The integrity of the intestinal mucosal barrier is essential for maintaining normal gut physiology, and its disruption is associated with a wide range of conditions, including trauma- and burn-related intestinal injury, which remain difficult to manage clinically. Intestinal organoid-on-a-chip systems have emerged as advanced in vitro models that reproduce key features of the intestinal microenvironment and physiological function. These systems have shown promise for studying mucosal injury and repair, assessing therapeutic strategies, and supporting translational research. This review summarizes the basic principles of intestinal organoid-on-a-chip technology and examines its use in modeling intestinal barrier function, inflammatory responses, drug screening, regenerative approaches, and trauma-related barrier repair. It also reviews recent progress in preclinical studies, considers potential applications in gastrointestinal research, and discusses current technical challenges, particularly those related to scalability and reproducibility. Future directions for the development of next-generation systems are also outlined. With the continued integration of advances across disciplines, these platforms may provide useful tools for studying and treating disorders involving the intestinal mucosal barrier, especially in the context of trauma and burns.
As natural bioactive macromolecules isolated from various berries, Berry polysaccharides (BPs) possess excellent biocompatibility, low toxicity and diverse health-promoting properties, which has garnered extensive interest in functional food and pharmaceutical research. Nevertheless, imperfect large-scale manufacturing processes, ambiguous structure-activity relationship (SAR) and limited metabolic research substantially impede their industrial transformation and practical application. This review systematically summarizes recent research advances on BPs, clarifies their preparation technologies, multifunctional bioactivities, molecular mechanisms, SAR rules, pharmacokinetic profiles and safety assessment, and highlights the cutting-edge technologies, so as to offer theoretical support for subsequent development and utilization of BPs. This comprehensive review was conducted to integrate and critically appraise the latest research progress on BPs, covering innovative preparation technologies, biological function exploration, structural-activity correlation analysis, pharmacokinetic profiles and cutting-edge interdisciplinary translational applications. Peer-reviewed literatures focusing on the extraction and purification, bioactivity evaluation, molecular mechanistic exploration, SAR analysis, pharmacokinetics and toxicological assessment of BPs were rigorously retrieved, screened and summarized for synthetic discussion. Novel eco-friendly extraction techniques, including ultrasonic-, microwave-, enzyme-assisted extraction and membrane separation are progressively replacing traditional extraction strategies. Berry polysaccharides display diverse bioactivities such as anti-inflammation, immunomodulation, hypoglycemia, hypolipidemia, neuroprotection and gut microbiota regulation via NF-κB, PI3K/Akt, MAPK, Keap1-Nrf2 signaling pathways and short-chain fatty acid metabolism. Meanwhile, SAR studies identify the molecular weight, glycosidic linkage, branching patterns and spatial conformation as critical factors dominating their bioactivity and bioavailability. BPs exhibit low oral bioavailability but favorable safety profiles, relying primarily on intestinal microbiota metabolism. Notably, artificial intelligence, multi-omics and nanotechnology greatly accelerate the comprehensive research on BPs. This review systematically summarizes current research progress and application prospects of berry polysaccharides (BPs). It deepens the understanding of their structure-function correlations and molecular mechanisms, offering valuable references for the rational development and translational application of BPs in functional foods, pharmaceuticals and health-benificial products.
To evaluate whether full-thickness intestinal biopsies performed with an automated needle-core device, without closure of the biopsy site, maintain adequate intestinal integrity in dogs and cats. This experimental study consisted of ex vivo testing on small intestinal segments from fresh canine and feline cadavers, and in vivo testing in dogs and cats undergoing enterectomy for unrelated indications. Full-thickness biopsies were performed using a 16-gauge automated needle-core device, with biopsy sites left unsutured. Intraluminal pressure was progressively increased using methylene blue-stained saline, and the initial leakage pressure (ILP) was recorded at first visible evidence of leakage. Cadaveric and in vivo ILP were compared to each other and to the reported maximal physiological intraluminal pressure of 25 mmHg. Thirty-nine cadaveric intestinal segments from seven animals were evaluated. The mean cadaveric ILP was 20.7 mmHg (95% CI [5.9-35.5 mmHg]), with leakage observed below 25 mmHg in 33 of them. In vivo ILP was measured in 12 patients (8 dogs, 4 cats), yielding 23 measurements. The mean in vivo ILP was 85.66 mmHg (95% CI [55.53, 115.78]), significantly exceeding the reference value of 25 mmHg, and all measurements remained above 26 mmHg. Cadaveric leakage pressures were markedly lower than in vivo measurements, suggesting that cadaveric models may be poorly suited for evaluating intestinal pressure. In contrast, unsutured needle-core biopsy sites in live dogs and cats tolerated pressures above reported maximal physiological levels, immediately after biopsy. These findings suggest that the immediate risk of leakage at small (1.3-mm) unsutured biopsy sites is low; however, because healing and longer-term integrity were not evaluated, the necessity of routine closure cannot be established from these data. Further studies are needed to evaluate long-term safety and applicability in diseased intestines.
Schistosomiasis japonica is a parasitic disease leading to liver cirrhosis. China's "fishermen going ashore" policy divides patients with schistosomiasis liver fibrosis into two groups: those near the infected waters and those inland far from the infected water. This study aims to compare the differences in intestinal flora between two groups from the perspective of intestinal flora, and provide a basis for future prevention and control priorities. This study collected feces and basic information of patients with Schistosoma japonicum cirrhosis living near infected water and living on land. The characteristics of intestinal flora of the two types of patients were compared by 16sRNA sequencing technology. The infected water contact group and the terrestrial living group showed significant differences in intestinal flora characteristics: the former showed dominance of Firmicutes, high α-diversity, enrichment of butyrate-producing bacteria (such as Blautia), and enhanced environmental adaptability; the latter showed an imbalanced state with increased Proteobacteria and reduced α-diversity, accompanied by abnormal lipid metabolism and barrier function damage.
Inflammatory bowel disease (IBD) is a chronic and progressive disorder of the digestive tract, including Crohn's disease and ulcerative colitis. Over the last decade, IBD has been extensively studied due to its association with dysregulated intestinal microbiota, increased mucosal permeability, and immune imbalance. Despite available pharmacological treatments, there is no definitive cure. Mucosal healing (MH) has emerged as a crucial therapeutic target, as it aims to restore the integrity of inflamed mucosae and is associated with improved clinical outcomes. However, most clinical studies rely primarily on clinical indices rather than direct endoscopic or histologic assessment of MH, and the optimal vitamin D (VD) dosing required to achieve true MH remains unclear. This review aims to examine the diverse functions of VD in modulating pathways relevant to MH within the context of IBD, highlighting its role in immune modulation, intestinal barrier integrity, and gut microbiota composition, and to discuss its potential therapeutic value in IBD management. Relevant experimental, translational, and human clinical studies focusing on VD status, supplementation, and mechanisms related to MH, immune regulation, and intestinal barrier function in IBD were considered. MH involves epithelial restitution, cell proliferation, and differentiation, and its achievement has been associated with reduced symptoms, lower relapse rates, and decreased need for surgical interventions. Beyond its traditional role in bone health, VD plays a critical role in preserving intestinal barrier integrity and regulating immune homeostasis. While biological evidence indicates that VD modulates immune responses, enhances tight junction integrity, and influences gut microbiota composition, clinical data primarily support its role in improving clinical and biochemical disease activity rather than definitively inducing mucosal repair. This review highlights VD as a relevant immunomodulatory and barrier-protective factor with potential complementary value in the clinical management of patients with IBD. Vitamin D and intestinal healing in inflammatory bowel disease Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic condition that causes inflammation in the digestive tract. People living with IBD often experience abdominal pain, diarrhea, fatigue, and reduced quality of life. Although several treatments exist, there is currently no cure. One important treatment goal is “mucosal healing,” which means repairing the lining of the intestine and reducing inflammation to prevent relapses and complications. Vitamin D is best known for its role in bone health, but growing evidence shows that it also plays an important role in immune function and gut health. Many patients with IBD have low vitamin D levels, and this deficiency has been linked to more severe disease, increased hospitalizations, and higher relapse rates. This review summarizes current research on how vitamin D may help promote mucosal healing in IBD. Studies suggest that vitamin D helps strengthen the intestinal barrier, reduce harmful inflammation, and support a balanced gut microbiota. It also regulates immune responses and promotes the production of protective molecules that help repair intestinal tissue. Clinical studies indicate that vitamin D supplementation may reduce disease activity and improve quality of life in patients with IBD. However, optimal dosing remains unclear, as vitamin D levels can vary depending on factors such as diet, sun exposure, disease severity, and individual metabolism. Overall, maintaining adequate vitamin D levels appears to be a safe and promising complementary strategy for improving outcomes in patients with IBD. Future research is needed to determine the best supplementation strategies and to better understand how vitamin D contributes to long-term intestinal healing.
Early-life sex identification technologies are making sex-specific management increasingly feasible in broiler production, yet limited information exists on how males and females differ in the development of their gut ecosystem. While sex-related variation in growth rate and endocrine physiology is well established, much less is known about potential differences in gut morphology, barrier function, microbiota assembly, and intestinal gene expression during the starter period, where early performance divergence between males and females begins to emerge. A clearer understanding of these early-life processes is essential to refine sex-specific nutrition and management strategies. Therefore, this study investigated sex-related differences in gut morphology, intestinal permeability, microbiota composition and predicted functionality, as well as ileal gene expression related to nutrient transport, barrier function, immune response, and metabolic signaling in broilers at 7, 14, and 21 days of age. Body weight followed a typical early-life pattern and differed between sexes only at d 21, when males were heavier. Gut morphology matured similarly in both sexes, whereas gut permeability declined with age and was lower in males at d 20, suggesting a slightly tighter intestinal barrier. Microbiota structure was predominantly shaped by age, but sex-related divergence emerged with maturation from d 14 onward, especially in the cecum: males were enriched in strict anaerobic fermenters and carbohydrate-degradation/short-chain fatty acid (SCFA)-related pathways, while females showed higher abundance of Romboutsia, Flavonifractor, and other taxa linked to proteolytic metabolism and the degradation of aromatic amino acid-derived compounds. Gene expression was mainly driven by age, yet consistent sex-specific transcriptional signatures were revealed. Males were more associated with nutrient transport (e.g., SLC15A1, SLC30A1, SLC5A1) and epithelial functional maturation profiles (e.g., CDX) over time, whereas females were more associated with tight-junction integrity (e.g., OCLN) and amino-acid sensing/transport markers (e.g., T1R1, SLC3A1). Cecal SCFA concentrations were measured at d 21, yet no differences were found. Overall, gut development was largely age-driven, but sex-specific differences in barrier function, microbiota composition and function, and epithelial gene expression emerged with maturation, without differences in gut morphology or luminal SCFA concentrations.
Antimicrobial resistance is accelerating the search for sustainable alternatives to growth-promoting antibiotics (GPAs) in tropical poultry farming. The objective of this study was to evaluate three indigenous strains of lactic acid bacteria (LABs): Enterococcus faecium JK96, Pediococcus acidilactici JK148, and Lactobacillus pentosus JK151, isolated from the gastrointestinal tract of free-range, native Ivory Coast chickens, as probiotic candidates for commercial broiler production. To this end, in a 42-day completely randomized trial, 480 one-day-old Cobb 500 broiler chicks were divided into six treatment groups: three individual probiotic strains, a combination of several strains (1:1:1), an antibiotic growth promoter (Tylo-dox), and an untreated control group. Each group consisted of two pens of 40 chickens each. Freeze-dried probiotic powders (viable cell count: ~1.0 × 10¹⁰ CFU/g) were administered daily in drinking water at a rate of 0.5 g per 10 L. Growth performance, blood biochemical parameters, and intestinal microbiota were assessed in 42-day-old chickens. The results of this study showed that probiotic supplementation significantly improved average daily gain (ADG) and feed conversion ratio (FCR) compared to the control and antibiotic-treated groups. The Lactobacillus pentosus JK151 strain achieved the highest ADG on day 28 (108.27 g/day vs. 83.83 g/day in the control group), maintained an FCR below 2.0 throughout the finishing period, and exhibited no cumulative mortality, compared to 5.0% in the antibiotic-treated group. No significant differences were observed in serum biochemical parameters (glucose, total protein, albumin, triglycerides, cholesterol, uric acid, alkaline phosphatase) or carcass characteristics between treatments (p > 0.05), thus confirming the physiological safety of all tested strains. All probiotic groups significantly reduced the intestinal bacterial load of Escherichia coli (1.38-9.54 × 10⁷ CFU/g) compared to the untreated control group (9.81 × 10⁹ CFU/g) and the antibiotic-treated group (1.10 × 10⁹ CFU/g), without significantly altering the total mesophilic aerobic flora or lactic acid bacteria populations. Notably, the antibiotic-treated group exhibited a higher bacterial load of E. coli than the control group, These results demonstrate that indigenous strains of lactic acid bacteria, in particular L. pentosus JK151, are effective, safe and locally adapted alternatives to growth-promoting antibiotics (GPAs) for sustainable broiler chicken production in Côte d'Ivoire.
In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.
Disruption of host-microbiota homeostasis is a fundamental hallmark of inflammatory bowel disease (IBD) pathogenesis. Host epigenetic modifications and corresponding alterations in gene expression levels can impact the composition of gut microbes. SET domain containing 2 (SETD2) is a critical epigenetic regulator with established tumor-suppressive roles, but its function in intestinal microbial ecology and colitis progression remains unexplored. We aimed to investigate the specific role of SETD2 in maintaining gut microbial homeostasis and modulating colitis progression. RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and cleavage under targets and tagmentation sequencing (CUT&Tag-seq) were conducted on colonic epithelial cells from intestinal epithelial cell-specific SETD2 knockout (Setd2vil-ko) mice to identify key mediators contributing to colitis development. Faecal samples underwent 16S rRNA sequencing and non-targeted metabolomics analysis to characterise microbial dysbiosis and metabolic perturbations. Molecular experiments and faecal microbiome transplantation experiment were conducted to explore and validate the role of SETD2 in colitis development. SETD2 deficiency induced overproduction of Reg3 lectins and disrupted gut microbiota composition. Beneficial commensal bacteria were depleted and dysregulated metabolites were accumulated in Setd2vil-ko mice. Supplementation with healthy-like gut microbiota significantly ameliorated the exacerbated colitis induced by SETD2 deficiency. Our findings uncover a previously unrecognised role for SETD2 in maintaining microbial homeostasis, offering new mechanistic insights into how epigenetic regulation preserves intestinal homeostasis and suggesting novel therapeutic avenues for IBD.
The temporal, spatial, and cellular diversity of the small intestinal epithelium during the postnatal period, a critical time window that accompanies the transition from placental energy supply to enteral feeding, and the establishment of the enteric microbiota and postnatal immune maturation, has not been systematically investigated. Here, we used laser capture microdissection and bulk RNA-Seq, proteomics, and single cell RNA-Seq to analyze the total, organ site, crypt- and villus-specific intestinal epithelium of specific pathogen-free, germ-free, and Salmonella-infected mice during the postnatal period. We identified key temporal and organ-site specific expression patterns that revealed a weak effect of the microbiota but strong influence of developmental regulators during early life. We also determined age-dependent signaling pathway and transcription factor activity and characterized age- and cell type-specific developmental trajectories revealing a distinct compartmentalized maturation process along the proximal-to-distal length and crypt-villus axis and a discontinuous appearance of goblet/Paneth cell and absorptive enterocyte transcriptional profiles. Finally, we described the cell type-specific response to neonatal enteric infection. Taken together, our findings identify the epithelium as an integral element in the maturation of postnatal mucosal tissues and in the establishment of host-microbe homeostasis.
Invasive fungal infections are life-threatening complications in immunocompromised and critically ill patients. Invasive candidiasis may arise from endogenous fungal reservoirs, particularly under conditions of intestinal barrier disruption. Although conventional antifungal agents remain the therapeutic foundation, their clinical use is increasingly challenged by the emergence of resistant fungal pathogens, such as Candida auris. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microorganisms. Beyond their well-established applications in the food industry, bacteriocins have attracted increasing attention in recent years for their antifungal properties. In this review, we provide an overview of bacteriocins with reported antifungal activity and summarize their underlying mechanisms. In addition, we discuss the potential protective effects of bacteriocins on the microbial, mechanical, chemical, and immune barriers of the intestine. Finally, we evaluate the potential clinical applications of these bacteriocins, along with future challenges and research directions related to invasive fungal infections.
As a highly reproductive meat sheep breed in China, Hu sheep is an important economic group in ruminant animal breeding. However, research on its intestinal microbiomes under the background of diarrhea and antibiotic treatment remains relatively limited. This study investigated the intestinal microbiota of Hu sheep lambs in the preliminary stage of diarrhea (group DM), the late recovery stage of diarrhea (group DL), and the healthy stage (group H). Diseased individuals (groups DM and DL) were treated with a combination of Shuanghuanglian, Cefazolin, Lincomycin, and Dexamethasone (0.2 mL dosage). To characterize the intestinal microbiota, fecal samples were collected from all groups, and metagenomic sequencing was performed. Using metagenomic binning tools and co-assembly methods, we reconstructed 482 high-quality non-redundant metagenome assembled genomes (MAGs). Among these MAGs, 70% belong to the phyla Bacillota, Bacteroidota, and Pseudomonadota, highly consistent with the typical structure of intestinal microbiota in ruminants. Functional annotation revealed that the genes encoding carbohydrate-active enzymes (CAZymes) are more abundant in Bacillota and Bacteroidota, which supports the degradation and energy metabolism functions of Hu sheep on fibrous feed. During the preliminary stage of diarrhea, the virulence genes carried by symbiotic bacteria such as Lachnospiraceae, Acutalibacteraceae and Bacteroidaceae were enriched. Although diarrhea symptoms alleviated during the late recovery stage of diarrhea, the combined use of multiple antibiotics led to the continuous enrichment of antibiotic resistance genes (ARGs) related to lincosamides and cephalosporins. The average abundance of cephalosporin-related ARGs in group DL was significantly higher than that in group DM and H, indicating a risk of residual ARGs. Microbial diversity analysis showed that there was no significant overall difference in MAGs between group DM and H, but both groups showed significant differences compared to group DL, suggesting that antibiotic driven clearance of sensitive bacteria is the core driving force. Moreover, our study shows that the abundance of the zoonotic pathogens Barnesiella and Campylobacter significantly increased in the diarrhea group (p <  0.05), and they carry 567 and 382 virulence genes, respectively. Their pathogenicity is regulated by the dynamic changes in the host intestinal microbiota. This study not only expands the genomic database of ruminant intestinal microorganisms but also provides a key theoretical basis for formulating intestinal microecological regulation strategies and optimizing diarrhea treatment regimens for Hu sheep.
Human norovirus (HuNoV) is a major cause of acute viral gastroenteritis. Although it can be replicated in vitro using human intestinal enteroids (HIEs), generating high-titer viral laboratory stocks remains challenging due to low infection and passage efficiencies. Interferon response and chemokine signaling may be key host pathways that restrict efficient HuNoV replication. Here, we evaluated the effect of their inhibitors, ruxolitinib-a Janus kinase (JAK) 1/JAK2 inhibitor-and TAK-779-a C-X-C motif chemokine receptor 3 (CXCR3)/C-C motif chemokine receptor (CCR) 5/CCR2 antagonist-on HuNoV replication in wild-type jejunal HIEs. TAK-779 increased GII.17 HuNoV replication by 2.3- and 6.0-fold at 48 and 96 h postinfection (hpi), respectively, compared with the DMSO-treated control. In contrast, ruxolitinib alone did not affect viral replication. Notably, simultaneous treatment with these compounds further enhanced GII.17 replication by 6.0- and 10.7-fold at 48 and 96 hpi, respectively, which enabled serial passaging. These findings imply that the simultaneous suppression of these pathways potentially benefits GII.17 HuNoV replication.
Gastrointestinal parasites affect the health and productivity of guinea pigs. This study aimed to determine the frequency of gastrointestinal parasite infection among naturally dead guinea pig carcasses collected from family-commercial farms in two high-Andean communities in southern Peru, to explore associated risk factors, and to quantify the parasite burden. A total of 223 rectal samples obtained from guinea pig carcasses that had died naturally were analyzed by flotation and McMaster techniques. The study used convenience sampling of carcasses from farms with at least 200 animals. Therefore, the frequency of infection estimated in the examined carcasses should not be extrapolated to the living guinea pig population. The overall infection frequency was 80.27% (95% CI 75.05-85.49). Paraspidodera uncinata (53.81%), Eimeria spp (34.98%), Capillaria spp (24.66%), Trichuris spp (13.90%), and strongylid-type nematodes (4.48%) predominated. Among infected carcasses (n = 179), 49.16% had mono-infection, 38.55% had bi-infection, 11.17% had tri-infection, and 1.12% had four parasites. In univariate analyses, the stage increased the probability of P. uncinata (OR = 2.33, p = 0.036), the rainy season increased the odds of P. uncinata (OR = 1.75, p = 0.038), and Eimeria spp (OR = 3.09, p < 0.001), and the Ccuyo community showed higher odds for Eimeria spp infection than Mamuera (OR = 2.48, p = 0.002), whereas the adult stage was protective (OR = 0.16, p < 0.001). Parasite burden varied widely, with Eimeria spp reaching extreme values (≈ 1.06 × 107 OPG). These findings support strengthened surveillance and integrated parasite control in young guinea pigs and during rainy season in the evaluated farms, while highlighting the need for future multivariate analyses that account for clustering by farm and include live-animal populations.
Plant-derived extracellular vesicles are promising candidates for oral drug delivery, yet their clinical translation is hindered by limited targeting precision and inconsistent systemic absorption. While surface engineering can enhance tissue accumulation, strategies that preserve biocompatibility and enable scalable production remain limited. Here, we introduce boiling as a simple thermal processing approach that structurally reconfigures ginger extracellular vesicles (GEVs) into functionally enhanced, thermally reassembled GEVs (T-GEVs). The surface architecture of T-GEVs is enriched with key vesicle trafficking regulators, including V-type proton adenosine triphosphatase subunit G, ARF1, and β-adaptin-like protein. This specific composition drives their tissue-specific accumulation in the intestine and liver and potentiates clathrin-dependent cellular uptake in intestinal cells by 8.57-fold. Beyond superior intrinsic anti-inflammatory activity through NLRP3 inflammasome suppression, T-GEVs function as an efficient oral delivery platform. When loaded with tumor necrosis factor-α (TNF-α) small interfering RNA, they enable a synergistic therapy that combines innate anti-inflammatory activity with targeted gene silencing of TNF-α, showing potent efficacy in colitis. Our findings position boiling as a natural strategy for enhancing the bioactivity and targeted oral delivery potential of GEVs.
This paper aims to evaluate the feasibility of clinical application of high-pressure Schisandrae Chinensis Fructus decoction pieces(HPSCH) compared with that of traditional Schisandrae Chinensis Fructus decoction pieces(SCH), based on the efficacy of mice with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. The optimal preparation process of HPSCH was investigated by using schisandrin content and total extractive yield as indices. After one week of adaptive feeding, C57BL/6 mice were assigned to a normal control group, while the remaining mice were fed an HFD for eight weeks to establish the NAFLD mouse model. After being successfully modeled, the mice were divided into a blank control group, blank administration group, simple model group, fenofibrate group, SCH group, and HPSCH group. All groups were administered by intragastric administration for four weeks. Body weight changes of mice were recorded, and liver indices were calculated. The levels of blood lipid and liver function index in the serum of mice were measured. Hepatic histopathological changes were observed by using hematoxylin-eosin(HE) staining and oil red O staining. Mice's feces were collected, and the 16S rDNA high-throughput sequencing method was employed to analyze changes in the gut microbiota of mice. Untargeted lipidomic analysis of the liver was conducted by using liquid chromatography-mass spectrometry(LC-MS), and principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were adopted to screen and identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used to perform relevant pathway analysis. Integrated analyses of gut microbiota and differential metabolites were performed to compare the similarities and differences in efficacy of HPSCH and SCH. The results show that both the HPSCH group and SCH group exert similar effects on biochemical indices in serum and hepatic pathological changes, lipid metabolism can be regulated, and liver injury in NAFLD mice can be improved. The two groups show similar changes in microbial abundance, trending toward the blank control group and maintaining intestinal homeostasis. Compared with those of the simple model group, the differential metabolites and metabolic pathways of both the HPSCH group and SCH group show similarity, and the differential metabolites are mainly triglycerides, diglycerides, phosphatidylcholines, phosphatidylglycerols, and so on. Metabolic pathways include glycerophospholipid metabolism, choline metabolism, retrograde endocannabinoid signaling, thermogenic lipolysis, and so on. This indicates that HPSCH and SCH share common advantages in improving hepatic function in mice and achieve comparable effects. HPSCH can improve blood lipid and liver function indices in NAFLD mice, attaining the therapeutic effect through the regulation of gut microbiota and lipid metabolism. Notably, HPSCH achieved the same efficacy as SCH at half the conventional dose, demonstrating its feasibility for clinical application. Moreover, the application of HPSCH may contribute to the conservation of medicinal resources.
This study investigated the effects of replacing soybean meal (SBM) with black soldier fly larvae meal (BSFL) on the performance, carcass yield, blood biochemistry, hematology, and organ histology of broiler chickens. A total of 250 one-day-old Ross chicks were randomly allocated into five dietary treatments, with 5 replicates of 10 birds each, according to the following experimental design: a control group fed a basal diet (T1), and four groups with dietary replacement of SBM by 25% BSFL (T2), 50% BSFL (T3), 75% BSFL (T4), and 100% BSFL (T5). All groups were maintained under identical management and environmental conditions. At the end of the 35-day experimental period, the broilers were slaughtered, dressed, and weighed. The results showed that the 25% substitution level (T2) gave the best results, significantly improving body weight, weight gain, and the feed conversion ratio (FCR) with normal feed intake. The 50% group (T3) maintained a stable carcass weight similar to the control but showed lower feed intake. In contrast, higher levels (75% and 100%) decreased growth performance and carcass quality due to the high chitin content in the insect exoskeleton. Blood profiles and liver enzymes (ALT and AST) remained normal in most groups, confirming that the diet was safe. However, the 100% group (T5) showed higher cholesterol and HDL levels, and a lower albumin-to-globulin (A/G) ratio. Tissue analysis revealed only mild, non-pathogenic immune responses in the liver and lymphoid organs. Furthermore, BSFL did not alter the cecal microbial balance, maintaining normal Lactobacillus spp. and coliform counts, and all groups remained Salmonella-free. In conclusion, these findings indicate that BSFL can safely replace up to 50% of dietary SBM without compromising broiler health, development, or physiological status. This establishes BSFL as a viable, sustainable alternative protein source capable of reducing reliance on traditional soybean meal in poultry production, provided inclusion rates are optimized to prevent nutritional imbalances at higher substitution levels.
Developing oral radioprotectants for radiation-induced gastrointestinal syndrome (RIGS) is hindered by the non-renewable catalytic capacity of conventional antioxidants and the harsh gastrointestinal biological barriers. Herein, we developed a self-regenerating bio-hybrid nanozyme, SW@CeO2, by in situ growth of cerium oxide on electroactive Shewanella oneidensis (SW). Uniquely, this system exploits bacterial extracellular electron transfer (EET) to continuously fuel the reversible Ce3+/Ce4+ redox cycle, thereby sustaining the catalytic scavenging of radiation-induced reactive oxygen species (ROS). Following oral administration, SW@CeO2 demonstrates exceptional gastrointestinal stability, favorable biodistribution, and efficient intestinal colonization. In a lethal irradiation mouse model, the bio-hybrid effectively mitigates oxidative stress, preserves intestinal barrier integrity, and reshapes the gut microbiota by enriching beneficial taxa such as Lactobacillaceae. Remarkably, SW@CeO2 increases the survival rate from 0% to 80%. This study presents a novel paradigm of harnessing microbial electron transport to sustain inorganic nanozyme activity, providing a robust and translatable solution for radioprotection.
Nanoparticles originating from plants have attracted increasing attention owing to the excellent biocompatibility and high potential in disease prevention. Various types of plant-derived nanoparticles have been extensively studied; however, comparative investigations of different nanoparticles originating from the same plant remain limited. In this study, two types of Pueraria lobata-derived nanoparticles-extracellular vesicle-like nanoparticles (PLEVs) and decoction nanoparticles (DE-NPs)-were isolated, and their physicochemical properties and therapeutic activities were systematically compared. PLEVs exhibited superior resistance to digestion and showed extensive distribution to the liver, demonstrating an enhanced ability to overcome the intestinal barrier and reach the liver. In a mouse model of alcoholic liver disease (ALD), PLEVs were internalized by hepatic macrophages, promoting their polarization into anti-inflammatory M2 and scavenging intracellular reactive oxygen species. Although DE-NPs were digested by enzymes in the gastrointestinal tract, they also possessed beneficial effects by maintaining the intestinal barrier integrity and modulating gut microbiota balance. Overall, PLEVs exhibited a superior hepatoprotective effect, which was associated with the restoration of intestinal homeostasis and the attenuation of hepatic inflammation. These findings highlight the distinct delivery pathways and therapeutic mechanisms of the two Pueraria lobata-derived nanoparticles, addressing PLEVs as a promising natural nanomedicine for alleviating liver-related diseases.
Human noroviruses (HuNoV) are the most common cause of viral gastroenteritis worldwide, causing sporadic cases and outbreaks. Noroviruses that infect wild and domestic animals, including pigs and dogs, are genetically related to human noroviruses, increasing the potential for cross-species transmission. To investigate the potential of noroviruses to cross the species barrier, we used porcine, canine, and avian precision-cut intestinal slices. We show that human norovirus virus-like particles (VLPs) bind to pig and dog intestinal tissue and are taken up with a similar efficiency as the porcine and canine noroviruses, respectively. In contrast, no binding or internalization of human, porcine, or canine noroviruses was detected in chicken tissue. We further showed that human norovirus replicates in pig intestinal tissue. In contrast, while animal noroviruses attached to human intestinal cells, intracellular uptake was limited. This suggests that human-to-animal transmission is more likely than animal-to-human transmission and that viral uptake likely presents a species barrier.