Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice.

Structural characterization of κ-carrageenan by acetylation modification and its effect on intestinal inflammation.

Ursolic acid modulates gut microbiota and metabolites to enhance Treg/Th17 balance and intestinal health in broilers.

Effect and mechanism of Rabdosia rubescens on ulcerative colitis: Network pharmacology combined with in vivo experiments.

With the evolution of dietary habits and the widespread application of radiation therapy, high-salt diet (HSD) and irradiation (IR) have become significant public health concerns. This study aims to investigate the protective effects of melatonin (MLT) against multi-organ damage induced by HSD combined with whole-abdominal irradiation (WAI), with a focus on its gender-specific mechanisms. Using a C57BL/6 J mouse model of HSD and IR injury, we employed a multi-omics approach to evaluate MLT's therapeutic effects. Results demonstrated that both oral and intraperitoneal administration of MLT significantly mitigated HSD and WAI-induced damage to renal and intestinal tissues while restoring expression of intestinal tight junction proteins and mucin-2 (MUC2), which is the main intestinal mucin forming the mucus barrier. Further investigations revealed that MLT showed sex-dependent associations with the gut microbiota-metabolite axis. Under HSD conditions, it primarily regulates microbial balance via the tryptophan metabolic pathway, whereas post-IR exposure, its regulation shifts toward specific metabolites. Additionally, MLT alleviates cognitive impairment. These findings provide crucial experimental evidence for developing personalized radiation protection strategies.

Chicory polysaccharide alleviates hypoxia-induced gut dysbiosis and cognitive deficits in mice via IL-6/IL-6R/STAT3-mediated anti-inflammatory mechanisms.

Disruption of goat airway epithelial barrier function by caprine parainfluenza virus type 3 infection in an ALI model.

Preventive effects of GABA-producing postbiotics derived from Levilactobacillus brevis against chronic sleep deprivation-induced gut-brain axis dysfunction, neuroinflammation, and behavioral impairments in mice.

Background: Compared with lactic acid-producing probiotics, spore-producing probiotics such as Bacillus subtilis (BS) and Bacillus natto (BN) exhibited superior metabolic capacity and stress resistance and are more suitable for industrial applications. However, limited understanding of their nutritional and intestinal health mechanisms has constrained their food potential. Objectives: This review systematically expounded on the ‘triple mechanism’ of BS and BN and their effects on intestinal nutrition, immunity and metabolism benefit for the first time. Methods: We searched PubMed, Scopus, Web of Science, and Google Scholar for studies on livestock, model organisms, and human research from 2000 to 2025. After evaluating relevance and eligibility, 115 articles were included. Results: Firstly, by secreting various digestive enzymes, BS and BN directly enhanced the small intestine digestive and absorptive efficiency and promoted animal growth. In particular, BN significantly increases calcium absorption in postmenopausal women. Secondly, as the antigen carrier that induced intestinal mucosal immunity, BS and BN enhanced the host’s defense ability by strengthening the expression of tight junction proteins, mucins, and inflammatory factors and bidirectionally regulated constipation and acute diarrhea in the human body. Thirdly, they reshaped the structure of the intestinal microbiota and their metabolic profile in the form of the gut–liver/gut–adipose axis, including enriching beneficial bacteria, activating lipid metabolism pathways such as PI3K/AKT and AMPK/SREBP, and regulating liver targets such as PPAR and CD36, thereby reducing insulin resistance and liver injury and maintaining overall metabolic homeostasis. Conclusions: Bacillus subtilis and Bacillus natto mediated their probiotic benefits through a gut-centric, multi-system regulatory strategy, involving nutrient utilization, immune homeostasis, and microbial–host metabolic interactions. This integrated mechanism provided a robust foundation for their targeted application in functional formulations and fermented food science.

Ulcerative colitis (UC) presents considerable challenges in clinical treatment due to its multifaceted and complex nature. Efficacious therapy technique in developing an oral formulation that can encapsulate and deliver therapeutic drugs directly to the colon to diminish intestinal inflammation and restore the impaired intestinal barrier is of great interest. Herein, we developed a supramolecular hydrogel platform composed of 2-hydroxypropyl-β-cyclodextrin/chitosan in which curcumin and berberine (HCD/CH-CUR-BBR) are loaded in the hydrophobic cavity of HP-β-CD. BET surface area was measured to be 198.3 m2g- 1 with a pore diameter of 3.56μm which improved in vitro drug release. The results demonstrate that the HCD/CH-CUR-BBR hydrogel leverages pH sensitivity to achieve sustained drug release in the colon while promoting targeted delivery to colonic tissues. Interestingly, in vitro and in vivo evaluation confirms that HCD/CH-CUR-BBR hydrogel formulation alleviates the progression of UC via downregulating IL-6 and TNF-α expression. Subsequently, in vivo anti-colitis investigation demonstrated notable enhancement in tight junction protein expression, underscoring anti-inflammatory efficiency of CUR and BBR loaded HCD/CH hydrogel. These findings indicate that the HCD/CH hydrogel infused with CUR and BBR displayed potential as an effective targeted drug delivery strategy for UC treatment.

One serious consequence of sepsis that has a direct impact on patient outcomes is intestinal barrier disruption brought on by sepsis. Although the polyphenolic molecule resveratrol (RE) is well-known for its anti-inflammatory and antioxidant properties, it is unknown how it affects the NADPH oxidase 1 (NOX1)/sirtuin 1 (SIRT1) pathway and against intestinal barrier failure by sepsis. This work adopted a lipopolysaccharide (LPS)-treated Caco-2 cell and sepsis mice model (cecal ligation and puncture) to assess the protective effects of RE. We employed quantitative reverse transcription PCR, enzyme-linked immunosorbent assay, histological analysis, immunohistochemistry, and Western blot to assess survival rates, inflammatory cytokine levels, autophagy markers, and intestinal barrier function. The role of NOX1 and SIRT1 in RE-mediated protection was explored through NOX1 overexpression and related molecular analyses. RE significantly improved survival rates in sepsis mice, reduced inflammatory cytokines, and restored intestinal barrier function. RE reversed the increase of NOX1 and the decrease of SIRT1 observed in sepsis. Histological analysis showed that RE protected the intestinal structure, maintained the expression of tight junction proteins, and alleviated intestinal damage. In LPS-treated Caco-2 cells, RE inhibited inflammation, autophagy suppression, and reactive oxygen species (ROS) production. NOX1 overexpression partially reversed the protective effects of RE. By modifying the NOX1/SIRT1 signaling pathway, RE guards against intestinal barrier failure by sepsis. These results underline the critical involvement of the NOX1/SIRT1 pathway in autophagy and inflammation control and imply that RE may be a viable treatment approach for intestinal damage associated with sepsis.

Ginseng (Panax ginseng C. A. Mey.), a traditional Chinese medicine, exhibits spleen-fortifying, anti-inflammatory, and anti-ulcerative colitis (UC) effects. Rice-fried ginseng (RFG), prepared by stir-frying with rice together, yields a marked enrichment of rare ginsenosides, which is hypothesized to enhance its anti-inflammatory and anti-UC effects. Therefore, in this study, the chemical compositions of RFG and sun-dried ginseng (SDG) were systematically compared using LC–MS combined with MS-DIAL, and their protective effects against UC were evaluated using lipopolysaccharide (LPS)-induced Caco-2 cells and a dextran sulfate sodium (DSS)-induced UC mouse model. Rice-frying markedly altered the chemical composition of ginseng, and a total of 64 major compounds were identified, of which 31 increased and 33 decreased after processing. These compositional changes were associated with enhanced anti-inflammatory and immunomodulatory effects of RFG. Consistently, RFG enhanced Caco-2 cell viability, decreased TNF-α, IL-1β, and IL-6, and increased ZO-1, occludin, claudin-1, and E-cadherin. In DSS-induced UC mice, RFG attenuated body weight loss, reduced DAI, increased colon length, and decreased the spleen index, accompanied by improved histopathology, reduced pro-inflammatory cytokine levels, and increased expression of tight-junction proteins (TJPs) in a dose-dependent manner. In addition, RFG ameliorated DSS-induced gut microbiota dysbiosis. Metabolomics and network pharmacology analyses highlighted disturbances in linoleic acid and arachidonic acid metabolism and emphasized the involvement of the PI3K–Akt and NF-κB signaling pathways. Western blotting demonstrated decreased phosphorylation of PI3K, Akt, IKKβ, and NF-κB after RFG intervention. Overall, compared with SDG, RFG showed stronger protective effects in vitro and in vivo, accompanied by improved inflammatory readouts, altered lipid-related metabolites and gut microbiota profiles, and reduced phosphorylation of PI3K, Akt, IKKβ, and NF-κB.

To investigate the therapeutic effect of verbenalin (VE) on Crohn's disease (CD)‑like colitis and the underlying molecular mechanism. Fifty C57BL/6 mice were randomly divided into control group, TNBS group, and low-, medium-, and high-dose VE treatment groups (n=10). Mouse models of CD-like colitis were established in all but the control group by enema with 25 mg/L TNBS dissolved in ethanol, and the mice in VE treatment groups received daily intraperitoneal injections of VE at 5, 10, or 20 mg/kg for 7 days. Cultured colon organoids derived from mouse crypts were exposed to 100 μg/mL lipopolysaccharide (LPS) for 24 h and treated with 5, 10, or 20 μmol/L VE. The therapeutic effects of VE in the mouse models were evaluated by assessing changes in disease activity index (DAI), histopathological scores, and spleen index. In both colonic mucosa of the mouse models and the colon organoids, the levels of inflammatory cytokines, expressions of tight junction proteins, and changes in PI3K-AKT pathway proteins were analyzed, and the regulatory mechanism of VE was verified using the PI3K-AKT agonist 740 Y-P. In TNBS-treated mice, VE treatment significantly reduced DAI, histopathological scores, and spleen index, and mitigated weight loss, colon shortening and bacterial translocation. VE obviously lowered the expression of pro-inflammatory cytokines in colonic mucosa of the mice and the colon organoids, upregulated ZO-1 and claudin-1 expressions, and reduced bacterial translocation. VE significantly downregulated p-PI3K and p-AKT protein expressions, which was reversed by treatment with 740 Y-P. VE inhibits intestinal inflammation and protects intestinal barrier function in mice with CD-like colitis by modulating the PI3K-AKT signaling pathway.

To investigate the molecular mechanism by which veratric acid (VA) ameliorates oxidative stress injury and intestinal barrier dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. Thirty male C57BL/6 mice were randomized equally into control group, DSS model group, and VA treatment group. The mice were assessed for changes in body weight, disease activity index (DAI), colon length, and colonic histopathology. Colonic expressions of TNF-α, IL-6, and IL-10 and oxidative stress markers (SOD, GSH, MDA, and COX-2) were determined using ELISA, and the expressions of tight junction proteins (ZO-1 and claudin-1) and Nrf2/HO-1 pathway proteins were detected using immunofluorescence staining and Western blotting. In Caco-2 cells with H₂O₂-induced oxidative stress, ROS accumulation was examined using flow cytometry and a DCFH-DA probe, and Nrf2 inhibitor (ML385) was used to validate the mechanism of VA for ameliorating oxidative stress. VA treatment significantly alleviated DSS-induced body weight loss, colon shortening and the increase of DAI score of the mice, resulting also in improved crypt structure and increased expressions of ZO-1 and claudin-1 and the number of goblet cells. VA obviously reduced colonic levels of TNF‑α and IL-6, increased the level of IL-10, and reversed DSS-induced decreases in SOD and GSH activity and increases in MDA and COX-2 levels. In H₂O₂-treated Caco-2 cells, VA decreased ROS-positive cell rate and intracellular ROS accumulation, and increased cellular expressions of claudin-1 and ZO-1. Mechanistically, VA promoted the expressions of Nrf2 and the downstream HO-1 protein, and ML385 partially reversed ROS-reducing effect of VA. VA enhances antioxidant defense, inhibits inflammation, and repairs intestinal barrier function in mice with DSS-induced colitis by activating the Nrf2/HO-1 pathway, suggesting a novel strategy for treatment of inflammatory bowel disease.

Hyperlipidemia is a leading global health challenge, limited by the safety liabilities of current pharmacotherapies. Here, we isolated a novel Limosilactobacillus reuteri strain, MacFasB02, from fecal samples of cynomolgus monkeys tolerant to chronic high-fat diet (HFD). This study aimed to systematically evaluate its probiotic properties and therapeutic potential against hyperlipidemia. In vitro, MacFasB02 exhibited robust growth, acid production, and tolerance to acidic and bile environments. In HFD-fed mice, 13-week MacFasB02 administration reduced weight gain, serum triglycerides, low-density lipoprotein cholesterol and total cholesterol, while ameliorating hepatic steatosis and inflammation, as well as restoring intestinal barrier integrity by enhanced villus architecture, goblet cell function, and tight junction proteins expression. Metagenomic analysis revealed gut microbiota remodeling. Transcriptomic profiling coupled with in vivo validation demonstrated upregulation of Apoa1 and Pltp in cholesterol metabolism. Untargeted metabolomics integrated with whole-genome sequencing and supernatant metabolite profiling identified adenosine as a key MacFasB02-derived metabolite in purine metabolism. Consistently, In vitro experiments showed that adenosine reduced lipid accumulation and inflammation in hepatocytes by regulating Apoa1 and Pltp to modulate cholesterol metabolism. Collectively, MacFasB02 exerts dual lipid-lowering and anti-inflammatory effects probably via adenosine-mediated modulation of cholesterol metabolism, promising potential as a live biopharmaceutical agent for hyperlipidemia.

Reduced levels of circulating gonadal hormones in post-menopausal women can negatively affect various physiological functions, including brain and gut deficits. There is an urgent need to find novel strategies to mitigate estrogen-gut-microbiome-brain axis (EGMBA) dysfunction. This study aimed to investigate the effect of fructooligosaccharide (FOS), a non-digestible prebiotic fiber, on estrogen deficiency-induced alterations in the EGMBA using an ovariectomized (OVX) rat model. Adult female SD rats were bilaterally OVX to induce estrogen deficiency and associated EGMBA dysfunction. Rats were administered FOS (50 mg kg-1 p.o.-1) for 28 consecutive days. To assess EGMBA dysfunction, after 28 days, we performed behavioral tests, biochemical estimations (oxidative stress), molecular estimations (inflammatory markers via ELISA), gene expression analysis (HPA axis, monoamine neurotransmission, apoptosis, gut microbiota alterations, & gut barrier integrity via RT-PCR/qPCR), and histopathological analysis. Administration of FOS significantly improved behavioral outcomes (reducing anxiety and depression, and improving memory). FOS also attenuates oxidative stress and inflammatory markers. FOS regulates apoptosis (upregulation of BCL-2 and downregulation of Bax), HPA axis functioning (corticosterone, GR, MR, & CRH), and monoamine neurotransmission (MAO-A & COMT) in the hippocampus of OVX rats. FOS also promoted healthy cell growth and prevented apoptosis. Additionally, FOS restored gut microbial eubiosis, improved mucus secretion (MUC-2), preserved tight junction protein expression (Lipocalin-2, Claudin, & TLR-4), and maintained the colon microstructure. FOS exerts multifaceted protective effects on the EGMBA by modulating gut and brain functions. These findings support its potential as a non-hormonal therapeutic approach for managing postmenopausal complications.

Lacticaseibacillus rhamnosus is commonly used to manage gastrointestinal infections in children, yet its efficacy as a probiotic feed additive for poultry against enteropathogenic bacteria remains insufficiently explored. In this study, a strain L. rhamnosus (CIQ249) was isolated from chicken intestine and evaluated for its ability to enhance intestinal homeostasis and confer resistance against enteropathogens using chicks as animal model. CIQ249 exhibited strong potential for intestinal colonization and high tolerance to gastrointestinal stress, including acid, bile, and osmotic pressure. In vitro, CIQ249 showed effective inhibitory activity against pathogenic bacteria as determined by agar well diffusion assay. During a one-month feeding trial, dietary supplementation with CIQ249 significantly improved the growth performance of broilers. In subsequent experimental challenges, oral gavage administration of CIQ249 conferred protection against E. coli O78 and S. Typhimurium. Furthermore, CIQ249 modulated intestinal immune response by increasing levels of IL-4, IL-10, IFN-γ, and sIgA, while suppressing production of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). It also upregulated expression of tight junction proteins (ZO-1 and Claudin-1), alleviating gut damage induced by pathogenic infections. These findings indicate that CIQ249 is a promising probiotic feed additive that protects chickens from enteropathogenic bacteria by reinforcing intestinal epithelial barrier and enhancing immune homeostasis.

Abstract Immune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. In triple-negative breast cancer (TNBC), an aggressive and generally immune-rich subtype, an immune-cold microenvironment predicts poor prognosis due to a limited response to chemotherapy and immune checkpoint inhibitors. To identify mechanisms regulating immune infiltration in TNBC, we performed spatial transcriptomic analysis comparing immune-enriched versus immune-cold tumors. We reveal that Trophoblast Cell-Surface Antigen 2 (TROP2), a key target of anti-cancer Antibody Drug Conjugates (ADCs), controls barrier-mediated immune exclusion in TNBC through Claudin 7 association and tight junction regulation. TROP2 expression is inversely correlated with T cell infiltration and predicts poor outcomes in TNBC. Loss-of-function and reconstitution experiments demonstrate TROP2 is sufficient to drive tumor progression in vivo in a CD8 T cell-dependent manner, while its loss deregulates expression and localization of multiple tight junction proteins, enabling T cell infiltration. Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via hRS7, the antibody component of the ADC Sacituzumab govitecan (SG), enhances the anti-PD1 response and improves T cell accessibility and effector function. Correspondingly, TROP2 expression is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Thus, TROP2 controls an immune exclusion program that can be targeted to enhance immunotherapy response. Citation Format: B. Wu, W. Thant, E. Bitman, T. Liu, J. Liu, E. Paschalis, B. Patel, C. Nawrocki, K. Xu, L. Nieman, D. Ting, N. Thimmiah, S. Sun, R. Abelman, V. Bossuyt, S. Isakoff, L. Spring, A. Bardia, L. Ellisen. Trop2 remodeling of the immune microenvironment in triple negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-12-29.

Deoxynivalenol (DON), a prevalent mycotoxin in grains and feed, poses a serious threat to animal health by inducing intestinal dysfunction. While some probiotics are known to mitigate DON toxicity, the multifaceted protective effects of Lactobacillus rhamnosus MY-1-a strain with high DON-degradation capacity and a proven safety profile-require comprehensive evaluation. This study aimed to systematically assess the ability of MY-1 to alleviate DON-induced oxidative stress, inflammation, and gut microbiota dysbiosis, and to elucidate its underlying mechanisms. Investigations were conducted in vitro using IPEC-J2 cells and in vivo using a BALB/c mouse model. We examined the effects of MY-1 on cell viability, ultrastructure, oxidative stress markers (MDA, T-AOC), inflammatory cytokines (TNF-α, IL-1α, IL-4), apoptosis-related genes (BAX, Caspase-3, BCL-2), and tight junction protein (ZO-1, Occludin, Claudin-1) expression. Gut microbiota composition was analyzed via alpha (Chao1, Simpson, Shannon) and beta diversity indices. The MY-1 supernatant restored IPEC-J2 cell viability and ameliorated DON-induced ultrastructural damage. MY-1 alleviated oxidative stress by reducing MDA and enhancing T-AOC, while inhibiting pro-inflammatory cytokines (TNF-α, IL-1α) and promoting the anti-inflammatory cytokine IL-4. In mice, MY-1 mitigated DON-induced growth inhibition and intestinal pathological damage, restored tight junction protein expression, and regulated apoptosis-related genes. Gut microbiota analysis showed that MY-1 reversed DON-induced dysbiosis, restoring alpha diversity and beta diversity structure, and modulated the abundances of dominant genera such as Bacteroides and Dubosiella. This study demonstrates that Lactobacillus rhamnosus MY-1 exerts comprehensive protective effects against DON-induced intestinal toxicity through integrated mechanisms, including direct detoxification, antioxidant and anti-inflammatory activities, and microbiota modulation. These findings underscore the value of MY-1 as a well-characterized probiotic candidate for mitigating mycotoxin effects in animal production.

PGK1 contributes to blood-brain barrier integrity via PI3K-AKT-mTOR pathway in early pneumococcal meningitis.