bims-bac4me 2025-03-30 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2025–03–30
37 papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Metabolic Adaptations Driving Innate Immune Memory: Mechanisms and Therapeutic Implications.
Aminobisphosphonates Potentiate Non-Specific Immunological Memory.
Establishment and validation of red fox (vulpes vulpes) airway epithelial cell cultures at the air-liquid-interface.
Staphylococcus aureus reprograms CASP8 (caspase 8) signaling to evade cell death and Xenophagy.
Modulation of Macrophages TLR4-Mediated Transcriptional Response by Lacticaseibacillus rhamnosus CRL1505 and Lactiplantibacillus plantarum CRL1506.
BCG-derived acellular membrane vesicles elicit antimycobacterial immunity and innate immune memory.
The microbial metabolite delta-valerobetaine strengthens the gut epithelial barrier.
RIG-I and cGAS mediate antimicrobial and inflammatory responses of primary osteoblasts and osteoclasts to Staphylococcus aureus.
Closing in on epithelial barrier dysfunction in chronic rhinosinusitis.
Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.
A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection.
Effect of Human Macrophage Conditioned Media on TGF-β-Induced Differentiation of Lung Fibroblasts.
Darutoside promotes skin wound healing via regulating macrophage polarization.
Lipid metabolism in ferroptosis: mechanistic insights and therapeutic potential.
LL37 complexed to double-stranded RNA induces RIG-I-like receptor signalling and Gasdermin E activation facilitating IL-36γ release from keratinocytes.
Mutual Interactions Between Microbiota and the Human Immune System During the First 1000 Days of Life.
New antibiotic that kills drug-resistant bacteria discovered in technician's garden.
Proinflammatory cytokines sensitise mesenchymal stromal cells to apoptosis.
ImmGenMaps, an open-source cartography of the immune system.
For Better or Worse: Type I Interferon Responses in Bacterial Infection.
The role of microbial succinate in the pathophysiology of inflammatory bowel disease: mechanisms and therapeutic potential.
Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation.
Lactylation: A Novel Epigenetic Regulator of Cellular Senescence.
Interleukin 8 Molecular Interplay in Allergic Rhinitis and Chronic Rhinosinusitis with Nasal Polyps: A Scoping Review.
Toll-like Receptor Activation Remodels the Polyamine and Tryptophan Metabolism in Porcine Macrophages.
Caspase-1 is critical for mice in the defense against Streptococcus equi subsp. zooepidemicus infection by promoting macrophage phagocytosis.
Bifidobacterium breve HH079 alleviates early-life antibiotic-exposed colon dysbiosis in mice by restoring the gut microbiota and gut barrier function.
Recent Advances in Nose and Lung Organoid Models for Respiratory Viral Research.
Activated Notch1 promotes macrophage polarization and exacerbates sepsis-induced acute lung injury via β-catenin/NF-κB signaling.
Advanced Membrane Simulations in Probiotics and Gut Microbiome Interaction Research: The Current Trends and Insights.
Refining Unfavorable Vaginal Microbial Community in Infertile Women Subjected to Precision Probiotic Intervention: An Exploratory Single-Arm, Prospective, Open-Label, Interventional Study.
Functional efficacy of Enterococcus faecium HN4 and Lactobacillus delbrueckii HN5 strains isolated from human milk.
Human microbiome acquisition and transmission.
Nutritional Stress Leads to Persistence and Persister-like Growth in Staphylococcus aureus.
Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.
Dual faces of itaconate and its derivatives: exploring diverse biological functions in immunity and infectious diseases.
Versatility of gasdermin D beyond pyroptosis.

J Leukoc Biol. 2025 Mar 26. pii: qiaf037. [Epub ahead of print]

Metabolic Adaptations Driving Innate Immune Memory: Mechanisms and Therapeutic Implications.

Dan Hao, Margaret A McBride, Julia K Bohannon, Antonio Hernandez, Benjamin Klein, David L Williams, Edward R Sherwood.

  Immune memory is a hallmark of the adaptive immune system. However, recent research reveals that innate immune cells also retain memory of prior pathogen exposure that prompts enhanced responses to subsequent infections. This phenomenon is termed "innate immune memory" or "trained immunity." Notably, remodeling of cellular metabolism, which closely links to epigenetic reprogramming, is a prominent feature of innate immune memory. Adaptations in glycolysis, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), glutaminolysis, and lipid synthesis pathways are critical for establishing innate immune memory. This review provides an overview of the current understanding of how metabolic adaptations drive innate immune memory. This understanding is fundamental to understanding innate immune system functions and advancing therapies against infectious diseases.

Keywords:  Innate immune memory; immune therapy; metabolism; trained immunity

DOI:  https://doi.org/10.1093/jleuko/qiaf037
Bull Exp Biol Med. 2025 Mar 25.

Aminobisphosphonates Potentiate Non-Specific Immunological Memory.

Y Sh Schwartz, O V Semenova, A V Salmin.

  Innate immune cells have the ability to acquire non-specific immunological memory (NIM), which provides resistance to a variety of bacterial and viral infections. Experiments in vitro and in vivo have verified the hypothesis that the farnesyl pyrophosphate synthase inhibitor (aminobisphosphonates) can potentiate BCG-induced NIM. The aminobisphosphonate zoledronate induced the NIM phenotype in human monocyte cultures and provided nonspecific protection against staphylococcal infection in mice. Additionally, zoledronate significantly enhanced BCG-induced NIM, resulting in a synergistic protective effect. The phenomenon of potentiation of NIM/anti-infectious resistance discovered by us can form the basis for designing powerful universal vaccines of a new type.

Keywords:  BCG; Staphylococcus aureus; non-specific immunological memory; trained innate immunity; zoledronate

DOI:  https://doi.org/10.1007/s10517-025-06350-w
Sci Rep. 2025 Mar 22. 15(1): 9883

Establishment and validation of red fox (vulpes vulpes) airway epithelial cell cultures at the air-liquid-interface.

Andreas W Oehm, Blandina I Oliveira Esteves, Udo Hetzel, Marco P Alves, Manuela Schnyder.

  The airway epithelium represents a central barrier against pathogens and toxins while playing a crucial role in modulating the immune response within the upper respiratory tract. Understanding these mechanisms is particularly relevant for red foxes (Vulpes vulpes), which serve as reservoirs for various zoonotic pathogens like rabies or the fox tapeworm (Echinococcus multilocularis). The study aimed to develop, establish, and validate an air-liquid interface (ALI) organoid model of the fox respiratory tract using primary airway epithelial cells isolated from the tracheas and main bronchi of hunted red foxes. The resulting ALI cultures exhibited a structurally differentiated, pseudostratified epithelium, characterised by ciliated cells, mucus secretion, and tight junctions, as confirmed through histological and immunohistochemical analysis. Functional assessments using a paracellular permeability assay and measurement of transepithelial electrical resistance, demonstrated a tight epithelial barrier. The potential of model's utility for studying innate immune responses to respiratory infections was validated by exposing the cultures to lipopolysaccharide, phorbol-12-myristate-13-acetate and ionomycin, and nematode somatic antigens. Quantitative PCR revealed notable changes in the expression of pro-inflammatory cytokines TNF and IL-33. This in vitro model represents a significant advancement in respiratory research for non-classical species that may act as important wildlife reservoirs for a range of zoonotic pathogens.

Keywords:   In vitro model; Fox; Host-pathogen interaction; Respiratory tract; Wildlife reservoir

DOI:  https://doi.org/10.1038/s41598-025-94033-x
Autophagy. 2025 Mar 26.

Staphylococcus aureus reprograms CASP8 (caspase 8) signaling to evade cell death and Xenophagy.

Yi-Tian Ying, Jing Yang, Hui-Wen Ye, Mei-Yi Chen, Xia Liu, Wei Chen, Jin-Xin Xu, Xun Tan.

  Regulated cell death and xenophagy constitute fundamental cellular mechanisms against invading microorganisms. Staphylococcus aureus, a notorious pathogen, can invade and persist within host cells for extended periods. Here, we describe a novel mechanism by which S. aureus subverts these host defenses through the manipulation of the CASP8 (caspase 8) signaling pathway. Upon invasion, S. aureus triggers the assembly of a RIPK3 (receptor interacting serine/threonine kinase 3) complex to induce CASP8 autoprocessing. However, the bacterium inhibits CUL3 (cullin 3)-dependent K63-linked ubiquitination, leading to an atypical activation of CASP8. This non-canonical activation does not initiate the CASP8-CASP3 cascade but instead suppresses RIPK3-dependent necroptosis, a regulated cell death pathway typically activated when apoptosis fails. The resulting non-apoptotic, cleaved CASP8 redirects its enzymatic activity toward cleaving SQSTM1/p62, a selective macroautophagy/autophagy receptor, thus enabling S. aureus to evade antimicrobial xenophagy. The results of this study suggest that S. aureus reprograms the CASP8 signaling pathway from inducing cell death to preserving cell survival and inhibiting xenophagy, a critical strategy that supports its stealthy replication and persistence within host cells.

Keywords:  Apoptosis; RIPK1; RIPK3; SQSTM1/p62; autophagy; necroptosis

DOI:  https://doi.org/10.1080/15548627.2025.2483887
Int J Mol Sci. 2025 Mar 17. pii: 2688. [Epub ahead of print]26(6):

Modulation of Macrophages TLR4-Mediated Transcriptional Response by Lacticaseibacillus rhamnosus CRL1505 and Lactiplantibacillus plantarum CRL1506.

Masahiko Suzuki, Ayelen Baillo, Leonardo Albarracin, Mariano Elean, Rodrigo Serda, Yoshihito Suda, Fu Namai, Keita Nishiyama, Haruki Kitazawa, Julio Villena.

  Lacticaseibacillus rhamnosus CRL1505 and Lactiplantibacillus plantarum CRL1506 increase the resistance of mice to Gram-negative pathogens infections. In this work, we advanced the characterization of the CRL1505 and CRL1506 immunomodulatory properties by evaluating their effect on the Toll-like receptor 4 (TLR4)-triggered immune response in macrophages. We performed experiments in murine RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) to evaluate the transcriptomic changes induced by lactobacilli. These in vitro experiments were complemented with in vivo studies in mice to determine the effect of CRL1505 and CRL1506 strains on Peyer's patches and peritoneal macrophages. Microarray transcriptomic studies and qPCR confirmation showed that the CRL1505 and CRL1506 strains modulated the expression of inflammatory cytokines and chemokines as well as adhesion molecules in LPS-challenged RAW macrophages, making the effect of L. rhamnosus CRL1505 more remarkable. Lactobacilli also modulate regulatory factors in macrophages. L. plantarum CRL1506 increased il10 and socs2 while L. rhamnosus CRL1505 upregulated il27, socs1, and socs3 in RAW cells, indicating a strain-specific effect. However, in vivo, both strains induced similar effects. Peyer's patches and peritoneal macrophages from mice treated with lactobacilli produced higher levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and colony stimulating factor (CSF)-3 after LPS stimulation. This effect would allow improved protection against pathogens. In addition, both lactobacilli equally modulated socs1 and socs2 expressions and IL-10 and IL-27 production in Peyer's patches macrophages and socs3 and IL-10 in peritoneal cells. Furthermore, lactobacilli reduced the production of IL-1β, IL-12, CSF2, C-C motif chemokine ligand (CCL)-2, and CCL8 in LPS-challenged macrophages. This differential modulation of regulatory and inflammatory factors would allow minimal inflammatory-mediated tissue damage during the generation of the innate immune response. This work provides evidence that L. rhamnosus CRL1505 and L. plantarum CRL1506 modulate macrophages' TLR4-mediated immunotranscriptomic response, helping to improve protection against Gram-negative bacterial infections.

Keywords:  L. plantarum CRL1506; L. rhamnosus CRL1505; TLR4; macrophages; probiotics; transcriptomics

DOI:  https://doi.org/10.3390/ijms26062688
Front Immunol. 2025 ;16 1534615

BCG-derived acellular membrane vesicles elicit antimycobacterial immunity and innate immune memory.

Takehiro Yamaguchi, Noriaki Samukawa, Sohkichi Matsumoto, Masayuki Shiota, Masaki Matsumoto, Ryoma Nakao, Satoru Hirayama, Yutaka Yoshida, Akihito Nishiyama, Yuriko Ozeki, Shuhei Tomita.

  Tuberculosis (TB) is one of the leading causes of death due to infectious disease. The sole established vaccine against TB is the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine. However, owing to the lack of durable immunity with the BCG vaccine and its risk of infection, safer vaccines that can also be used as boosters are needed. Here, we examined whether membrane vesicles (MVs) from BCG (BCG-MVs) isolated from BCG statically cultured in nutrient-restricted Sauton's medium (s-MVs) and from BCG planktonically cultured in nutrient-rich medium commonly used in the laboratory (p-MVs) could be used as novel TB vaccines. MVs are extracellular vesicles produced by various bacteria, including mycobacteria. Differences in the culture conditions affected the morphology, contents, immunostimulatory activity and immunogenicity of BCG-MVs. s-MVs presented greater immunostimulatory activity than p-MVs via the induction of TLR2 signaling. Mouse immunization experiments revealed that s-MVs, but not p-MVs, induced mycobacterial humoral and mucosal immunity, especially when administered in combination with adjuvants. In a BCG challenge experiment using BCG Tokyo type I carrying pMV361-Km, subcutaneous vaccination with s-MVs reduced the bacterial burden in the mouse lung to a level similar to that after intradermal vaccination with live BCG. Furthermore, the administration of s-MVs induced a significant lipopolysaccharide-induced proinflammatory response in macrophages in vitro. These results indicate that BCG-MVs obtained from static culture in Sauton's medium induce not only humoral immunity against mycobacteria but also trained immunity, which can allow the clearance of infectious agents other than mycobacteria. Together, these findings highlight the immunological properties of BCG-MVs and the availability of acellular TB vaccines that confer broad protection against various infectious diseases.

Keywords:  BCG; acellular vaccines; membrane vesicles (MVs); trained immunity; tuberculosis

DOI:  https://doi.org/10.3389/fimmu.2025.1534615
Am J Pathol. 2025 Mar 21. pii: S0002-9440(25)00079-3. [Epub ahead of print]

The microbial metabolite delta-valerobetaine strengthens the gut epithelial barrier.

Lauren C Askew, C Anthony Gacasan, Maria E Barbian, Jaclyn Weinberg, Liping Luo, Brian S Robinson, Dean P Jones, Christopher D Scharer, Rheinallt M Jones.

  Metabolic processes within gut microbes generate bioactive metabolites that impact intestinal epithelial barrier function. Using gnotobiotic mice and mass spectrometry-based metabolomics, we identified novel metabolites in host tissues that are of microbial origin. Of those detected, we showed that the gut microbe generated metabolite δ-valerobetaine (δ-VB) is a potent inhibitor of L-carnitine biosynthesis and a modulator of fatty acid oxidation by mitochondria in liver cells. In the current study, we assessed the bioactivity of δ-VB towards gut epithelial barrier function. Germ-free mice are devoid of δ-VB, and we show that administration of δ-VB to germ-free mice also induces the enrichment of transcript sets associated with gut mitochondrial respiration and fatty acid oxidation in colonic tissue. Furthermore, we detected that δ-VB induces the differential expression of genes that function in barrier function in germ-free and conventionally raised mice. Functionally, δ-VB decreased gut barrier permeability and augmented wound healing in cultured gut epithelial cells, and elicited cytoprotective and pro-restitutive effects in a mouse model of colonic injury. We conclude that the microbial derived metabolite δ-VB is a modulator of gut epithelium function, and thus is a molecular target to potentially manage microbiome-host dysbiosis in intestinal health and disease.

Keywords:  5-aminovaleric acid betaine; Claudins; Colon; Microbiome; metabolites; δ-valerobetaine (δ-VB)

DOI:  https://doi.org/10.1016/j.ajpath.2025.02.007
mBio. 2025 Mar 26. e0397124

RIG-I and cGAS mediate antimicrobial and inflammatory responses of primary osteoblasts and osteoclasts to Staphylococcus aureus.

Erin L Mills, Samantha R Suptela, Mary-Kate Key, Ian Marriott, M Brittany Johnson.

  Staphylococcus aureus is the primary causative agent of osteomyelitis, and it is now apparent that osteoblasts and osteoclasts play a significant role in the pathogenesis of such infections. Their responses can either be protective or exacerbate inflammatory bone loss and are mediated by the recognition of microbial motifs by various pattern recognition receptors. We have recently reported that osteoblasts can respond to S. aureus challenge with the production of the type I interferon, interferon-beta, which can reduce the number of viable bacteria harbored within infected cells. In the present study, we demonstrate that S. aureus viability and internalization are necessary for maximal inflammatory cytokine and type I interferon responses of primary bone cells to this pathogen. Importantly, we show that primary murine and human bone cells constitutively express the cytosolic nucleic acid sensors, retinoic acid inducible gene I (RIG-I) and cyclic GMP-AMP synthase (cGAS), and demonstrate that such expression is markedly upregulated following S. aureus infection. The functional status of RIG-I and cGAS in osteoblasts and osteoclasts was confirmed by showing that specific ligands for each can also elevate their expression and induce cytokine responses. We have verified the specificity of such responses using siRNA knockdown or pharmacological inhibition and used these approaches to demonstrate that both sensors play a pivotal role in bone cell responses to infection with clinically relevant strains of S. aureus. Finally, we have begun to establish the biological significance of RIG-I- and cGAS-mediated bone cell responses with the demonstration that their attenuation increases S. aureus burden in infected cells, suggesting a potentially protective role for these sensors in osteomyelitis.IMPORTANCEStaphylococcal osteomyelitis is a severe infection that is often recalcitrant to current treatment strategies. We and others have demonstrated that resident bone cells are not merely passive victims but can respond to bacteria with the production of an array of immune mediators, including type I interferons, that could serve to limit such infections. Here, we demonstrate the functional expression of two cytosolic nucleic acid sensors, retinoic acid inducible gene I and cyclic GMP-AMP synthase, in primary murine and human osteoblasts and murine osteoclasts. We show that these pattern recognition receptors mediate potentially protective bone cell type I interferon responses to Staphylococcus aureus infection.

Keywords:  RIG-I; Staphylococcus aureus; cGAS; cytokines; osteoblasts; osteoclasts; type I interferon

DOI:  https://doi.org/10.1128/mbio.03971-24
J Allergy Clin Immunol. 2025 Mar 20. pii: S0091-6749(25)00323-9. [Epub ahead of print]

Closing in on epithelial barrier dysfunction in chronic rhinosinusitis.

Nora A Barrett.



Keywords:  Epithelial cell; airway stem cell; basal cell; chronic rhinosinusitis with nasal polyps; epithelial remodeling

DOI:  https://doi.org/10.1016/j.jaci.2025.02.039
Mol Syst Biol. 2025 Mar 25.

Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.

Alexander Simonis, Sebastian J Theobald, Anna E Koch, Ram Mummadavarapu, Julie M Mudler, Andromachi Pouikli, Ulrike Göbel, Richard Acton, Sandra Winter, Alexandra Albus, Dmitriy Holzmann, Marie-Christine Albert, Michael Hallek, Henning Walczak, Thomas Ulas, Manuel Koch, Peter Tessarz, Robert Hänsel-Hertsch, Jan Rybniker.

  Immune memory plays a critical role in the development of durable antimicrobial immune responses. How precisely mRNA vaccines train innate immune cells to shape protective host defense mechanisms remains unknown. Here we show that SARS-CoV-2 mRNA vaccination significantly establishes histone H3 lysine 27 acetylation (H3K27ac) at promoters of human monocyte-derived macrophages, suggesting epigenetic memory. However, we found that two consecutive vaccinations were required for the persistence of H3K27ac, which matched with pro-inflammatory innate immune-associated transcriptional changes and antigen-mediated cytokine secretion. H3K27ac at promoter regions were preserved for six months and a single mRNA booster vaccine potently restored their levels and release of macrophage-derived cytokines. Interestingly, we found that H3K27ac at promoters is enriched for G-quadruplex DNA secondary structure-forming sequences in macrophage-derived nucleosome-depleted regions, linking epigenetic memory to nucleic acid structure. Collectively, these findings reveal that mRNA vaccines induce a highly dynamic and persistent training of innate immune cells enabling a sustained pro-inflammatory immune response.

Keywords:  Epigenetic Memory; G-quadruplex; H3K27ac; SARS-Cov-2 mRNA Vaccination; Trained Innate Immunity

DOI:  https://doi.org/10.1038/s44320-025-00093-6
EMBO J. 2025 Mar 24.

A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection.

Hui Wen Yeap, Ghin Ray Goh, Safwah Nasuha Rosli, Hai Shin Pung, Cristina Giogha, Vik Ven Eng, Jaclyn S Pearson, Elizabeth L Hartland, Kaiwen W Chen.

  Innate immune signalling and cell death pathways are highly interconnected processes involving receptor-interacting protein kinases (RIPKs) as mediators of potent anti-microbial responses. However, these processes are often antagonised by bacterial type III secretion system (T3SS) effectors, and the cellular mechanisms by which the host retaliates are not completely understood. Here, we demonstrate that during Citrobacter rodentium infection, murine macrophages and colonic epithelial cells exhibit RIPK1 kinase-dependent caspase-8 activation to counteract NleE effector-mediated suppression of pro-inflammatory signalling. While C. rodentium injects into the host cells a second effector, NleB, to block caspase-8 signalling, macrophages respond by triggering RIPK3-mediated necroptosis, whereupon a third T3SS effector, EspL, acts to inactivate necroptosis. We further show that NleB and EspL collaborate to suppress caspase-8 and NLRP3 inflammasome activation in macrophages. Our findings suggest that C. rodentium has evolved to express a complex network of effectors as an adaptation to the importance of cell death for anti-bacterial defence in the host-pathogen arms race.

Keywords:  Apoptosis; Caspase-8; Infection; Necroptosis; Pyroptosis

DOI:  https://doi.org/10.1038/s44318-025-00412-5
Bull Exp Biol Med. 2025 Mar 26.

Effect of Human Macrophage Conditioned Media on TGF-β-Induced Differentiation of Lung Fibroblasts.

A A Maksimova, E Ya Shevela, M A Tikhonova, I M Rashchupkin, A A Ostanin, E R Chernykh.

  We studied the ability of human macrophage conditioned media to inhibit differentiation of lung fibroblasts in vitro. The results showed that the conditioned medium of M-CSF-differentiated non-polarized macrophages (induced by macrophage CSF) suppressed TGF-β-induced differentiation, reduced the expression of myofibroblast markers (α-smooth muscle actin and vimentin), and decreased the contractile activity of lung myofibroblasts, while the conditioned media of dexamethasone-polarized macrophages and GM-CSF-differentiated non-polarized macrophages (differentiation stimulus is granulocyte-macrophage CSF) produced no such effects. Thus, the obtained data indicate the antifibrogenic potential of non-polarized M-CSF-differentiated macrophages.

Keywords:  conditioned medium; differentiation; human macrophages; lung fibroblasts; polarization

DOI:  https://doi.org/10.1007/s10517-025-06353-7
Mol Immunol. 2025 Mar 25. pii: S0161-5890(25)00078-1. [Epub ahead of print]181 129-138

Darutoside promotes skin wound healing via regulating macrophage polarization.

Linpei Gao, Jing Su, Lijia Guo, Sheng Lin, Junji Xu, Yi Liu.

  Wound healing is a complex and dynamic process of tissue formation, while polarization of macrophages plays an important role during this process. Darutoside is one of the major components of the ethanol extract from Siegesbeckia, which has the effects of anti-inflammation, healing rheumatism and promoting joint health. To investigate whether darutoside could promote wound healing, we established full-thickness excisional cutaneous wound healing model in C57/BL6 mice and applied darutoside on the skin wounds. The results showed that darutoside can improve wound healing in mice. Mechanistically, we treated RAW264.7 and macrophages with darutoside in vitro, and found that darutoside inhibited the LPS-induced polarization and pro-inflammatory cytokines expression in macrophages by inhibiting NF-κB signaling pathway. For in vivo study, we also found that darutoside could promote the growth of epithelial cells in wound tissue and inhibit the expression of iNOS+ macrophages around wound tissue by IHC staining. In addition, we also found that darutoside could inhibit the expression of inflammatory factors in wound tissue by PCR. Our data revealed that darutoside could promote wound healing by regulating macrophage polarization via inhibition of NF-κB signaling pathway.

Keywords:  Darutoside; Macrophages; Wound healing

DOI:  https://doi.org/10.1016/j.molimm.2025.03.008
Front Immunol. 2025 ;16 1545339

Lipid metabolism in ferroptosis: mechanistic insights and therapeutic potential.

Daoyun Sun, Longfei Wang, Yufan Wu, Yi Yu, Yufeng Yao, Hongju Yang, Chunlin Hao.

  Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, plays a pivotal role in various physiological and pathological processes. In this review, we summarize the core mechanisms of ferroptosis, emphasizing its intricate connections to lipid metabolism, including fatty acid synthesis, phospholipid remodeling, and oxidation dynamics. We further highlight advancements in detection technologies, such as fluorescence imaging, lipidomics, and in vivo PET imaging, which have deepened our understanding of ferroptotic regulation. Additionally, we discuss the role of ferroptosis in human diseases, where it acts as a double-edged sword, contributing to cancer cell death while also driving ischemia-reperfusion injury and neurodegeneration. Finally, we explore therapeutic strategies aimed at either inducing or inhibiting ferroptosis, including iron chelation, antioxidant modulation, and lipid-targeted interventions. By integrating mechanistic insights, disease relevance, and therapeutic potential, this review provides a comprehensive perspective on ferroptosis as a crucial interface between lipid metabolism and oxidative stress.

Keywords:  antioxidant defense; ferroptosis; iron metabolism; lipid peroxidation; therapeutic targeting

DOI:  https://doi.org/10.3389/fimmu.2025.1545339
Cell Death Dis. 2025 Mar 22. 16(1): 198

LL37 complexed to double-stranded RNA induces RIG-I-like receptor signalling and Gasdermin E activation facilitating IL-36γ release from keratinocytes.

Jennifer Keller, Judit Danis, Isabella Krehl, Eleftheria Girousi, Takashi K Satoh, Barbara Meier-Schiesser, Lajos Kemény, Márta Széll, W Wei-Lynn Wong, Steve Pascolo, Lars E French, Thomas M Kündig, Mark Mellett.

The Interleukin-36 (IL-36) cytokine family have emerged as important players in mounting an inflammatory response at epithelial barriers and tailoring appropriate adaptive immune responses. As members of the Interleukin-1 superfamily, IL-36 cytokines lack a signal peptide for conventional secretion and require extracellular proteolysis to generate bioactive cytokines. Although the IL-36 family plays an important role in the pathogenesis of plaque and pustular psoriasis, little is known about the release mechanisms of these cytokines from keratinocytes and the physiological stimuli involved. Nucleic acid released from damaged or dying keratinocytes initiates early inflammatory signals that result in the breaking of tolerance associated with psoriasis pathogenesis onset. Cathelicidin peptide, LL37 binds to DNA or double-stranded RNA (dsRNA) and activates a type I Interferon responses in plasmacytoid dendritic cells and keratinocytes. Here, we demonstrate that LL37 binds to dsRNA and induces IL-36γ release from human primary keratinocytes. LL37/dsRNA complexes activate RIG-I-like Receptor signalling, resulting in Caspase-3 and Gasdermin E (GSDME) cleavage. Subsequent GSDME pore formation facilitates IL-36γ release. This response is magnified by priming with psoriasis-associated cytokines, IL-17A and IFNγ. IL-36γ release in this manner is largely independent of cell death in primary keratinocytes and lacked extracellular proteolysis of IL-36γ. Conversely, transfection of keratinocytes directly with dsRNA synthetic analogue, Poly(I:C) induces NLRP1 inflammasome activation, which facilitates IL-36γ expression and release in a GSDMD-dependent manner. Inflammasome-associated cell death also enables extracellular processing of IL-36γ by the release of keratinocyte-derived proteases. These data highlight the distinct responses triggered by dsRNA sensors in keratinocytes. Depending on the inflammatory context and magnitude of the exogenous threat, keratinocytes will release IL-36γ coupled with cell death and extracellular cleavage or release the inactive pro-form, which requires subsequent processing by neutrophil proteases to unleash full biological activity, as occurring in psoriatic skin. Cytoplasmic sensing of dsRNA in keratinocytes mediates IL-36γ release via caspase activity and GSDM pore formation Keratinocytes release IL-36γ upon stimulation with intracellular dsRNA alone or complexed to the psoriasis-associated cathelicidin anti-microbial peptide LL37. Left: Transfected dsRNA triggers NLRP1 inflammasome assembly and IL-1β release, which can enhance IL-36γ expression, resulting in IL-36γ release and extracellular cleavage by released proteases. Right: LL37/dsRNA complexes activate a MDA5-MAVS pathway facilitating the release of IL-36γ through Caspase-3 activation and GSDME pore formation.

DOI: https://doi.org/10.1038/s41419-025-07537-9
Biology (Basel). 2025 Mar 16. pii: 299. [Epub ahead of print]14(3):

Mutual Interactions Between Microbiota and the Human Immune System During the First 1000 Days of Life.

Muy Heang Tang, Ishbel Ligthart, Samuel Varga, Sarah Lebeer, Frans J van Overveld, Ger T Rijkers.

  The development of the human immune system starts during the fetal period in a largely, but probably not completely, sterile environment. During and after birth, the immune system is exposed to an increasingly complex microbiota. The first microbiota encountered during passage through the birth canal colonize the infant gut and induce the tolerance of the immune system. Transplacentally derived maternal IgG as well as IgA from breast milk protect the infant from infections during the first 100 days, during which the immune system further develops and immunological memory is formed. The Weaning and introduction of solid food expose the immune system to novel (food) antigens and allow for other microbiota to colonize. The cells and molecules involved in the mutual and intricate interactions between microbiota and the developing immune system are now beginning to be recognized. These include bacterial components such as polysaccharide A from Bacteroides fragilis, as well as bacterial metabolites such as the short-chain fatty acid butyrate, indole-3-aldehyde, and indole-3-propionic acid. All these, and probably more, bacterial metabolites have specific immunoregulatory functions which shape the development of the human immune system during the first 1000 days of life.

Keywords:  bacterial colonization; gut microbiota; mode of delivery; neonatal immune system; prenatal delivery; short-chain fatty acids (SCFAs)

DOI:  https://doi.org/10.3390/biology14030299
Nature. 2025 Mar 26.

New antibiotic that kills drug-resistant bacteria discovered in technician's garden.

Smriti Mallapaty.



Keywords:  Antibiotics; Medical research; Microbiology

DOI:  https://doi.org/10.1038/d41586-025-00945-z
Cell Death Discov. 2025 Mar 28. 11(1): 121

Proinflammatory cytokines sensitise mesenchymal stromal cells to apoptosis.

Natalie L Payne, Swee Heng Milon Pang, Andrew J Freeman, Dilara C Ozkocak, Justin W Limar, Georgia Wallis, Di Zheng, Senora Mendonca, Lorraine A O'Reilly, Daniel H D Gray, Ivan K H Poon, Tracy S P Heng.

Mesenchymal stromal cells (MSCs) exert broad therapeutic effects across a range of inflammatory diseases. Their mechanism of action has largely been attributed to paracrine signalling, orchestrated by an array of factors produced by MSCs that are collectively termed the "secretome". Strategies to enhance the release of these soluble factors by pre-exposure to inflammatory cytokines, a concept known as "licensing", is thought to provide a means of enhancing MSC efficacy. Yet, recent evidence shows that intravenously infused MSCs entrapped within the lungs undergo apoptosis, and their subsequent clearance by host phagocytes is essential for their therapeutic efficacy. We therefore sought to clarify the mechanisms governing regulated cell death in MSCs and how exposure to inflammatory cytokines impacts this process. Our results show that MSCs are relatively resistant to cell death induced via the extrinsic pathway of apoptosis, as well as stimuli that induce necroptosis, a form of regulated inflammatory cell death. Instead, efficient killing of MSCs required triggering of the mitochondrial pathway of apoptosis, via inhibition of the pro-survival proteins MCL-1 and BCL-XL. Apoptotic bodies were readily released by MSCs during cell disassembly, a process that was inhibited in vitro and in vivo when the apoptotic effectors BAK and BAX were genetically deleted. Licensing of MSCs by pre-exposure to the inflammatory cytokines TNF and IFN-γ increased the sensitivity of MSCs to intrinsic apoptosis in vitro and accelerated their in vivo clearance by host cells within the lungs after intravenous infusion. Taken together, our study demonstrates that inflammatory "licensing" of MSCs facilitates cell death by increasing their sensitivity to triggers of the intrinsic pathway of apoptosis and accelerating the kinetics of apoptotic cell disassembly.

DOI: https://doi.org/10.1038/s41420-025-02412-0
Nat Immunol. 2025 Mar 26.

ImmGenMaps, an open-source cartography of the immune system.

ImmGenMaps Group

DOI: https://doi.org/10.1038/s41590-025-02119-5
Pathogens. 2025 Feb 26. pii: 229. [Epub ahead of print]14(3):

For Better or Worse: Type I Interferon Responses in Bacterial Infection.

Aihong Xia, Xin Li, Changjing Zhao, Xiaojing Meng, Gulmela Kari, Yongjuan Wang.

  Type I interferons (IFNs) are pleiotropic cytokines, primarily comprising IFN-α and IFN-β, and their effect in host defense against viral infection has been extensively studied and well-established. However, in bacterial infection, the role of type I IFNs is more complex, exhibiting multifaceted effects that depend on several factors, such as the pathogen species, the specific cell populations, and the routes of infection. In this review, we summarize research progress on host type I interferon responses triggered by specific bacteria and their immune regulation function in order to better understand the role of type I IFNs in bacterial infection and provide insights for adjuvant therapies tailored to treat specific bacterial infections.

Keywords:  bacterial infection; immune regulation; type I interferons

DOI:  https://doi.org/10.3390/pathogens14030229
Curr Opin Microbiol. 2025 Mar 24. pii: S1369-5274(25)00021-9. [Epub ahead of print]85 102599

The role of microbial succinate in the pathophysiology of inflammatory bowel disease: mechanisms and therapeutic potential.

Sonia Fernández-Veledo, Carme Grau-Bové, Sara Notararigo, Isabel Huber-Ruano.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition linked to gut microbiota dysbiosis and altered production of bacterial metabolites, including succinate, which is also a key intermediate in human mitochondrial energy metabolism in human cells. Succinate levels in the gut are influenced by microbial community dynamics and cross-feeding interactions, highlighting its dual metabolic and ecological importance. Extracellular succinate acts as a key signaling metabolite linking microbial metabolism to host physiology, with transient rises supporting metabolic regulation but chronic elevations contributing to metabolic disorders and disease progression. Succinate signals through its cognate receptor SUCNR1, which mediates adaptive metabolic responses under normal conditions but drives inflammation and fibrosis when dysregulated. IBD patients display a dysbiotic gut microbiota characterized by an increased prevalence of succinate-producing bacteria, contributing to elevated succinate levels in the gut and circulation. This imbalance drives inflammation, worsens IBD severity, and contributes to complications like Clostridioides difficile infection and fibrosis. Emerging evidence highlights the potential of intestinal and systemic succinate levels as indicators of microbial dysbiosis, with a bidirectional relationship between microbial composition and succinate metabolism. Understanding the factors influencing succinate levels and their interaction with dysbiosis shows promise in the development of therapeutic strategies to restore microbial balance. Approaches such as dietary fiber enrichment, prebiotics, and probiotics to enhance succinate-consuming bacteria, combined with targeted modulation of succinate pathways (e.g. SDH inhibitors, SUCNR1 antagonists), hold promise for mitigating inflammation and improving gut health in IBD.

DOI: https://doi.org/10.1016/j.mib.2025.102599
Food Funct. 2025 Mar 28.

Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation.

Shiying Wu, Yuenuo Luo, Fangtong Wei, Yanan Li, Jiayi Fan, Yongqiang Chen, Wenjie Zhang, Xuelong Li, Yang Xu, Ziqi Chen, Chenlan Xia, Mingyang Hu, Ping Li, Qing Gu.

Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.

DOI: https://doi.org/10.1039/d4fo06308b
Aging Dis. 2025 Mar 27.

Lactylation: A Novel Epigenetic Regulator of Cellular Senescence.

Caiyu Sun, Jiaxuan Li, Lei Dong, Yakui Mou, Bei Zhang, Xicheng Song.

Cellular senescence is the basic unit of organismal aging, a complicated biological process involving several cell types and tissues. It is also an important mechanism by which the body responds to damage and potential carcinogenesis. However, excessive or abnormal cellular senescence can lead to tissue functional degradation and the occurrence of diseases. In recent years, the role of epigenetic modifications in cellular senescence has received extensive attention. Lactylation, a novel post-translational modification derived from lactate, has recently gained significant attention as a key factor in cellular metabolism and epigenetic regulation, gradually demonstrating its importance in the regulation of cellular senescence. This review emphasizes the bidirectional causal relationship between lactylation and cellular senescence, highlighting its potential as a therapeutic target for aging-related diseases.

DOI: https://doi.org/10.14336/AD.2025.0277
Life (Basel). 2025 Mar 15. pii: 469. [Epub ahead of print]15(3):

Interleukin 8 Molecular Interplay in Allergic Rhinitis and Chronic Rhinosinusitis with Nasal Polyps: A Scoping Review.

Romica Cergan, Ovidiu Berghi, Mihai Dumitru, Daniela Vrinceanu, Felicia Manole, Gabriela Cornelia Musat, Alina Lavinia Antoaneta Oancea, Crenguta Serboiu.

  The present scoping review underlines the molecular interplay between allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), and interleukin-8 (IL-8). A query of PubMed database resulted in the inclusion of 34 articles in the final analysis of this scoping review. IL-8 is one interconnecting immune mediator in the physiopathology of AR and CRS. An influx of cytokines, such as interleukin (IL)-4 and IL-13, occurs from mast cells, four to six hours after the initial response signifying the development of the late-phase response allowing the entrance of eosinophils, basophils, and T-lymphocytes at the level of nasal mucosa. Chronic rhinosinusitis (CRS) is a chronic inflammatory disease that occurs in the mucosa of the nasal cavity and sinuses with two external phenotypes, but with molecular mechanisms that overlap with allergic rhinitis. Interleukin 8 induces neutrophil chemokinetic movement providing a chemotactic or directional cue. Clinical and fundamental studies established an implication of IL-8 in the disease mechanism of allergic rhinitis and CRSwNP. Moreover, there is still missing a randomized, large-cohort study with three patients groups (normal control, AR, CRSwNP) that analyzes the impact of IL-8 simultaneously. Future possible developments could focus on IL-8 as possible target for biologic treatments.

Keywords:  allergic rhinitis; interleukin; sinusitis

DOI:  https://doi.org/10.3390/life15030469
Metabolites. 2025 Mar 01. pii: 162. [Epub ahead of print]15(3):

Toll-like Receptor Activation Remodels the Polyamine and Tryptophan Metabolism in Porcine Macrophages.

Meimei Zhang, Lingfei Du, Yinhao Shen, Peng Bin.

  Background: The early nutritional metabolism of piglets is intimately associated with the regulation of immune function, and amino acids play a crucial role in modulating the fate and function of porcine immune cells, especially macrophages. However, the metabolic changes upon macrophage activation remain elusive. Methods: We established an in vitro activation model of porcine macrophages and investigated alterations in metabolites involved in polyamine and tryptophan metabolism upon activation by various toll-like receptor (TLR) activators. Results: TLR activation inhibits the production of spermine and alters the kynurenine pathway of the tryptophan metabolism toward the kynurenic acid biosynthesis. Specifically, TLR9 activation redirects the metabolic pathway of tryptophan toward kynurenic acid synthesis, which subsequently inhibits melatonin production via the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)/cAMP-responsive element-binding protein (CREB) signaling pathways. Conclusions: TLR activation reprograms the polyamine and tryptophan metabolism in porcine macrophages. Knowledge of the metabolic alterations in polyamine and tryptophan upon TLR activation in macrophages offers valuable insights and potential strategies for nutritional intervention to enhance piglet immunity.

Keywords:  Macrophage; TLRs; polyamine; tryptophan

DOI:  https://doi.org/10.3390/metabo15030162
Microb Pathog. 2025 Mar 21. pii: S0882-4010(25)00224-4. [Epub ahead of print]203 107499

Caspase-1 is critical for mice in the defense against Streptococcus equi subsp. zooepidemicus infection by promoting macrophage phagocytosis.

Shun Li, Yunfei Huang, Qinqin Sun, Yajuan Li, Honglin Xie, Qiang Fu.

  Streptococcus equi subsp. zooepidemicus (SEZ) is an important pathogen which is responsible for a wide range of diseases in various species. Macrophages are professional phagocytes that can engulf microorganisms and trigger responses leading to microbial death. Caspase-1 is considered as a proinflammatory factor that mediates antibacterial response to protect hosts from bacteria. Here, we revealed a novel role of Caspase-1 in mice against SEZ. Through both in vitro and in vivo infection assays, we demonstrated that the maturation and secretion of the cytokine IL-1β are critically dependent on Caspase-1 activation. The Caspase-1 deficient mice displayed attenuation of bactericidal activity against SEZ, mainly by decreasing the accumulation of macrophage. In addition to the recruitment of macrophages, deficiency of Caspase-1 also impaired the phagocytosis of SEZ by macrophages. Our study demonstrated that Caspase-1 is critical for mice to defense against SEZ depending on the recruitment and phagocytosis of macrophage.

Keywords:  Caspase-1; Macrophage; Phagocytosis; Recruitment; Streptococcus equi subsp. zooepidemicus

DOI:  https://doi.org/10.1016/j.micpath.2025.107499
Food Funct. 2025 Mar 27.

Bifidobacterium breve HH079 alleviates early-life antibiotic-exposed colon dysbiosis in mice by restoring the gut microbiota and gut barrier function.

Zhipeng Gu, Zerong Lu, Jian-Yong Wu, Zhuqing Xie, Ruibiao Hu, Qiang Huang, Feitong Liu, Bin Zhang.

Antibiotic exposure in early life disrupts gut microbiota development in infants, which could result in intestinal dysfunction. This study mimicked early-life antibiotic exposure in mice by administering antibiotic water to lactating dams, and investigated the effects of a new strain of Bifidobacterium breve HH079 (B. breve HH079) on intestinal dysbiosis associated with early-life antibiotic exposure in pups. The results showed that B. breve HH079 treatment inhibited the proliferation of Pseudomonas and Morganella after antibiotic exposure, but promoted the abundance of Bifidobacterium and Bacteroides and acetate production. Concomitantly, the B. breve HH079 administration resulted in decreased M1 gene (Cd86) and protein (TNF-α, IL-1β, LBP and iNOS) expression and increased M2 macrophage marker (Cd206, IL-10 and Arg1) expression in the colonic macrophages of antibiotic-exposed pups, probably by inhibiting the TLR4/NF-κB pathway. Moreover, there was increased intestinal epithelial tight junction protein (Cldn1 and Ocln) expression and the transcription of marker gene (Lyz2, Igha and Reg3β) normalization involved in innate immunity. The results suggested that the new B. breve HH079 strain could alleviate early-life antibiotic-induced colon dysbiosis by regulating the gut microbiota and promoting acetate production and the subsequent M2 macrophage polarization to recover gut health.

DOI: https://doi.org/10.1039/d5fo00535c
Viruses. 2025 Feb 28. pii: 349. [Epub ahead of print]17(3):

Recent Advances in Nose and Lung Organoid Models for Respiratory Viral Research.

Lennart Svensson, Johan Nordgren, Åke Lundkvist, Marie Hagbom.

  Studies on human respiratory viral infections and pathogenesis have historically been conducted using immortalized cells and animal models. However, these models are limited in their ability to recapitulate the complex structure of the human airway or the full spectrum of disease symptoms observed in humans. Recently, nose and lung organoids have revolutionized culture complexity in infection biology and have demonstrated potential for research on respiratory virus infections in humans. In this opinion, we review how advances in human nose and lung organoid models, which are able to express all cell types of the respiratory epithelia, i.e., Club, basal, goblet, and ciliated cells, have provided novel insight into the pathogenesis, age-dependent susceptibility, viral attenuation signature, and immune mechanisms of respiratory viruses such as SARS-CoV-2, respiratory syncytial virus, and influenza virus. The models have also demonstrated potential for studying hitherto uncultivable human viruses and to be useful for studies of zoonotic risk.

Keywords:  human; lung; nasal; organoids; respiratory virus; stem cells

DOI:  https://doi.org/10.3390/v17030349
Biochem Pharmacol. 2025 Mar 22. pii: S0006-2952(25)00154-6. [Epub ahead of print]236 116892

Activated Notch1 promotes macrophage polarization and exacerbates sepsis-induced acute lung injury via β-catenin/NF-κB signaling.

Zhi Liu, Yuxi Lei, Jing Zuo, Ruiyu Zhang, Hui Du, Huizhi Hu, Junwen Zheng, Pu Yang, Dongchi Zhao.

  Sepsis-induced acute lung injury (ALI) is a critical condition characterized by excessive inflammation, with macrophage polarization playing a pivotal role in its pathogenesis. In this study, we constructed myeloid-specific Notch1 knockout mice, overexpressed the Notch intracellular domain (NICD), and inhibited β-catenin using XAV939 to investigate the impact and mechanisms of Notch1 regulation in macrophage polarization and inflammatory responses in cecal ligation and puncture (CLP)-induced septic mice. The results demonstrated that Notch1 knockout significantly reduced M1 macrophage polarization, alleviated systemic inflammation, mitigated lung injury, and improved survival in septic mice. In sepsis, Notch1 enhances β-catenin expression, which synergizes with the NF-κB pathway to promote M1 polarization and pro-inflammatory cytokine production. Specifically, NICD interacts with β-catenin in macrophages, amplifying NF-κB activation and its nuclear translocation. These results demonstrate that the Notch1 signaling pathway plays a pivotal role in regulating macrophage phenotypic switching, highlighting its potential as a therapeutic target for attenuating sepsis-associated ALI through immune homeostasis restoration.

Keywords:  Acute lung injury; Macrophage polarization; Notch1; Sepsis; β-catenin

DOI:  https://doi.org/10.1016/j.bcp.2025.116892
Curr Pharm Des. 2025 Mar 13.

Advanced Membrane Simulations in Probiotics and Gut Microbiome Interaction Research: The Current Trends and Insights.

Yashika Gupta, Bhavya Sharma, Chakresh Kumar Jain.

  The gut microbiome, a complex and diverse microbial ecosystem, plays a pivotal role in maintaining host health by regulating physiological balance and preventing disease. Probiotics, live beneficial microorganisms, have shown potential in modulating the gut microbiota through mechanisms such as competitive exclusion of pathogens, enhancement of mucosal immunity, and regulation of microbial metabolism. Recent advancements in membrane simulations offer a novel approach to studying these interactions at the molecular level. By employing molecular dynamics (MD) and coarse-grained models, these simulations provide insights into the structural and functional dynamics of bacterial membranes and their interactions with probiotics. This approach enables a deeper understanding of key processes, such as microbial metabolite transport, membrane permeability, and host response modulation, which are critical for maintaining gut homeostasis. Additionally, membrane simulations facilitate the exploration of microbial communication pathways, enhancing our knowledge of the molecular mechanisms underlying the beneficial effects of probiotics. As computational tools evolve, integrating membrane simulations with experimental approaches can accelerate the discovery of targeted probiotic therapies aimed at restoring microbial balance and optimizing gut health. This review underscores the significance of membrane simulations in advancing gut microbiome research, suggesting that future studies should focus on refining these computational models to bridge the gap between theoretical predictions and clinical applications. Through a synergistic approach, researchers can enhance the therapeutic potential of probiotics, leading to improved strategies for managing gut-related disorders with insightful knowledge of their interactions.

Keywords:  Gut microbiome; computational biology; gut health; host-microbe interactions; immune modulation.; membrane simulations; microbial interactions; microbial metabolite transport; molecular dynamics; probiotics

DOI:  https://doi.org/10.2174/0113816128357214250221053909
Microorganisms. 2025 Feb 28. pii: 547. [Epub ahead of print]13(3):

Refining Unfavorable Vaginal Microbial Community in Infertile Women Subjected to Precision Probiotic Intervention: An Exploratory Single-Arm, Prospective, Open-Label, Interventional Study.

Giovanna Cocomazzi, Viviana Contu, Silvia De Stefani, Lino Del Pup, Matteo Buccheri, Monica Antinori, Lodovico Parmegiani, Daniele De Ruvo, Francesco Marino, Edy Virgili, Christine Allen, Simone Palini, Walter Ciampaglia, Matteo Cerboneschi, Domenico Baldini, Giorgio Maria Baldini, Valerio Pazienza.

   BACKGROUND AND AIMS: Vaginal microbiomes have been classified into five different general categories, termed Community State Type (CSTs), with CST-III and CST-IV often associated with vaginal dysbiosis which makes women more prone to recurrent infections and assisted reproductive technology (ART) failure. Since a healthy microbiome is one of the key steps for successful reproduction, we investigated the impact of modulating the vaginal microbiota through the oral administration of probiotic formula consisting of a consortium of vaginal-specific lactobacilli and prebiotics (Personal Flora 2®).
METHODS: We recruited 32 women who had previous failed IVF cycles and were scheduled to undergo ART. We examined the composition of the vaginal microbiota before and after oral probiotic supplementation using 16S ribosomal RNA (rRNA) sequencing technology.
RESULTS: Our data show a noticeable modulation of the vaginal microbiome upon probiotic supplementation. In particular, precision probiotic intervention lowers the species diversity, favoring the dominance of Lactobacillus (p = 0.015) and Bifidobacterium (p = 0.000) whilst decreasing the percentage of Atopobium (p = 0.003), Gardnerella (p = 0.022), and Prevotella (p = 0.000).
CONCLUSIONS: Although CST-III and CST-IV are generally considered detrimental, gynecologists should not refrain from performing IVF in these women if they have been previously subjected to a consortium of precision probiotics treatments, as the administration of specific probiotics reduces the presence of pathogenic bacteria promoting the increase in lactobacilli associated with a healthy vaginal ecosystem, which could impact pregnancy success.

Keywords:  infertility; probiotics; vaginal microbiome

DOI:  https://doi.org/10.3390/microorganisms13030547
Future Microbiol. 2025 Mar 28. 1-10

Functional efficacy of Enterococcus faecium HN4 and Lactobacillus delbrueckii HN5 strains isolated from human milk.

Harsha Nirvan, Garima Deswal, Manjit K Selwal, Krishan Kumar Selwal.

   AIMS: The microbiota of human milk is described at length; however, variation in different bacterial genera in milk has been reported. Here, breast milk samples from Indian mothers were used to target bacterial species from the pool of microbial communities in human milk with probiotic potential.
MATERIALS AND METHODS: A culture-dependent technique was used to isolate bacterial cultures, and their physiological and functional properties were appraised.
RESULTS: Two bacterial cultures, E. faecium HN4 and L delbrueckii HN5, were identified as showing considerable tolerance to acid and bile conditions with 73.0-87.0% survival. The cultures showed other in vitro beneficial properties.
CONCLUSION: The study highlights the presence of potential probiotics in human milk that could be investigated for further use.

Keywords:  Human milk; Probiotic; antibiotic susceptibility; antimicrobial activity; antioxidant potential

DOI:  https://doi.org/10.1080/17460913.2025.2484924
Nat Rev Microbiol. 2025 Mar 21.

Human microbiome acquisition and transmission.

Vitor Heidrich, Mireia Valles-Colomer, Nicola Segata.

As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.

DOI: https://doi.org/10.1038/s41579-025-01166-x
Pathogens. 2025 Mar 04. pii: 251. [Epub ahead of print]14(3):

Nutritional Stress Leads to Persistence and Persister-like Growth in Staphylococcus aureus.

Katie R Risoen, Claire A Shaw, Bart C Weimer.

  Staphylococcus aureus is a versatile zoonotic pathogen capable of causing a wide range of infections. Due to the organism's ability to persist, recalcitrant and recurring infections are a major concern for public and animal health. This study investigated the establishment of persistence using two S. aureus strains-ATCC 29740, a bovine mastitis isolate, and USA300, a human clinical isolate-under substrate depletion. This nutritional stress established a persistence phenotype where the strains remained persistent for >120 days at notable concentrations [>2 log10 CFU/mL] and developed persister-like growth, including small colony variant formations. With RT-qPCR, we found the cell density was higher than represented by the plate count while the intracellular ATP remained constant during the persistence phase. These findings indicate that S. aureus has complex survival strategies to support its persistent state, providing a host-specific perspective when addressing recurrent infections in human and animal infectious diseases.

Keywords:  MRSA; bovine mastitis; non-culturable; nutritional stress; persistence; persisters; small colony variants

DOI:  https://doi.org/10.3390/pathogens14030251
Expert Opin Biol Ther. 2025 Mar 28. 1-14

Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.

Samantha Flores-Treviño, Paola Bocanegra-Ibarias, Daniel Salas-Treviño, María Teresa Ramírez-Elizondo, Eduardo Pérez-Alba, Adrián Camacho-Ortiz.

   INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.
AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.
EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.

Keywords:  Dysbiosis; fecal microbiota transplantation; live biotherapeutic products; synthetic bacterial consortium; vaginal microbiota transplantation

DOI:  https://doi.org/10.1080/14712598.2025.2484303
Hum Mol Genet. 2025 Mar 26. pii: ddae177. [Epub ahead of print]

Dual faces of itaconate and its derivatives: exploring diverse biological functions in immunity and infectious diseases.

Cecilie Poulsen, Dominic G Roy, David Olagnier.

  The intersection of immunology and infectious diseases has been revolutionized by the emergence of immunometabolism, highlighting the critical role of metabolic processes in regulating immune responses. In recent years, itaconate alongside its derivatives dimethyl-itaconate (DMI) and 4-octyl-itaconate (4-OI), have received attention for their potent immunomodulatory and antimicrobial properties. This review examines the unique roles of itaconate and its derivatives in modulating immune functions and their implications in infectious diseases. We also explore their structural and functional discrepancies. Notably, while itaconate generally exhibits anti-inflammatory and antimicrobial effects, its derivatives may operate through distinct mechanisms, often exhibiting enhanced electrophilic properties. This review of recent research underscores the potential of itaconate and its derivatives as therapeutic agents, paving the way for future clinical applications in managing inflammation and infectious diseases.

Keywords:  antimicrobial activity; immunometabolism; inflammation; itaconate; itaconate derivatives

DOI:  https://doi.org/10.1093/hmg/ddae177
Trends Cell Biol. 2025 Mar 21. pii: S0962-8924(25)00061-3. [Epub ahead of print]

Versatility of gasdermin D beyond pyroptosis.

Tianming Zhao, Zhexu Chi, Di Wang.

  Gasdermin D (GSDMD) has garnered significant attention primarily for the pore-forming role of its p30 N-terminal fragment (NT-p30) generated during pyroptosis, a proinflammatory form of cell death. However, emerging evidence suggests that the formation of GSDMD-NT pores is reversible, and the activation of GSDMD does not necessarily lead to pyroptosis. Instead, this process may take part either in other forms of cell death, or in various state changes of living cells, including (i) inflammation regulation, (ii) endolysosomal pathway rewiring, (iii) granule exocytosis, (iv) type II immunity, (v) food tolerance maintenance, and (vi) temporary permeability alteration. This review explores the latest insights into the involvement of GSDMD in cell death and homeostasis maintenance, aiming to underscore the pleiotropic nature of GSDMD.

Keywords:  cell death; gasdermin D; homeostasis; pyroptosis

DOI:  https://doi.org/10.1016/j.tcb.2025.02.011