Lactiplantibacillus plantarum FRT4 protects against fatty liver hemorrhage syndrome: regulating gut microbiota and FoxO/TLR-4/NF-κB signaling pathway in laying hensLi, Meng, Liu
et alMicrobiome (2025) 13 (1), 88
Abstract: Fatty liver hemorrhage syndrome (FLHS) has become one of the major factors leading to the death of laying hen in caged egg production. FLHS is commonly associated with lipid peroxidation, hepatocyte injury, decreased antioxidant capacity, and inflammation. However, there are limited evidences regarding the preventive effect of Lactiplantibacillus plantarum on FLHS in laying hens and its mechanisms. Our previous results showed that Lp. plantarum FRT4 alleviated FLHS by regulating lipid metabolism, but did not focus on its antioxidant and anti-inflammatory functions and mechanisms. Therefore, this study aimed to investigate the preventive mechanisms of Lp. plantarum FRT4 in alleviating FLHS, with a focus on its role in antioxidant activity and inflammation regulation.Supplementation with Lp. plantarum FRT4 enhanced the levels of T-AOC, T-SOD, and GSH-Px, while reducing the levels of TNF-α, IL-1β, IL-8, and NLRP3 in the liver and ovary of laying hens. Additionally, Lp. plantarum FRT4 upregulated the mRNA expressions of SOD1, SOD2, CAT, and GPX1, downregulated the mRNA expressions of pro-inflammatory factors IL-1β, IL-6, and NLRP3, and upregulated the mRNA expressions of anti-inflammatory factors IL-4 and IL-10. Lp. plantarum FRT4 improved the structure and metabolic functions of gut microbiota, and regulated the relative abundances of dominant phyla (Bacteroidetes, Firmicute, and Proteobacteria) and genera (Prevotella and Alistipes). Additionally, it influenced key KEGG pathways, including tryptophan metabolism, amino sugar and nucleotide sugar metabolism, insulin signaling pathway, FoxO signaling pathway. Spearman analysis revealed that the abundance of microbiota at different taxonomic levels was closely related to antioxidant enzymes and inflammatory factors. Furthermore, Lp. plantarum FRT4 modulated the mRNA expressions of related factors in the FoxO/TLR-4/NF-κB signaling pathway by regulating gut microbiota. Moreover, the levels of E2, FSH, and VTG were significantly increased in the ovary after Lp. plantarum FRT4 intervention.Lp. plantarum FRT4 effectively ameliorates FLHS in laying hens. This efficacy is attributed to its antioxidant and anti-inflammatory properties, which are mediated by modulating the structure and function of gut microbiota, and further intervening in the FoxO/TLR-4/NF-κB signaling pathway. These actions enhance hepatic and ovarian function and increase estrogen levels. Video Abstract.© 2025. The Author(s).
Effects of Chinese herbal formula (including Houttuyniae Herba, Pulsatilliae Radix, Scutellariae Radix) supplementation in drinking water on growth performance, intestinal barrier function, and cecum microbiome composition of broilers under necrotic enteritis challengeDu, Ai, Miao
et alRes Vet Sci (2025) 189, 105631
Abstract: We evaluated the antimicrobial activity of a Chinese herbal formula (CHF) (comprising Houttuyniae Herba, Artemisia Annua L., Pulsatilliae Radix, Radix Sanguisorbae, Aucklandiae Radix, Scutellariae Radix, Anemarrhenae Rhizoma, Semen Pharbitidis, and Radix Rhei Et Rhizome) and its protective effects against necrotic enteritis (NE) in broiler chickens. The in vitro results demonstrated significant antibacterial activity against Clostridium perfringens, as well as a positive effect of CHF on cell viability when exposed to this bacterium. In the in vivo experiments, 360 ten-day-old broilers were randomly assigned to six groups: control, NE, NE + lincomycin, NE + 2.5 g/L CHF, NE + 5 g/L CHF, and NE + 10 g/L CHF. The CHF-supplemented drinking water significantly improved the growth performance of the NE-challenged broilers. CHF supplementation improved intestinal barrier function and integrity in NE-challenged broilers by enhancing jejunal morphology, increasing the mRNA levels of tight junction proteins (zonula occludens-1 and occludin) and reducing intestinal permeability (serum D- lactic acid levels and diamine oxidase activity). Supplementation with the CHF also reduced systemic and jejunum pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, TNF-α, IFN-γ) and increased anti-inflammatory factors (IL-4 and IL-10) in NE-challenged broilers by inhibiting the nuclear factor kappa B and signal transducers and activators of transcription signaling pathways. Cecal microbiota analysis revealed that supplementation with the CHF increased the abundance of beneficial bacteria (Faecalibacterium, Bacteroides, and Butyricimonas) in NE-challenged broilers. In conclusion, drinking water supplemented with the CHF enhanced growth performance, improved intestinal barrier function, and reduced systemic inflammatory responses in C. perfringens-challenged broilers. The recommended optimal dose of the CHF in drinking water is 5 g/L.Copyright © 2025 Elsevier Ltd. All rights reserved.
No Distinct Cytokine, Chemokine, and Growth Factor Blood Profile Associated With Monkeypox Virus Clade IIb Infected PatientsBangwen, Berens-Riha, de Vrij
et alJ Med Virol (2025) 97 (4), e70320
Abstract: Previous studies indicated Clade I monkeypox virus infection to be associated with marked elevation of proinflammatory cytokines. This remains unexplored for Clade II-associated disease, which has different clinical manifestations and prognosis. We used a 65-plex cytokine, chemokine, and growth factor (CCG) panel to analyze serum samples of 100 male acute Clade IIb mpox patients and 26 healthy controls in Belgium. Cluster analyses revealed no strong or distinct CCG profiles distinguishing mpox patients from controls but suggested trends in certain cytokine modulation. Individual CCG analyses found elevated levels of cytokines (MIF, CD30, IL2R, IL18, APRIL, and TNFRII), chemokines (CCL4, CCL8, CCL22, CCL24, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13), and growth factors (HGF and VEGFA) in patients, while CCL11 and CXCL5 were significantly suppressed. We detected no differences in key proinflammatory cytokines, IL-1α, IL-1β, IL-6, IL-8 or anti-inflammatory cytokines, IL-4, IL-10, IL-13. In patients living with HIV, comparison with pre-outbreak samples showed an increase in CXCL13 and a decrease in CXCL5, CCL2, CCL24, HGF, SCF, and TWEAK. The absence of discriminatory CCG profiles in Clade IIb mpox patients compared to healthy controls suggests there may be limited clinical applications of those markers.© 2025 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.
Crosstalk between metabolism and epigenetics during macrophage polarizationZhang, Jagannath
Epigenetics Chromatin (2025) 18 (1), 16
Abstract: Macrophage polarization is a dynamic process driven by a complex interplay of cytokine signaling, metabolism, and epigenetic modifications mediated by pathogens. Upon encountering specific environmental cues, monocytes differentiate into macrophages, adopting either a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype, depending on the cytokines present. M1 macrophages are induced by interferon-gamma (IFN-γ) and are characterized by their reliance on glycolysis and their role in host defense. In contrast, M2 macrophages, stimulated by interleukin-4 (IL-4) and interleukin-13 (IL-13), favor oxidative phosphorylation and participate in tissue repair and anti-inflammatory responses. Metabolism is tightly linked to epigenetic regulation, because key metabolic intermediates such as acetyl-coenzyme A (CoA), α-ketoglutarate (α-KG), S-adenosylmethionine (SAM), and nicotinamide adenine dinucleotide (NAD+) serve as cofactors for chromatin-modifying enzymes, which in turn, directly influences histone acetylation, methylation, RNA/DNA methylation, and protein arginine methylation. These epigenetic modifications control gene expression by regulating chromatin accessibility, thereby modulating macrophage function and polarization. Histone acetylation generally promotes a more open chromatin structure conducive to gene activation, while histone methylation can either activate or repress gene expression depending on the specific residue and its methylation state. Crosstalk between histone modifications, such as acetylation and methylation, further fine-tunes macrophage phenotypes by regulating transcriptional networks in response to metabolic cues. While arginine methylation primarily functions in epigenetics by regulating gene expression through protein modifications, the degradation of methylated proteins releases arginine derivatives like asymmetric dimethylarginine (ADMA), which contribute directly to arginine metabolism-a key factor in macrophage polarization. This review explores the intricate relationships between metabolism and epigenetic regulation during macrophage polarization. A better understanding of this crosstalk will likely generate novel therapeutic insights for manipulating macrophage phenotypes during infections like tuberculosis and inflammatory diseases such as diabetes.© 2025. The Author(s).
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