Search Results (1,408)

This study investigated the protective effects of DBD against Staphylococcus aureus (S. aureus)-induced mastitis in mice and explored whether these effects were associated with gut microbiota alterations, blood–milk barrier integrity, and inflammatory signaling. A lactating mouse model of mastitis was established, and the effects of DBD were evaluated using HPLC, histopathological analysis, ELISA, qRT-PCR, Western blotting, immunofluorescence, and 16S rRNA sequencing. The results showed that DBD significantly reduced bacterial loads in mammary tissues, decreased the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and alleviated inflammatory cell infiltration and tissue damage. Moreover, DBD upregulated the expression of tight junction proteins and improved the integrity of the blood–milk barrier. DBD treatment was also associated with alterations in gut microbiota composition, as reflected by changes in the relative abundance of several bacterial taxa. In addition, DBD inhibited the activation of the NF-κB/NLRP3 and MAPK inflammatory signaling pathways. Collectively, these findings indicate that DBD alleviates S. aureus-induced mastitis accompanied by alterations in gut microbiota composition, suppressing inflammatory responses, and repairing the blood–milk barrier, suggesting its potential as a therapeutic agent for mastitis. Full article

Mastitis remains the most economically damaging disease of dairy production, and recent molecular work has converged on the NLRP3 inflammasome as a key integrative node of its pathogenesis. This narrative review integrates evidence published largely between 2015 and 2026 to show how diverse triggers—Staphylococcus aureus and Escherichia coli, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), non-esterified fatty acids (NEFA), heat stress, environmental xenobiotics including nanoplastics, and microbiota-derived signals—may funnel into a common NLRP3–ASC–caspase-1–GSDMD axis that drives pyroptosis, blood–milk barrier disruption, and clinical disease. The review examines the potential obligatory role of reactive oxygen species (ROS), mitochondrial dysfunction, and selenoprotein-mediated redox control in licensing inflammasome assembly. It further evaluates the emerging gut–mammary and rumen–mammary axes that operate upstream of local epithelial activation. We survey a structurally diverse therapeutic landscape encompassing dietary selenium, probiotics, microbial metabolites, plant-derived nanovesicles, polyphenols, ginsenosides, and small-molecule NLRP3 antagonists, identifying recurring mechanistic motifs that suggest combinatorial regimens may yield additive benefit. Importantly, much of the evidence derives from in vitro and murine models, and we highlight the translational gaps that must be bridged before clinical application in dairy cattle. Finally, we map outstanding research gaps and propose priorities for translational work aimed at sustainable, antibiotic-sparing management of bovine mastitis. Full article

Background/Objectives: Acute lung injury (ALI) currently lacks safe and effective therapeutic strategies with low toxicity. Lonicerae japonicae flos, a traditional herb and functional food, contains polyphenols as its principal active components. This study investigated whether Lonicerae japonicae flos polyphenols (LJP) could exert protective effects against lipopolysaccharide (LPS)-induced ALI in mice. Methods: Eighty-four male C57BL/6J mice were randomly divided into seven groups and treated daily for 7 days with LJP (200, 100, or 50 mg/kg), liproxstatin-1 (10 mg/kg), dexamethasone (5 mg/kg), or saline (control and model groups). Subsequently, another thirty-six mice were used for the fecal microbiota transplantation (FMT) experiment. All groups except the control group received intratracheal instillation of LPS (5 mg/kg) to induce ALI. Results: LJP treatment significantly ameliorated lung histopathological damage and gut microbiota dysbiosis. Lung proteomics analysis revealed the enrichment of the NF-κB and ferroptosis pathways. Mechanistically, LJP downregulated pro-inflammatory factors (IL-6, TNF-α, and IL-1β) by suppressing activation of the TLR4/MyD88/NF-κB pathway. Meanwhile, LJP upregulated SOD and GSH levels, thereby suppressing the accumulation of ROS, GSSG, Fe²⁺, and MDA, which were closely related to the activation of the Nrf2/HO-1 and Sirt3/Nrf2/GPX4 pathways. Furthermore, LJP modulated the gut microbiota and promoted short-chain fatty acid (SCFA) production by elevating the relative abundance of Akkermansia muciniphila and Faecalibaculum. Intriguingly, FMT results confirmed that the LJP-derived gut microbiota markedly alleviated lung tissue injury and intestinal barrier damage in ALI mice. Conclusions: This study demonstrated that LJP could reshape the gut microbiota to enhance the production of SCFAs and inhibit inflammation-related ferroptosis in ALI mice. Full article

Aquatic organisms are exposed to multiple stressors, including microplastic pollution and rising temperatures. Bioplastics like Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are considered sustainable alternatives to conventional plastics, although their biological effects remain poorly understood. This study evaluated the effects of PHBV microplastics on Artemia franciscana under different temperature and exposure conditions. Organisms were exposed to 25 and 100 mg·L⁻¹ PHBV for 7, 14, and 21 days at 25 °C and for 14 days at 29 °C. Growth, development, antioxidant enzyme (CAT, GST) and esterase activities (ChE, CbE), lipid peroxidation (LPO), gut histology, fatty acid profiles and polymer particle length distributions were assessed. Growth and development increased with PHBV concentration, exposure time, and temperature. Enzymatic activities and LPO were significantly affected by these factors, although no evidence of oxidative damage was detected. Marked gut lesions were observed at 100 mg·L⁻¹ PHBV at 29 °C after 14 days. Fatty acid profiles were mainly influenced by time and temperature, while high PHBV levels were associated with additional, more subtle changes in long-chain polyunsaturated fatty acids. PHBV particle length distributions also varied depending on exposure conditions. These findings suggest that PHBV induces physiological responses distinct from those typically reported for conventional microplastics and highlight the importance of considering multiple stressors in ecotoxicological studies. Full article

Cytolysin-positive Enterococcus faecalis is a key pathogen in severe alcoholic hepatitis, yet the mechanisms through which it worsens disease and possible therapeutic strategies remain poorly understood. This study aimed to clarify the pathogenic effects of E. faecalis in acute alcohol-associated liver disease (ALD) and to assess the protective potential of Akkermansia muciniphila (Akk11) against this pathogen. Using a mouse model of acute ethanol gavage, animals received E. faecalis and/or Akk11 under prophylactic or therapeutic regimens. Assessments included liver injury markers, histopathology, lipid profiles, inflammatory cytokines, gut barrier integrity, and gut microbiota composition. E. faecalis exacerbated ethanol-induced hepatic steatosis and injury, showing a paradoxical effect: it increased histological damage while lowering circulating LPS and transaminases. This was linked to upregulated hepatic autophagy (increased Atg7) and reduced cholesterol, yet it promoted neutral lipid accumulation. Importantly, E. faecalis aggravated gut dysbiosis by markedly enriching the pro-inflammatory pathobiont Helicobacter typhlonius and impairing colonic barrier function. Intervention with Akk11 alleviated liver injury, reduced lipid accumulation and oxidative stress, and restored cytokine balance. Akk11 also strengthened gut barrier integrity, lowered serum endotoxin, and beneficially reshaped the microbiota. Prophylactic administration was particularly effective, normalizing the Firmicutes/Bacteroidota ratio, suppressing H. typhlonius, and enriching beneficial Bacteroides sartorii. This study confirms the pathogenic role of E. faecalis in acute ALD and establishes A. muciniphila (Akk11) as a promising microbiota-targeted therapy, which protects against liver injury by reinforcing the gut barrier, selectively modulating microbiota, and reducing inflammation, with prophylactic administration showing superior efficacy. Full article

Benzovindiflupyr (BZF) is a newly developed succinate dehydrogenase inhibitor (SDHI) fungicide that is widely used in crop protection, but its potential effects on non-target aquatic organisms remain a concern. In this study, we exposed adult zebrafish (Danio rerio) to 5.0 and 50 μg/L BZF for 28 days. We investigated its impact on the gut–liver axis using a combination of microbiome, biochemical, histological, and metabolomic analyses. BZF exposure damaged intestinal structure, downregulated barrier-related genes, and altered the composition of the gut microbiota. At the same time, serum lipopolysaccharide (LPS) levels increased, which indicates impaired intestinal barrier integrity and microbial dysbiosis. In the liver, BZF caused histopathological alterations, increased serum ALT, AST, and ALP activities, enhanced oxidative stress, and upregulated inflammation-related genes. Liver metabolomic profiling further showed marked disturbances in redox balance and metabolic homeostasis. Correlation analysis also revealed significant associations between altered microbial taxa and differential liver metabolites. Taken together, these results suggest that BZF exposure disrupted intestinal homeostasis and was associated with hepatic metabolic disturbance in zebrafish, potentially through gut–liver axis perturbation. This study expands current understanding of the toxic effects of SDHI fungicides and provides useful evidence for the ecological risk assessment of BZF in aquatic environments. Full article

Microplastics and nanoplastics (MNPLs) are increasingly recognized as dynamic vectors capable of transporting a wide range of environmental contaminants, as well as acting as physical particulates. Their small size, high surface reactivity and strong sorption capacity allow them to carry metals, pesticides, pharmaceuticals and endocrine-active compounds into biological systems. This narrative review examines how these particle-contaminant complexes influence oxidative stress, inflammatory signaling and endocrine function during early development. Relevant literature was identified through structured searches of PubMed, Scopus, Web of Science and Google Scholar, with a focus on the physicochemical properties of plastics, sorption mechanisms, gut barrier physiology and developmental toxicology. Early developmental stages are particularly sensitive, as immature mucus layers, permeable epithelial junctions and underdeveloped detoxification pathways facilitate the uptake and systemic distribution of MNPLs. Once internalized, these particles and their chemical cargo promote the generation of reactive oxygen species through redox-active contaminants, surface-catalysed reactions and mitochondrial dysfunction. The resulting oxidative imbalance activates stress-responsive pathways, including Nrf2–Keap1 signaling, and promotes lipid peroxidation, DNA damage and cellular dysfunction. MNPLs also stimulate inflammatory cascades by activating pattern-recognition receptors, altering cytokine profiles and disrupting epithelial homeostasis. These responses are intensified in the presence of sorbed pollutants, leading to sustained inflammatory states that can be particularly detrimental during organogenesis and immune maturation. Endocrine function is likewise affected, as MNPLs transport hormonally active chemicals and can interfere with hormone-responsive pathways through oxidative and inflammatory mechanisms. These interactions may disrupt thyroid signaling, metabolic regulation and the development of the reproductive axis, with potential long-term physiological consequences. Integrating evidence from polymer chemistry, contaminant behavior and developmental physiology, this review shows that MNPLs act as biologically active vectors that may increase oxidative, inflammatory and endocrine disturbances during early development. These findings highlight the importance of considering particle–contaminant interactions as a critical component of early-life risk assessment. Full article

Sepsis-associated encephalopathy (SAE) is a frequent neurological complication of sepsis, driven by six interconnected pathophysiological components: (1) systemic inflammation-triggered neuroinflammatory cascades, initiated by systemic recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and propagated by pro-inflammatory mediators; (2) central nervous system (CNS) immune cell-mediated neuroinflammation, wherein microglia, regulatory T cells, and neutrophils dynamically regulate inflammatory progression; (3) blood–brain barrier (BBB) disruption, progressing from functional disturbance to structural damage via tight junction degradation and immune infiltration; (4) multimodal programmed cell death, encompassing autophagy, apoptosis, pyroptosis, and ferroptosis driven by mitochondrial dysfunction; (5) neurotransmitter network imbalance, manifesting as cholinergic deficiency and glutamate excitotoxicity; and (6) gut–brain axis dysregulation, characterized by reduced microbiota-derived metabolites such as butyrate and indolepropionic acid. These components are organized along a core pathological axis comprising four sequential stages: neuroinflammatory storm (encompassing components 1 and 2) → BBB disruption and microcirculatory disturbances (component 3) → multimodal programmed cell death (component 4) → neurotransmitter imbalance (component 5), with the gut–brain axis (component 6) functioning as a bidirectional regulatory node that intersects and modulates all four stages. Mitochondrial dysfunction serves as the central converging node linking these pathological axes. Targeted interventions against neuroinflammation, immune cell modulation, BBB restoration, inhibition of aberrant cell death, neurotransmitter homeostasis, and gut microbiota remodeling hold therapeutic promise. Elucidating the crosstalk among these pathways will accelerate the clinical translation of precision therapies for SAE. Full article

Background: Natto, a well-known fermented soybean product beneficial for bone health, remains unclear in its mechanism. Methods: This study investigated its effect on secondary osteoporosis (OP) in mice. Results: Natto significantly inhibited weight loss, bone quality deterioration, and bone morphological damage, and regulated OPG/RANKL pathway protein expression (p < 0.05) in OP mice. Analysis of 16S rRNA revealed that natto increased gut microbiota α-diversity and the abundance of Sutterella, Roseburia, and Coprococcus, while reducing harmful bacteria such as Streptococcus, Shigella, and Helicobacter. These microbial changes positively correlated with body weight, bone size, and serum osteogenic metabolism in OP mice. Serum metabolomics showed differential metabolites of the natto group enriched in PPAR signaling and primary bile acid biosynthesis. Verification by mRNA and ELISA indicated that the upregulated liver and circulating PPARα by natto may regulate downstream bile acid pathways, linking gut microbiota to multi-organ metabolic functions. Conclusions: In summary, natto may act on gut microbiota to alleviate bone loss via the “gut microbiota–bile acid–OPG/RANKL” network, targeting multiple organs including gut, liver, and bone. This provides a theoretical basis for natto dietary intervention in osteoporosis prevention through the gut–bone axis. Full article

Microplastics are widespread environmental contaminants with adverse health impacts. The gastrointestinal tract represents a primary site for host–microplastic contact and interactions, but microplastic-driven perturbations of the gut microbiome and how they mediate toxicity to the gut and host’s health remain poorly elucidated. In this study, zebrafish (Danio rerio) were exposed to environmentally ubiquitous polyester microplastics and investigated for acute dysbiosis and host–microbiome molecular responses using an integrated histological and multi-omics approach. Gut transcriptomic results first revealed initial dysregulations under microplastic stress, increasing energy–metabolic activity and suppressing detoxification-associated pathways on day 3, followed by downregulated gut epithelial maintenance and anti-inflammatory responses by day 7. During this process, opportunistic bacterial taxa such as Edwardsiella and the microbial antioxidant biosynthesis pathway can be enriched transiently. The limited structural damage and modest microbiome alterations observed after acute exposure, however, may suggest partial resilience of the host gut and microbiome. This study demonstrates microplastic-induced gut impairment and host–microbiome responses to acute polyester microplastic stress, providing evidence to enable better characterization of the gut health risks associated with microplastic contamination. Full article

Salmonella primarily affects the gastrointestinal tract, causing local and systemic symptoms. Fucoidan exhibits therapeutic potential against Salmonella-induced pathology; however, the influence of its molecular weight on efficacy remains poorly understood. In this study, low-molecular-weight fucoidan from Undaria pinnatifida (LUPF) was prepared and characterized, and its protective effects against Salmonella infection were evaluated in a mouse model. LUPF effectively mitigated Salmonella-induced multiple organ damage by preserving mucin secretion and tight junction protein expression. Metabolomics analysis further demonstrated that LUPF normalized Salmonella-induced metabolic disturbances, thereby reducing systemic dysfunction. Mechanistically, LUPF suppressed inflammation by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, while alleviating oxidative stress through activation of the Nrf2 pathway. In addition, LUPF restored gut microbiota homeostasis by reducing Proteobacteria levels, improving the Bacteroidota/Firmicutes ratio, enriching beneficial taxa, and enhancing short-chain fatty acid production. In vitro experiments further revealed that LUPF attenuated Salmonella-induced inflammation by modulating macrophage polarization. Collectively, these results suggest that LUPF has promising potential as a prebiotic candidate for reducing the risk of Salmonella-associated diseases. Full article

Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPR^mt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPR^mt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPR^mt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPR^mt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I–V. AAV9-mediated overexpression of HSF1 reactivated the UPR^mt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPR^mt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPR^mt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPR^mt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1–UPR^mt axis as a potential therapeutic target. Full article

Background: Postbiotics, including cell-free supernatants and their fractions, have emerged as a safe and effective alternative to live probiotics for managing intestinal inflammation. This study investigated the protective effects of low-molecular-weight fractions (<3 kDa) of the probiotic Limosilactobacillus fermentum CECT5716 (LMW-LF) in a murine model of experimental colitis. Methods: Male C57BL/6J mice were orally administered LMW-LF for 10 days prior to colitis induction with 3% dextran sodium sulfate (DSS) for 5 days. Colonic damage was assessed via the Disease Activity Index (DAI), histology, and immunofluorescence (Ocln and Ki67). Immune cell populations were analyzed by flow cytometry, while mucosal gene expression and gut microbiota composition were evaluated using RT-qPCR and 16S rRNA sequencing, respectively. Results: LMW-LF administration significantly attenuated clinical symptoms and macroscopic colonic damage. Treatment restored epithelial barrier integrity by upregulating tight junction proteins (Tjp1) and mucin genes (Muc1-3) while normalizing DSS-induced epithelial hyperproliferation. Immunologically, LMW-LF reduced pro-inflammatory monocyte infiltration; downregulated Il6, Tnfa, and Ifng; and promoted an immunoregulatory phenotype by enhancing Ampk expression and partially restoring regulatory T cell (Treg) populations. Furthermore, LMW-LF reshaped the gut microbiota by increasing alpha diversity and promoting the enrichment of beneficial taxa, specifically Akkermansia muciniphila, which correlated with improved mucus layer preservation. Conclusions: LMW-LF is an active fraction acting across the host–microbiota axis. By integrating epithelial protection, immunomodulation, and microbial reshaping, it represents a promising dietary strategy for the management of Inflammatory Bowel Diseases. Full article

The red sea urchin Loxechinus albus is a species of high commercial importance in Chilean aquaculture, whose performance is strongly influenced by environmental conditions such as temperature. The gut microbiota plays a central role in host physiology; however, its interaction with stress-induced molecular responses remains poorly understood. This study evaluated the effects of thermal stress on food consumption, gut microbial composition, oxidative status, and immune- and stress-related gene expressions in L. albus gut. Sea urchins were exposed to control (16 °C) and elevated temperature (22 °C) conditions for 7 and 14 days. Gut microbiota was characterized using 16S rRNA sequencing, while oxidative damage to DNA and proteins was quantified. Gene expression analyses targeted markers of apoptosis (casp3, casp10, bak1), cellular growth (mtor, raptor), stress response (hsp70), and immune regulation (nfκb, foxo). Thermal stress induced a marked reduction in microbial alpha diversity and promoted a shift toward opportunistic taxa. Heat-stressed individuals exhibited significantly increased oxidative DNA damage, whereas protein oxidation remained unchanged. Gene expression analyses revealed early upregulation of casp3, casp10, nfκb, foxo, and hsp70, suggesting activation of apoptotic, immune, and stress-response pathways. In contrast, bak1, mtor, and raptor showed limited or no significant modulation. These findings demonstrate that thermal stress disrupts host–microbiota homeostasis and induces oxidative and molecular responses in L. albus. This integrative response provides insight into mechanisms underlying physiological performance under thermal stress, with important implications for aquaculture sustainability. Full article

Radiation-induced intestinal injury (RIII) is a common complication of tumor radiotherapy, significantly impacting patients’ quality of life and posing challenges for developing effective medical countermeasures. This study investigated the reparative effects of the traditional Chinese medicine Pyrrosia petiolosa (Christ) Ching on radiation damage through in vivo and in vitro models. By integrating gut microbiota and untargeted metabolomics analyses, it elucidated the multidimensional mechanisms through which P. petiolosa regulates the microbiome as well as metabolic homeostasis. In vitro experiments demonstrated that P. petiolosa effectively suppressed radiation-induced inflammatory factors (IL-6, TNF-α, and IL-1β) and alleviated radiation-induced oxidative stress (MDA, GSH, and SOD). In vivo models further confirmed that P. petiolosa significantly alleviated radiation-induced intestinal inflammation and leukopenia, while protecting the structural and functional integrity of mouse small intestinal crypt villi. Mechanistic studies revealed P. petiolosa reshaped the gut microbiota by promoting enrichment of beneficial bacteria such as Bacteroides, concurrently restoring the homeostasis of key metabolic pathways, including glutathione, glycerophospholipids, and the tricarboxylic acid cycle. Analysis of the microbiome–metabolome interaction network revealed that treatment with P. petiolosa altered the correlation patterns between gut microbiota and fecal metabolites, including potentially beneficial bacteria and metabolites associated with inflammatory and oxidative stress responses. These findings suggest that microbiome–metabolome remodeling may contribute to the protective effects of P. petiolosa against radiation-induced intestinal damage. Overall, this study provides preliminary evidence that P. petiolosa may alleviate acute radiation-induced intestinal damage through anti-inflammatory and antioxidant effects accompanied by changes in gut microbiota and metabolic homeostasis, while identifying candidate targets for future functional validation. Full article