048
Cell Mol Immunol. 2025 Oct 09.

Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.

Sagar R Dubey, Cynthia Turnbull, Abhimanu Pandey, Anyang Zhao, Melan Kurera, Radhwan Al-Zidan, Cheng Shen, Manjul Gautam, Shreya Mahajan, Poonam S Jadhav, Aritra Ghosh, Chinh Ngo, Si Ming Man.

  The inflammasome is an inflammatory signaling protein complex comprising a sensor protein, the adaptor protein ASC, and the cysteine protease caspase-1. Inflammasome sensor proteins are activated by microbial molecular patterns, endogenous self-derived damage signals, or exogenous environmental danger signals. Multiple inflammasomes that differ in their mechanisms of action and structural composition have been identified. The best characterized are the canonical NLRP1, NLRP3, NAIP-NLRC4, AIM2, and Pyrin inflammasomes and the noncanonical inflammasomes activated by caspase-4, caspase-5 or caspase-11. The lesser known inflammasomes are the NLRP6, NLRP7, NLRP9, NLRP10, NLRP12, CARD8, and MxA inflammasomes. Following inflammasome assembly, caspase-1 promotes the secretion of the proinflammatory cytokines IL-1β and IL-18, and pyroptosis is mediated by the membrane-disrupting proteins gasdermin D and ninjurin-1. These functional activities control innate and adaptive immune responses and the initiation, development, and progression of autoinflammation, cancer, infectious diseases, and neurodegenerative diseases. Understanding how inflammasomes respond to pathogens and sterile signals has refined our view of innate immunity and offered new therapeutic targets. In this review, we present a comprehensive overview of inflammasomes with an emphasis on the mechanistic principles that govern inflammasome formation. We also discuss the contributions of inflammasome activation to health and disease.

Keywords:  GSDMD; Infection; Interferons; LPS; NINJ1; Pattern-recognition receptors

DOI:  https://doi.org/10.1038/s41423-025-01354-y
Microb Physiol. 2025 Oct 03.

Microbiome: Friend or Friendly Foe.

Lakshmi B Reddy, Milton H Saier.

The human microbiome is a dynamic, polymicrobial ecosystem that plays an essential role in nutrition, immune development, barrier integrity, and host physiology, acting as a mutualistic partner under balanced conditions. However, its ecological complexity, genetic adaptability through horizontal gene transfer, and interactions with other prokaryotes as well as protozoan and metazoan parasites can transform commensals into pathobionts, resulting in weakened host's barriers, immunity declines with the progression of age, and community composition shifts toward dysbiosis. Factors such as diet, genetics, aging, immune-senescence, impaired autophagy, and environmental exposure, all influence this delicate balance, determining whether the microbiome remains protective or becomes an opportunistic source of inflammation and disease. This review focuses on the study of the intestinal microbiome in humans. Maintaining microbiome homeostasis is promoted through (a) dietary diversity, (b) limited antimicrobial use, (c) use of probiotics, (d) support for gut barrier function, and (e) healthy lifestyle improvements. These actions and considerations are critical to prevent the emergence of pathogenic states and preserving the microbiome's vital role in host health throughout life.

DOI: https://doi.org/10.1159/000548748
Eur J Immunol. 2025 Oct;55(10): e70068

Anti-SARS-CoV-2 Spike IgA2 Induces Inflammation by Human Macrophages.

Lynn Mes, Jennifer Veth, Julie Van Coillie, Jim B D Keijser, Elise Mantel, Richard van der Mast, Theo Rispens, Gestur Vidarsson, Marjolein van Egmond, Jeroen den Dunnen, Hung-Jen Chen.

  Severe COVID-19 is an immunological disorder characterized by a hyper-inflammatory reaction of the immune system. SARS-CoV-2 anti-spike antibodies of the IgG isotype are known to strongly contribute to this hyperinflammation by overactivation of alveolar macrophages. However, while the pathogenic function of IgG has been extensively studied, very little is known about the function of IgA, the most abundant immunoglobulin isotype in the airways. Although IgA is generally considered noninflammatory, in this study, we show that anti-spike IgA induces pronounced proinflammatory responses. We demonstrate that stimulation of macrophages with anti-spike IgA immune complexes in combination with a viral stimulus amplifies proinflammatory cytokine production. This IgA-induced inflammation is particularly driven by IgA2, the IgA subclass that is increased in the plasma of severely ill COVID-19 patients. We identified that IgA2-induced inflammation is predominantly dependent on FcαRI-Syk signaling. Mechanistically, IgA2-induced inflammation is linked to enhanced glycolysis and altered mitochondrial function, indicating subclass-specific immunometabolic reprogramming. Taken together, these data indicate a pathogenic role for IgA2 in severe COVID-19 and highlight its signaling cascades and metabolic pathways as potential druggable targets to counteract hyperinflammation in severe coronavirus infections, such as COVID-19, SARS, MERS, and potential future outbreaks.

Keywords:  COVID‐19; IgA; immunometabolism; inflammation; macrophage

DOI:  https://doi.org/10.1002/eji.70068
Mol Biol Rep. 2025 Oct 06. 52(1): 985

Interspecies signaling can sensitize intrinsically resistant Streptococcus pyogenes to colistin.

Amrita Bhagwat, Hardik D Rathod, Sunil D Saroj.



Keywords:  Antibiotic resistance; Cell surface charge; Colistin; Gram-positive pathogens; Oxo-C12-HSL; Quorum sensing.

DOI:  https://doi.org/10.1007/s11033-025-11103-z
Mucosal Immunol. 2025 Oct 09. pii: S1933-0219(25)00106-0. [Epub ahead of print]

Group 3 innate lymphoid cell-derived CSF2 tunes homeostasis of tissue macrophages and neutrophils.

S L Tai, F Wong, K Burrows, L Ngai, P Chiaranunt, L Savo, M Jeong, Z Y Chen, L Hao, F Lau, J Wang, A Mortha.

  Group 3 innate lymphoid cells (ILC3) are tissue-resident lymphocytes that contribute to tissue and immune homeostasis. Alterations in ILC3 development or deficiency in their effector functions have beneficial and detrimental outcomes on chronic inflammation, host defense and barrier integrity. Although research has progressed in understanding these cells, multiple aspects of their biology remain poorly understood and difficult to investigate using current available techniques. This is primarily due to the lack of accessible and suitable tools to isolate, manipulate, and investigate ILC3 in vitro and in vivo. Here, we report an economical system to investigate the biology of ILC3 in vitro and in vivo, using the previously described ILC3 cell line MNK3. We demonstrate that MNK3 cells are a relevant model for in vivo investigations into the biology of ILC3. We describe and validate a straightforward strategy to genetically modify MNK3 cells ex vivo to dissect the role of their effector functions in the steady state or during inflammation and infection. Using this system, we identified a previously underappreciated role for ILC3-derived Colony Stimulating Factor 2 (CSF2) in regulating splenic and hepatic myeloid cell homeostasis. Collectively, we present a system to investigate the biology of ILC3 that is suitable, and accessible to a wider audience in academic research.

Keywords:  Citrobacter rodentium; Granulocyte macrophage colony stimulating factor; Group 3 Innate Lymphoid Cell; Indomethacin; Liver; MNK3; Macrophage; Mouse Model; Small intestine

DOI:  https://doi.org/10.1016/j.mucimm.2025.10.004
J Pineal Res. 2025 Nov;77(6): e70087

Melatonin Confers Protection Against Multidrug-Resistant Bacterial Infections in Aged Mice Via Microbiota-Derived Butyrate.

Wenjiao Xu, Jiaqi Bo, Liyan Jia, Kui Zhu, Qingfeng Luo.

  Aging is associated with increased susceptibility to bacterial infections, particularly multidrug-resistant (MDR) strains, which often result in antibiotic treatment failure and high mortality rates in the elderly. However, effective preventive and therapeutic strategies remain limited. Herein, we showed that aged mice exhibited higher susceptibility to colistin-resistant Salmonella enterica serotype Typhimurium and methicillin-resistant Staphylococcus aureus compared to young mice. Notably, pre-supplementation with melatonin, a hormone markedly reduced in the aging gut, effectively restricted MDR bacterial infections in aged mice by enhancing microbial colonization resistance. Mechanistically, melatonin-induced alterations in the gut microbiota, particularly the enrichment of butyrate-producing bacteria including Faecalibaculum, Muribaculaceae, and Ruminococcus, played a pivotal role in enhancing resistance to pathogenic bacteria. Elevated gut butyrate levels following melatonin pre-supplementation not only preserved intestinal barrier integrity and mitigated inflammaging, but also directly inhibited pathogenic bacterial growth by disrupting intracellular pH homeostasis, leading to proton motive force dissipation and metabolic disturbances. These findings underscore melatonin and its metabolite, butyrate, as promising candidates for the prevention of MDR bacterial infections in the aging population.

Keywords:  aging; butyrate; colonization resistance; melatonin; multidrug‐resistant bacterial infection

DOI:  https://doi.org/10.1111/jpi.70087
J Nat Med. 2025 Oct 06.

Calycosin ameliorates inflammation and M1 macrophage polarization via Spon2 in LPS-triggered MH-S alveolar macrophages.

Gaoyan Chen, Xiaogang Li, Jingyi Zhang, Jiangli Ding, Yongchao Jiang, Rui Pan.

  Acute lung injury (ALI) remains a critical inflammatory condition with limited therapeutic interventions. This study explores the anti-inflammatory potential of calycosin (CAL), a bioactive flavonoid, in lipopolysaccharide (LPS)-induced MH-S alveolar macrophages cell line, with particular focus on macrophage polarization mechanisms. Through CCK-8 cytotoxicity assessment and subsequent experimental grouping (control, LPS, and LPS + CAL), we demonstrated CAL's ability to significantly suppress LPS-triggered inflammatory mediators including IL-1β, TNF-α, and IL-6 at both transcriptional and protein levels. Flow cytometric analysis revealed CAL's dual regulatory effect on macrophage polarization markers, downregulating M1-associated CD86 while enhancing M2-related CD206 expression. Transcriptomic profiling identified 5,944 differentially expressed genes in LPS-stimulated cells enriched in TNF signaling pathways, while CAL treatment specifically modulated 83 genes predominantly involved in TGF-β signaling. Mechanistic investigations identified Spon2 as a critical mediator, where CAL-induced Spon2 downregulation attenuated inflammation and promoted M2 polarization, effects corroborated through Spon2-shRNA knockdown and overexpression experiments. Notably, we newly demonstrate that Spon2 overexpression abolishes CAL-mediated suppression of TNF-α and activation of TGF-β/Smad2 signaling. These findings collectively establish CAL as a promising therapeutic candidate for ALI through its Spon2-mediated modulation of macrophage polarization dynamics.

Keywords:  Calycosin; Inflammatory response; MH-S alveolar macrophages; Macrophage activity; Spon2

DOI:  https://doi.org/10.1007/s11418-025-01944-0
Front Immunol. 2025 ;16 1675677

Microbial metabolites and their influence on the tumor microenvironment.

Huanglin Duan, Baisheng Xu, Peiyue Luo, Tao Chen, Jun Zou.

  While tumor immunotherapy has achieved remarkable progress in many hematological malignancies, its efficacy remains limited by key challenges, including the immunosuppressive microenvironment of solid tumors, metabolic abnormalities, and drug resistance. As a central mechanism underlying impaired immune function, metabolic reprogramming of immune cells has emerged as a pivotal focus for unraveling tumor immune evasion and therapeutic resistance. Advances in metagenomics have highlighted the significance of the human commensal microbiome as a 'second genome.' Microbial metabolites, whether circulating systemically or accumulating locally, serve as key messengers linking the microbiota to tumor immunometabolism. This review comprehensively examines the regulatory roles and metabolic mechanisms through which microbial metabolites-including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and lipopolysaccharides (LPS)-modulate tumor immunity and immunotherapeutic responses via immune cell metabolism. These metabolites shape the tumor immune microenvironment and influence immunotherapeutic efficacy by reprogramming immune cell metabolic and biosynthetic pathways. This review underscores the central regulatory role of microbial metabolites as the 'second genome' in tumor immunometabolism, offering a theoretical foundation and potential targets to elucidate mechanisms of immunotherapeutic resistance and advance microbiota metabolism-based precision interventions.

Keywords:  immunometabolism; immunotherapy; microbial metabolites; tumor immunity; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2025.1675677
Nat Rev Bioeng. 2024 Sep;2(9): 733-751

Engineered polysaccharides for controlling innate and adaptive immune responses.

Jutaek Nam, April Kim, Kidong Kim, Jeong Hyun Moon, Juwon Baig, May Phoo, James J Moon, Sejin Son.

Therapeutic interventions can be designed by exploiting the immune system's ability to initiate specific responses to various stimuli. However, specific T cell activation, which is a key target for vaccines and immunotherapies, remains challenging. Polysaccharides derived from microbial cell walls are promising immunomodulators that interact with pathogen-recognition receptors (PRRs) on dendritic cells and macrophages, triggering robust immune responses for modulating T cell function and activating effector or regulatory pathways. In this Review, we discuss the role of polysaccharides as pathogen-associated molecular patterns (PAMPs) recognized by PRRs and their immunomodulatory potential for biomedical applications. We examine the engineering aspects of polysaccharides, investigating their potential in vaccine, immunoadjuvant, immune-modulation and drug-delivery applications and highlighting their immune-activating or immune-regulatory functions. We also explore how trained immunity can be induced by polysaccharides to trigger immune responsiveness upon re-encountering pathogens. By leveraging materials engineering principles, polysaccharides can offer a platform for effective vaccines and immunotherapies against autoimmune and other diseases.

DOI: https://doi.org/10.1038/s44222-024-00193-2
Nature. 2025 Oct 07.

The rise of 'nightmare bacteria': antimicrobial resistance in five charts.

Katie Kavanagh.



Keywords:  Antibiotics; Drug discovery; Infection

DOI:  https://doi.org/10.1038/d41586-025-03218-x
J Allergy Clin Immunol. 2025 Oct 08. pii: S0091-6749(25)01022-X. [Epub ahead of print]

Barrier dysfunction in nasal epithelium contributes to persistent inflammation in long COVID.

P4O2 consortium

   RATIONALE AND OBJECTIVES: Long COVID (LC) is characterized by persistent symptoms associated with chronic inflammation and immune dysregulation, but the local tissue mechanisms driving these processes remain poorly understood. Given that the nasal epithelium is the primary entry and infection site for SARS-CoV-2, we aimed to investigate its role in LC and its potential contribution to systemic immune activation.
METHODS: We analyzed nasal epithelial samples and peripheral blood from participants in the Precision Medicine for more Oxygen (P4O2) COVID-19 cohort, post-COVID individuals and healthy controls. We assessed epithelial barrier integrity, evaluated wound healing and explored cytokine profiles. Transcriptomic analysis was performed via RNA-sequencing. Blood innate lymphoid cells (ILCs) were phenotyped by flow cytometry and stimulated in vitro for functional assays.
RESULTS: Among a subgroup of LC patients, nasal epithelial cells showed impaired barrier function, reduced expression of ZO-1 and occludin and exaggerated sensitivity to viral triggers. Despite faster wound closure, the epithelial repair was reduced. The LC nasal epithelium exhibited increased cytokine production, including IL-1β and transcriptomic signatures of inflammation, including upregulation of interferon pathways. Furthermore, we found that TFs ATF3 and EGR1 were downregulated in LC. Elevated IL-1β levels in nasal epithelium promoted ILC activation and plasticity towards IFN-γ-producing ILCs in blood.
CONCLUSION: While multiple organ systems are implicated in LC, our findings identified nasal epithelial dysfunction in a subgroup of LC patients and chronic activation as potential contributors to systemic immune dysregulation. The IL-1β-IFN-γ axis represents a novel targetable pathway that may support precision therapies for long COVID.

Keywords:  Long COVID; epithelial barrier dysfunction; epithelial-immune crosstalk; post-viral condition; precision medicine

DOI:  https://doi.org/10.1016/j.jaci.2025.09.024
Curr Opin Immunol. 2025 Oct 09. pii: S0952-7915(25)00153-0. [Epub ahead of print]97 102677

Layers of defense: protection from respiratory viruses by epithelial-intrinsic immunity.

Ellen F Foxman.

A central challenge in defending mucosal barriers is protecting against pathogens while also limiting excessive inflammation. Respiratory viruses are a prime example - respiratory viruses present a threat to their target cells, the epithelial cells that line the airways, but excessive leukocyte recruitment to fight the infection can lead to inflammation and respiratory distress. This review focuses on how epithelial-intrinsic defenses contribute to achieving a balanced antiviral response by adding 'layers of defense' that engage in sequence to control infections. Layers include: (1) secreting a defensive extracellular barrier, (2) directly blocking viral replication through cell-intrinsic effector mechanisms, (3) amplifying cell-intrinsic defenses within the epithelium through Type III interferons and other epithelial-specific mechanisms, and (4) coordinating leukocyte recruitment and activation. Recent findings in humans and organoid models support the idea that the 'layers of defense' created by epithelial-intrinsic mechanisms frequently and successfully counteract respiratory virus infections and limit their health impact.

DOI: https://doi.org/10.1016/j.coi.2025.102677
Respir Res. 2025 Oct 08. 26(1): 285

Monocyte-derived macrophages support alveolar regeneration via oncostatin M post-H1N1 infection during the recovery phase.

Xiao Shang, Ju Jia, Jiapei Yu, Shumei Zou, Zeyi Wang, Jiuyang Xu, Hui Li, Bin Cao.



Keywords:  Alveolar regeneration; Monocyte-derived macrophages; Oncostatin M; ScRNA-seq

DOI:  https://doi.org/10.1186/s12931-025-03359-7
Sci Bull (Beijing). 2025 Sep 19. pii: S2095-9273(25)00967-3. [Epub ahead of print]

Microbiota-derived metabolites in the epigenetic regulation of the host.

Junwen Lei, Xiaoyi Wang, Xingyin Liu.

  The gut microbiota plays a crucial role in maintaining host health and modulating disease progression. Microbiota-derived metabolites (MDMs) form a complex and diverse repertoire of molecules that interact uniquely with the host and regulate epigenetics. In this review, we provide a comprehensive overview by examining the current evidence on how MDMs reshape host epigenetic landscape, and we highlight the innovative concept of the "MDMs-epigenetic (MDME) axis" as a potential framework for exploring and understanding microbiota-host interactions. Next, we underscore the significance of the MDME axis in driving mechanistic studies and elucidating the underlying biological processes and pathophysiological pathways involved in various diseases. Finally, we discuss the impact of MDMs on epigenetic landscapes, outline future directions, and highlight their pivotal role in both mechanistic investigation and the development of clinical therapies.

Keywords:  Epigenetics; Host–microbiota interaction; Microbiota; Microbiota-derived metabolites (MDMs)

DOI:  https://doi.org/10.1016/j.scib.2025.09.030