Intestinal Oxidative Stress Research Articles

Intestinal stearoyl-coenzyme A desaturase-inhibition improves obesity-associated metabolic disorders

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Structural characterization of the polysaccharides from Atractylodes chinensis (DC.) Koidz. and the protective effection against alcohol-induced intestinal injury in rats

A neutral polysaccharide, AP, with a weight-average molecular weight of 60.61 kDa, consisting mainly of arabinose and galactose, was isolated from the rhizomes of Atractylodes chinensis (DC.) Koidz. Methylation analyses and nuclear magnetic resonance spectroscopy indicated that the probable repeat unit of AP was →3,6)-α-D-Galp-(1→ residues and constituted the main chain, with a side chain of →5)-α-L-Araf-(1→ and terminal α-L-Araf attached to C-6 of the main chain. The protective activity and potential mechanisms of action of AP on the intestinal tract were investigated. AP improved intestinal oxidative stress injury and inflammatory responses by promoting the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and inhibiting the toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-kappa B signaling pathway, but also repaired colonic mucosal injury and reduced intestinal leakage of endotoxins by promoting expression of the tight-junction proteins zonula occludens-1 and occludin. AP improved ecological dysregulation of the intestinal microbiota and promoted the growth of the potentially beneficial bacteria Lactobacillus_taiwanensis, Limosilactobacillus_reuteri and Akkermansia_muciniphila. AP promoted intestinal health by increasing the production of potentially beneficial metabolites such as short-chain fatty acids, Indole-3-propionic acid, and N-Eicosapentaenoyl tryptophan through metabolism (amino acids, lipids, carbohydrates). These results suggest that AP is a promising prebiotic in attenuating alcohol-induced intestinal damage.

Anti-Inflammatory Effects of Novel Probiotic Lactobacillus rhamnosus RL-H3-005 and Pedicoccus acidilactici RP-H3-006: In Vivo and In Vitro Evidence.

Probiotics have garnered escalating attention in the treatment and prevention of inflammatory disorders. In this study, Lactobacillus rhamnosus RL-H3-005 (RL5) and Pediococcus acidilactici RP-H3-006 (RP6), which possess anti-inflammatory effects and favorable probiotic attributes, were selected through the comparison of an RAW264.7 inflammatory cell model screening and in vitro probiotic properties. Subsequently, it was implemented in an animal model of dextran sulfate sodium (DSS)-induced colitis. The results demonstrated that RL5 and RP6 could inhibit the release of proinflammatory factors in RAW264.7 inflammatory cells and exhibited excellent environmental adaptability, adhesion, safety, and antibacterial activity. Additionally, RL5 and RP6 provided protective effects on the intestines of mice with acute colitis by reducing the levels of intestinal inflammation and oxidative stress. Concurrently, supplementation with RL5 and RP6 modulated the composition of the gut microbiota in mice. These discoveries suggest that RL5 and RP6 can be used as a novel probiotic for alleviating intestinal inflammation.

Protective role of short-chain fatty acids on intestinal oxidative stress induced by TNF-α.

Inflammatory bowel diseases (IBD) are driven by an exaggerated inflammatory response, which leads to a marked increase in oxidative stress. This, in turn, exacerbates the inflammatory process and causes significant cellular and tissue damage. Intestinal dysbiosis, a common observation in IBD patients, alters the production of bacterial metabolites, including short-chain fatty acids (SCFAs), which are key by-products of dietary fiber fermentation. While the role of SCFAs in intestinal physiology is still being elucidated, this study aimed to investigate their effects on intestinal oxidative stress, particularly under inflammatory conditions induced by the proinflammatory mediator tumour necrosis factor alpha (TNF-α). The Caco-2/TC7 cell line was employed as an in vitro model of the intestinal epithelium, and the cells were treated with a range of SCFAs, including acetate, propionate, and butyrate. The levels of protein and lipid oxidation were quantified, as well as the activity of antioxidant enzymes. Our findings demonstrate that microbiota-derived SCFAs can effectively mitigate TNF-α-induced oxidative stress by modulating antioxidant enzyme activity. The proinflammatory mediator TNF-α induces lipid peroxidation by inhibiting catalase and glutathione peroxidase activities. SCFAs are able to upregulate antioxidant enzyme activity to restore lipid oxidative levels. These results underscore the critical role of the gut microbiota in maintaining intestinal homeostasis and highlight the therapeutic potential of SCFAs in managing oxidative stress-related pathologies.

Oxidative Stress in Poultry and the Therapeutic Role of Herbal Medicine in Intestinal Health.

The intensive broiler farming model has accelerated the development of the poultry farming industry. However, it has also inevitably brought about many stressors that lead to oxidative stress in the organism. The intestine is the leading site of nutrient digestion, absorption, and metabolism, as well as a secretory and immune organ. Oxidative stress in animal production can harm the intestine, potentially leading to significant losses for the farming industry. Under conditions of oxidative stress, many free radicals are produced in the animal's body, attacking the intestinal mucosal tissues and destroying the barrier integrity of the intestinal tract, leading to disease. Recently, herbs have been shown to have a favorable safety profile and promising application in improving intestinal oxidative stress in poultry. Therefore, future in-depth studies on the specific mechanisms of herbs and their extracts for treating intestinal oxidative stress can provide a theoretical basis for the clinical application of herbs and new therapeutic options for intestinal oxidative stress injury during poultry farming. This review focuses on the causes and hazards of oxidative stress in the intestinal tract of poultry, and on herbs and their extracts with therapeutic potential, to provide a reference for developing and applying new antioxidants.

Utilizing the apical-out enteroids in vitro model to investigate intestinal glucose transport, barrier function, oxidative stress, and inflammatory responses in broiler chickens.

Conventional 2D intestinal epithelial cell lines have been widely used in investigating intestinal functions, yet with limitations in recapitulating the in vivo gut physiology of chickens. A recently established chicken enteroid model with apical-out nature and the presence of leukocyte components represents intestinal mucosal functions. The objectives of this study were to 1) evaluate basic gut nutrient transport and barrier functions in this model and 2) identify the model's effectiveness in studying inflammation and oxidative stress responses. Enteroids were generated from individual villus units isolated from the small intestine of Cobb500 broiler embryos. Enteroid viability, morphology, and epithelial cell markers were monitored; barrier function was evaluated based on the permeability to fluorescein isothiocyanate-dextran (FD4) with or without EDTA and lipopolysaccharide (LPS) challenges; nutrient transport was evaluated by fluorescence-labeled glucose (2NBD-G) with or without transporter blockade; the oxidative status was indicated by reactive oxygen species (ROS). Inflammatory and oxidative challenges were induced by LPS and menadione treatment, respectively. Selected marker gene expressions, including tight junction proteins (CLDN-1, CLDN-2, ZO-1, and OCCL), epithelial cell markers (Lgr-5, LYZ, and MUC-2), cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, and INF-γ), and antioxidant enzymes (Nrf-2, catalase, and SOD), were determined by using RT-qPCR. Data were analyzed by one-way ANOVA among treatment groups. Enteroid cell activity was stable from day (d) 2 to d 6 and declined at d 7. Epithelial cell marker and cytokine expressions were stable from d 4 to d 6. FD4 permeability was increased after the EDTA treatment (P ≤ 0.05). Transporter-mediated 2NBD-G absorption was observed, which was reduced with glucose transporter blockade (P ≤ 0.05). Enteroids showed classic responses to LPS challenges, including upregulated gene expressions of IL-1β and IL-6, downregulated gene expressions of ZO-1 and OCCL, and increased FD4 permeability (P ≤ 0.05). Enteroids showed increased ROS generation (P ≤ 0.05) in response to oxidative stress. In conclusion, this apical-out enteroid model is a stable alternative in vitro model that exhibits intestinal barrier, nutrient transport, oxidation, and inflammation functions. With this enteroid model, we developed two challenge protocols for evaluating intestinal functions under oxidative stress and inflammation conditions.

Microbiome-based therapies for Parkinson's disease.

The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.

Colon-targeted self-assembled nanoparticles loaded with berberine double salt ameliorate ulcerative colitis by improving intestinal mucosal barrier and gut microbiota

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease marked by disturbances in intestinal mucosal barriers, persistent inflammation, oxidative stress, and dysbiosis of the intestinal microbiota. Traditional treatments often fail to adequately address these issues, primarily targeting inflammation. To address these limitations, this study developed an innovative approach using self-assembled nanoparticles for oral administration that target colonic inflammation. Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. An amphiphilic polymer (FU-PA) was created by esterifying fucoidan with palmitic acid. FU-PA/BeU nanoparticles were prepared using the nanoprecipitation method and further encapsulated in acid-resistant sodium alginate microspheres (FU-PA/BeU NPs@MS) for targeted delivery to colonic lesions. The aggregation rate of nanoparticles with mucus was significantly reduced to 59 % of free berberine, while the apparent permeability coefficient increased by 2.4 times. In vitro, FU-PA/BeU NPs effectively targeted inflammatory macrophages, reducing IL-6 and NO levels while increasing IL-10 level (to 42.5 %, 26.8 %, and 539 % of the LPS-treated group, respectively). Additionally, the ABTS and DPPH radical scavenging capabilities of FU-PA/BeU NPs were 177.8 % and 151.7 % of BeU, respectively. In dextran sulphate sodium-induced UC mice, oral FU-PA/BeU NPs@MS significantly improved epithelial and mucosal barriers, restored gut microbiota diversity, reduced inflammation and oxidative stress. Remarkably, the mean colon length in the FU-PA/BeU NPs@MS group was 1.2 times longer than that in the sulfasalazine group. These dual-targeted FU-PA/BeU NPs@MS show great potential for UC treatment.

Fucoidan from Stichopus chloronotus relieved DSS induced ulcerative colitis through inhibiting intestinal barrier disruption and oxidative stress.

Intestinal barrier disruption and oxidative stress are the major pathological features during the ulcerative colitis (UC). The present research aimed to explore the amelioration property of fucoidan of Stichopus chloronotus (FucSc) against dextran sulfate sodium (DSS) resulted UC. The findings from our study suggest that treating with Fuc-Sc improved the integrity of the Caco-2 monolayer through raising its TEER value, reducing LDH release, promoting the tight junction proteins (TJs) in Caco-2 cells, and shielding the cells from decreases of these proteins caused by H2O2. Besides, Fuc-Sc activated Nrf2/HO-1 pathway to facilitate the antioxidant activities of Caco-2 cells under oxidative stress through elevating the SOD and GSH, and reducing LDH and MDA. Furthermore, oral administration of Fuc-Sc attenuated DSS resulted body weights decrease, DAI score increase, colon length decrease, and structural damage of colon tissue. Fuc-Sc also promoted the barrier function and suppressed oxidative injury via activation of Nrf2/HO-1 signal path. Collectively, this research provided the theoretical foundation for fucoidan as a promising functional food for colitis.

Mechanisms underlying mitochondrial dysfunction and intestinal damage induced by ingestion of microplastics in Leuciscus waleckii: The role of the NF-κB/Nrf2 signaling pathway

This study investigates the impact of polystyrene microplastics (PS-MPs) on the growth, immunity, oxidative stress, mitochondrial function, and intestinal health of Leuciscus waleckii (3.00±0.02 g) juveniles over 8 weeks. Our findings indicate that exposure to PS-MPs negatively affected the growth of Leuciscus waleckii, resulting in digestive disturbances. Furthermore, PS-MPs triggered immune dysfunction and oxidative stress through the activation of the NF-κB pathway and suppression of the Nrf2 signaling cascade. PS-MPs damaged intestinal tissue and compromised the intestinal barrier. Additionally, mitochondrial homeostasis was disrupted, activating endogenous mitochondrial apoptotic pathways, ultimately leading to cell apoptosis. High-throughput 16S rRNA sequencing disclosed that PS-MPs provoked shifts in the intestinal microbiota. Mantel analysis indicates significant correlations between growth parameters and the activities of enzymes related to antioxidant defense, immunity, apoptosis, and mitochondria, as well as with the gut microbiota. In summary, our study reveals that PS-MPs induce intestinal inflammation and oxidative stress in Leuciscus waleckii by activating the NF-κB pathway and the intrinsic mitochondrial apoptotic pathway while repressing the Nrf2 signaling, ultimately leading to cellular apoptosis, mitochondrial dysfunction, intestinal microbiota imbalance, and growth inhibition.

Gastrointestinal fate of proteins from commercial plant-based meat analogs: Silent passage through the stomach, oxidative stress in intestine, and gut dysbiosis in Wistar rats.

Plant-based meat analogs (PBMAs) are common ultra-processed foods (UPFs) included in the vegan/vegetarian diets as presumed healthy alternatives to meat and meat products. However, such health claims need to be supported by scientific evidence. To gain further insight into this topic, two commercial UPFs typically sold as meat analogs, namely, seitan (S) and tofu (T), were included in a cereal-based chow and provided to Wistar rats for 10weeks. A group of animals had, simultaneously, an isocaloric and isoprotein experimental diet formulated with cooked beef (B). In all cases, experimental chows (∼4kcal/g feed) had their basal protein concentration increased from 14% to 30% using proteins from S, T, or B. Upon slaughter, in vivo protein digestibility was assessed, and the entire gastrointestinal tract (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Metagenomics was also applied to assess the variation of microbiota composition as affected by dietary protein. Diets based on PBMAs showed lower protein digestibility than those containing meat and promoted an intense luminal glycoxidative stress and an inflammatory intestinal response. The fermentation of undigested oxidized proteins from T in the colon of Wistar rats likely led to formation of mutagenic metabolites such as p-cresol. The presence of these compounds in the animal models raises concerns about the potential effects of full replacement of meat by certain PBMAs in the diet. Therefore, future research might target on translational human studies to shed light on these findings.

Ganjiang Huangqin Huanglian Renshen Decoction protects against ulcerative colitis by modulating inflammation, oxidative stress, and gut microbiota

BackgroundUlcerative colitis (UC) is a disease that is difficult to treat and has been associated with high rates of recurrence. Moreover, the current medications for UC induce serious side effects following prolonged use. Ganjiang Huangqin Huanglian Renshen Decoction (GJHQHLRSD), has been traditionally used to treat UC. However, its protective mechanisms have not been fully studied. PurposeIn this study the mechanisms by which GJHQHLRSD treats UC was investigated. MethodsThe GJHQHLRSD and GJHQHLRSD drug-containing serum (GJHQHLRSD-DS) were characterized using LC-MS/MS. The therapeutic effect of GJHQHLRSD on dextran sodium sulfate (DSS)-induced UC was explored by assessing various parameters including intestinal flora 16S rRNA, intestinal barrier function, oxidative stress (OS) response, inflammatory cytokines, colonic histopathological injury, colon length, disease activity index (DAI) and body weight. ResultsTreatment with GJHQHLRSD increased body weight, ameliorated colon length shortening and edema, reduced the DAI score, improved the pathological injury, down-regulated the levels of IL-1β, IL-6, IL-8, TNF-α, LPS, LDH, TLR4, and NLRP3, and up-regulated the ZO-1 and Occludin levels in UC mice. It also decreased intestinal oxidative stress in UC mice and improved mitogenic activity by modulating mitochondrial ultrastructure as well as the expression level of PINK1, LC3-II/Ⅰ, Beclin-1, p62, and Parkin proteins. In addition, we found that the effects of GJHQHLRSD on UC mice were inhibited by 3-MA.GJHQHLRSD treatment reduced the imbalance of intestinal flora in UC mice, by regulating the inflammation and oxidative stress. ConclusionThese findings suggested that GJHQHLRSD effectively attenuated inflammatory responses, inhibited the TLR4/NF-κB/NLRP3 signalling, oxidative stress, and modulated the gut microbiota, and alleviated the DSS-induced UC symptoms, making it a promising and innovative therapeutic option for the treatment of UC.

A multiple biomarker approach to understand the effects of microplastics on the health status of European seabass farmed in earthen ponds on the NE Atlantic coast

The occurrence of microplastics (MPs) in aquaculture environments is a growing concern due to their potential negative effects on fish health and, ultimately, on seafood safety. Earthen pond aquaculture, a prevalent aquaculture system worldwide, is typically located in coastal and estuarine areas thus vulnerable to MP contamination. The present study investigated the possible relation between MP levels of European seabass (Dicentrarchus labrax) farmed in an earthen pond and its health status. More precisely, two groups of fish were established based on the lowest and highest number of MPs found collectively in their gastrointestinal tract (GIT), liver, and dorsal muscle: fish with ≤2 MP/g and fish with ≥4 MP/g. The intestinal integrity and oxidative stress biomarkers in the liver and dorsal muscle were evaluated in the established groups. No significant differences in the biometric and organosomatic parameters between groups were observed. The results indicated a significant increase in the number of acid goblet cells (GC) in the rectum of fish with higher MP levels (p = 0.016). Increased acid GC number may constitute a first defence strategy against foreign particles to protect the intestinal epithelium. No significant differences in oxidative stress biomarkers between the two fish groups were observed, namely in the activity of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase in the liver, or in lipid peroxidation levels in the liver and dorsal muscle. The overall results suggest that MP levels were possibly related to an intestinal response but its potential implications on the health status of pond-farmed seabass warrant further investigation. Monitoring MP occurrence across stages of aquaculture production could help to elucidate the potential threats of MPs to fish health.

Physiology, gene expression, and behavior as potential indicators of oxidative stress in piglets

The goal of the current study was to develop a pig model to investigate oxidative stress with a low negative impact on piglet welfare. Four independent trials (A, B, C, and D) were performed using a single intraperitoneal shot of lipopolysaccharide (LPS) as an immune challenge, aiming to assess the minimal LPS dose for piglets of different age to trigger a measurable acute oxidative stress response in healthy animals. In trial A, piglets received an LPS dose of 25 µg/KgBW at 41 days post-weaning (p.w.). In trial B, piglets received 25 µg/KgBW of LPS at 28 days p.w., in trials C And D, piglets were injected with 50 µg/KgBW of LPS at 21 days p.w., respectively. Piglets were randomly allocated either to the T1) Control group with saline solution (Ctrl), or T2) LPS challenge (LPS). The oxidative stress response was measured through the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT), in both plasma and intestinal tissues. Intestinal gene expression of oxidative stress and inflammatory markers was assessed. Discomfort behaviors (panting, prostration, trembling, and vomits) were also recorded. Plasmatic and intestinal oxidative stress response was inconsistent across the four trials even when the dose and pig age were similar, possibly due to individual variability. Relative gene expression differences of anti-inflammatory cytokines (IL10), oxidation precursor (iNOS), and antioxidant markers (GPx4, MnSOD, and CAT) were detected between Ctrl and LPS treatment (P < 0.05) when assessed. Behavioral observations were sensitive to the LPS dose relative to Ctrl (P < 0.05) in all four trials. These results suggest that behavioral observations can be used as a non-invasive methodology to detect the presence of oxidative stress in pigs in challenging conditions. Behavioral observations were more sensitive than other indicators (i.e., biomarkers and gene expression) in the current study. However, a sensitivity scale system needs to be developed to qualify and rank the impact of oxidative stress in pigs.

Impact of Lyophilized Milk Kefir-Based Self-Nanoemulsifying System on Cognitive Enhancement via the Microbiota-Gut-Brain Axis.

Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut-brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut-brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels.

Whole-transcriptome analysis reveals the effect of retinoic acid on small intestinal mucosal injury in cage-stressed young laying ducks

Retinoic acid (RA) is an active derivative of vitamin A and is involved in a variety of physiological processes, including cell growth, antioxidant, and inflammation. However, the role of RA in intestinal oxidative stress injury in caged-stressed laying ducks is unknown. In this study, we analyzed the effect and underlying mechanism of RA supplementation on intestinal damage in cage-stressed young laying ducks. One hundred and sixty laying ducks were divided into 5 treatment groups, including a control group (CR) and 4 treatment groups exposed to different RA concentrations (2,500, 5,000, 7,500 and 10,000 IU/kg, TG1 to TG4). The experimental period comprised a 7-d prefeeding period and a 10-d experimental feeding period, for a total of 17 d. Phenotypic analysis revealed that compared with the control group, RA addition increased the intestinal villus height and the villus-to-crypt ratio; decreased the crypt depth (P < 0.01); decreased the serum diamine oxidase and D-lactate concentrations (P < 0.05); increased the serum antioxidant capacity and intestinal antioxidant gene expression levels (P < 0.05); and increased the expression levels of tight junction-related genes, with the greatest effect observed in TG2 group. Our further whole-transcriptome analysis of duodenum tissues from CR and TG2 ducks revealed 706 differentially expressed mRNAs (DEmRNAs), 357 differentially expressed lncRNAs (DElncRNAs), 14 differentially expressed circRNAs (DEcircRNAs), and 4 differentially expressed miRNAs (DEmiRNAs). These DEGs are involved in calcium signaling, NOD-like receptor signaling, pyruvate metabolism, Jak-STAT signaling, Wnt signaling, riboflavin metabolism, and the adherens junction and tight junction pathways. The results of omics and marker gene expression analysis suggested that RA treatment may play a role in endoplasmic reticulum stress (ERS) and apoptosis. In conclusion, the addition of RA to the diet improved intestinal injury by improving the redox homeostasis of intestinal cells associated with ERS, enhancing the intestinal tight junction structure and alleviating the apoptosis of intestinal epithelial cells; moreover, 5,000 IU/kg RA was determined to be the most appropriate concentration for supplementation.

The Effect of In Vitro Digestion on the Anti-allergic, Anti-Inflammatory and Antioxidant Properties of Purple Rice and Purple Barley Phenolic Extracts in Caco-2 and RBL-2H3 Cells

Gastrointestinal diseases are associated with increased oxidative stress and inflammation. Pigmented cereal polyphenols are believed to have therapeutic potential. However, the impact of digestion on their bioactivity has not been fully elucidated. This study investigated the impact of digestion on the ability of purple rice extract (PRx) and purple barley (PBx) to alleviate oxidative stress-induced intestinal epithelial cell death and allergic inflammation. The study used a human colon adenocarcinoma (Caco-2) cell line to simulate intestinal oxidative stress for 4 h using 1 mM hydrogen peroxide. To evaluate the protective effects of digested and undigested cereal extracts, cells were first pre-treated with varying concentrations (50, 100, 200, and 500 μg/ml) of both purple rice (PRx) and purple barley (PBx) extracts. A rat basophilic leukemia (RBL-2H3) cell line was used to investigate the ability of the extracts to prevent calcium ionophore-induced histamine and cytokine release. The results demonstrated that both digested and undigested phenolic extracts prevented oxidative stress-induced cell death in Caco-2 cells and reduced Interleukin (IL)-8 secretion. PRx showed greater cytoprotective effects than PBx. Both digested and undigested extracts showed a time-dependent antihistamine effect, with the greatest inhibitory effects observed after 2 h and 4 h of treatment with PRx. Additionally, the extracts significantly attenuated the release of several cytokines including IL-2, IL-4, IL-13, monocyte chemoattractant protein-1, interferon-gamma, and tumour necrosis factor-alpha. Overall, the study demonstrates that both digested and undigested pigmented rice and barley extracts are potential sources of polyphenols which may promote intestinal health and alleviate allergic inflammation.

Dietary Clostridium butyricum metabolites mitigated the disturbances in growth, immune response and gut health status of Ctenopharyngodon idella subjected to high cottonseed and rapeseed meal diet

Cottonseed meal and rapeseed meal exhibit a potential for fishmeal substitute in grass carp feed, while their excessive use contribute to growth decline and weakening immunity of aquatic animals. Clostridium butyricum metabolites (CBM) was recognized as a functional additive due to its antioxidant properties and maintenance of intestinal microbiota balance. CBM was added to a high of cottonseed and rapeseed meal diet to determine its effects on growth, immunity, and intestinal microbiota alterations of grass carp (Ctenopharyngodon idella) over 56 days. Eight hundred grass carp (mean weight, around 50 g) were randomized to five treatments and fed with the basic diet (CON), CBM0 diet (28 % cottonseed and 27 % rapeseed meal), and CBM diets (CBM0.5, CBM1, and CBM2, namely CBM0 diet supplemented with 500, 1000, and 2000 mg kg−1 CBM). The results indicated that compared to CBM0, The ingestion of 1000 mg kg−1 CBM diet by grass carp significantly promoted growth as measured by intestinal lipase activity, villus height, and muscle thickness. Moreover, accompanied by a decrease in intestine MDA content, and enhance antioxidant capacity by activating Keap1/Nrf2 signaling pathway to increase enzyme activities (SOD, CAT and T-AOC) and corresponding gene expression (mnsod, cat, gsto and gpx1) in the intestine of grass crap fed CBM1 diet. The dietary CBM1 diet increased serum levels of C3 and IgM, increased ACP activity and expression of the corresponding anti-inflammatory factors (tgf-β1 and il-15), and suppressed the expression of pro-inflammatory factors (tnf-α and il-12β), resulting in enhanced immunity. The dietary CBM1 diet up-regulates gene expression of tight junction proteins (zo-1, occludin, occludin7a and occludin-c), coupled with the decreases in DAO and D-lactate contents, implying that the decreased mucosal permeability could be observed in the gut. The dietary CBM1 diet largely altered the intestinal microbial community, especially reducing the relative abundance of intestinal pathogenic bacteria (Streptococcus and Actinomyces). And it significantly increased the content of short-chain fatty acids (acetic acid, butyric acid, isobutyric acid, propionic acid and isovaleric acid). Taken above, dietary CBM supplementation improved growth in grass carp and attenuated the intestinal oxidative stress, inflammation and microflora dysbacteriosis caused by high proportions of cottonseed and rapeseed meal diets.

Biomineralized ZIF-8 Encapsulating SOD from Hydrogenobacter Thermophilus: Maintaining Activity in the Intestine and Alleviating Intestinal Oxidative Stress.

Oxidative stress is a major factor leading to inflammation and disease occurrence, and superoxide dismutase (SOD) is a crucial antioxidative metalloenzyme capable of alleviating oxidative stress. In this study, a novel thermostable SOD gene is obtained from the Hydrogenobacter thermophilus strain (HtSOD), transformed and efficiently expressed in Escherichia coli with an activity of 3438 Umg-1, exhibiting excellent thermal stability suitable for scalable production. However, the activity of HtSOD is reduced to less than 10% under the acidic environment. To address the acid resistance and gastrointestinal stability issues, a biomimetic mineralization approach is employed to encapsulate HtSOD within the ZIF-8 (HtSOD@ZIF-8). Gastrointestinal simulation results show that HtSOD@ZIF-8 maintained 70% activity in simulated gastric fluid for 2h, subsequently recovering to 97% activity in simulated intestinal fluid. Cell and in vivo experiments indicated that HtSOD@ZIF-8 exhibited no cytotoxicity and do not impair growth performance. Furthermore, HtSOD@ZIF-8 increased the relative abundance of beneficial microbiota such as Dubosiella and Alistipes, mitigated oxonic stress and intestinal injury by reducing mitochondrial and total reactive oxygen species (ROS) levels in diquat-induced. Together, HtSOD@ZIF-8 maintains and elucidates activity in the intestine and biocompatibility, providing insights into alleviating oxidative stress in hosts and paving the way for scalable production.

Effects of cardamonin on the growth performance, intestinal barrier function and intestinal microbiota of Danzhou chickens under heat stress

The aim of this study was to investigate the effects of cardamonin (CDN) on the growth performance, intestinal mucosal barrier function and intestinal microbiota of Danzhou chickens under heat stress. A total of 200 one-day-old female Danzhou chickens were randomly divided into 5 groups. The daytime temperature of heat stress (HS) was set at 36 ± 2°C, and the nighttime temperature was kept the same as in the control (CON) group at 25 ± 2°C. The formal experiment lasted for 21 d. The CON and HS groups were fed a basal diet, whereas the L-CDN, M-CDN, and H-CDN groups received a basal diet supplemented with 50, 100, and 200 mg/kg CDN, respectively. Compared with the HS group, the CDN group presented a significantly greater average daily gain (ADG) (P < 0.001) but a significantly lower feed-to-gain ratio (F/G) (P = 0.007). CDN supplementation also increased the villus height (VH) and the ratio of the villus height to crypt depth (V/C) (P < 0.001) and reduced intestinal permeability by increasing expression of the ZO-1 (P < 0.001), Occludin (P < 0.001), and Claudin-1 (P = 0.034) proteins and decreasing the content of D-lactic acid (D-LA) and the activity of diamine oxidase (DAO) in serum (P < 0.001). Additionally, CDN reduced the levels of the intestinal mucosal inflammatory factors (IL-1β (P = 0.031), IL-6 (P = 0.003), and TNF-α (P = 0.014)) while upregulating IL-10 (P < 0.001). Furthermore, it increased the total antioxidant capacity (T-AOC) (P = 0.004) and catalase (CAT) activity (P < 0.001) and reduced the malondialdehyde (MDA) content (P = 0.017), effectively reducing intestinal oxidative stress and inflammatory reactions. Expression of the Nrf2 pathway-related proteins Nrf2 (P = 0.012), HO-1 (P = 0.008), and NQO1 (P = 0.003) was also increased by CDN. Moreover, feeding CDN increased the proportion of beneficial bacteria such as Firmicutes and Bacteroidetes but decreased the proportion of harmful bacteria such as Proteobacteria, thus protecting the intestinal barrier. In summary, 200 mg/kg CDN in the diet improved growth performance, enhanced intestinal barrier function and improved intestinal flora disorders in heat stress-induced Danzhou chickens, which may be related to the Nrf2/NQO1 signaling pathway.