The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to...The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.展开更多
Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weigh...Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weight gain,and significant economic losses.Results In this study,we isolated an E.coli strain,SKLAN202302,from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin.Piglets infected with E.coli exhibited significant reductions in body weight,feed intake,small intestine length,and ileal goblet cell count(P<0.05),along with deteriorated ileal morphology.However,baicalin supplementation resulted in body weights,feed intake,and intestinal morphology similar to those of the control group.Notably,there was a significant increase in the colonization of Lactobacillus species,particularly Lactobacillus_reuteri,Lactobacillus_amylovorus,and Lactobacillus_johnii,compared to the E.coli group(P<0.05).At the metabolic and transcriptional levels,E.coli infection increased inflammatory mediators,including eicosanoids(leukotriene F4,prostaglandin F1a,leukotriene E4,thromboxane B2,prostaglandin G2,and PGH2),monosaccharides,and TCA cycle intermediates(oxoglutaric acid,glutaric acid,adipic acid,citric acid,and isocitric acid)in the ileum.It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway(CTLA4,IFN-ALPHA-8,IL12RB2,TRAV3,TRAV16,FOS,and VEGFA),as well as inflammatory factors.Conversely,baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids[including lyso PC(P-18:1(9Z)/0:0),PC(17:0/0:0),lyso PC(16:1(9Z)/0:0),PC(18:0/0:0),lyso PC(18:0/0:0),PA(10:0/i-16:0),and PA(10:0/8:0)]and amino acids.It also regulated genes within the IL-17 signaling pathway(IL4,CCL17,CXCL10,IFNG,and CXCL2),suggesting a mechanism by which baicalin mitigates E.coli-induced intestinal and microbial disturbances.Subsequent flow cytometry analysis showed that E.coli infection increased the numbers of CD3+and Foxp3+cells,decreased IL-17A+cells,and reduced Th17/Treg ratios.Baicalin supplementation restored these parameters to control levels.Conclusions Baicalin supplementation effectively alleviates E.coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization,counteracting inflammatory mediators,and regulating immune-related gene expression and the Th17/Treg balance.These findings highlight baicalin's potential in alleviating intestinal inflammation.展开更多
The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementati...The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.展开更多
Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation ...Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates,its roles in fish are not well understood.This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis.Results revealed that Pelteobagrus fulvidraco IL-22(Pf_IL-22)was abundantly expressed in mucosal tissues,with the highest levels in the gill and intestine.Hypoxia induced pronounced intestinal injury,characterized by loosening of the lamina propria and extensive vacuolization,while activating hypoxia-inducible factor(HIF)signaling and markedly up-regulating IL-22 expression.IL-22 levels peaked at 24 h post-hypoxia,suggesting a role in early immune responses.Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators,including IL-1βand tumor necrosis factorα(TNF-α),in primary intestinal epithelial cells,indicating a dual regulatory function in balancing protection and inflammation.Mechanistic analyses revealed that HIF-1αdirectly interacted with a hypoxia response element within the IL-22 promoter to drive transcription,as confirmed by dual-luciferase assays,electrophoretic mobility-shift assays,and HIF-1αknockdown.Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways,demonstrating its role in shaping downstream immune responses.These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation,providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.展开更多
AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice ...AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.展开更多
Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasi...Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichuris suis ) have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD.展开更多
Background:High stocking density(HSD)stress has detrimental effects on growth performance,intestinal barrier function,and intestinal microbiota in intensive animal production.Organic acids(OA)are widely used as feed a...Background:High stocking density(HSD)stress has detrimental effects on growth performance,intestinal barrier function,and intestinal microbiota in intensive animal production.Organic acids(OA)are widely used as feed addi-tives for their ability to improve growth performance and intestinal health in poultry.However,whether dietary OA can ameliorate HSD stress-induced impaired intestinal barrier in broilers remains elusive.In this study,a total of 528 one-day-old male Arbor Acres broilers were randomly allocated into 3 treatments with 12 replicates per treatment including 10 birds for normal stocking density and 17 birds for HSD.The dietary treatments were as follows:1)Normal stocking density+basal diet;2)HSD+basal diets;3)HSD+OA.Results:HSD stress can induce increased levels of serum corticosterone,lipopolysaccharides,interleukin-1β,tumor necrosis factor-α,and down-regulated mRNA expression of ZO-1,resulting in compromised growth performance of broilers(P<0.05).Dietary OA could significantly reduce levels of serum corticosterone,lipopolysaccharides,interleukin-1β,and tumor necrosis factor-α,which were accompanied by up-regulated interleukin-10,mRNA expres-sion of ZO-1,and growth performance(P<0.05).Moreover,OA could down-regulate the mRNA expression of TLR4 and MyD88 to inhibit the NF-κB signaling pathway(P<0.05).Additionally,HSD stress significantly decreased the abundance of Bacteroidetes and disturbed the balance of microbial ecosystems,whereas OA significantly increased the abundance of Bacteroidetes and restored the disordered gut microbiota by reducing competitive and exploita-tive interactions in microbial communities(P<0.05).Meanwhile,OA significantly increased the content of acetic and butyric acids,which showed significant correlations with intestinal inflammation indicators(P<0.05).Conclusions:Dietary OA ameliorated intestinal inflammation and growth performance of broilers through restor-ing the disordered gut microbial compositions and interactions induced by HSD and elevating short-chain fatty acid production to inhibit the TLR4/NF-κB signaling pathway.These findings demonstrated the critical role of intestinal microbiota in mediating the HSD-induced inflammatory responses,contributing to exploring nutritional strategies to alleviate HSD-induced stress in animals.展开更多
Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,th...Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.展开更多
AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking f...AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.展开更多
Background:Sarcandra glabra(Thunb.)Nakai,a traditional Chinese herbal medicine,exhibits various biological activities,including antibacterial,anti-inflammatory,and antioxidant properties.However,the biological activit...Background:Sarcandra glabra(Thunb.)Nakai,a traditional Chinese herbal medicine,exhibits various biological activities,including antibacterial,anti-inflammatory,and antioxidant properties.However,the biological activities of its volatile oil components are not well understood.Purpose:This study was aimed to investigate the antibacterial and antioxidant activities of Sarcandra glabra essential oil(SGEO)and explore its potential protective effect on Lipopolysaccharide(LPS)-induced intestinal inflammatory injury in mice.Methods:First,GC-MS was used to identify and quantify the components of SGEO.Its antioxidant activity was assessed by evaluating its free radical scavenging ability.The antibacterial mechanism of SGEO against Methicillin-resistant Staphylococcus aureus(MRSA)was explored by examining changes in MRSA ultrastructure,leakage of cellular contents,ROS levels,and biofilm formation.Next,the protective effects of SGEO(400 and 1200 mg/kg)on intestinal inflammatory damage in mice were evaluated by analyzing physiological parameters,immune and antioxidant responses,jejunal histology,and Tight junction(TJ)protein expression levels.The microbial composition in the cecal contents of mice was analyzed using 16S rDNA sequencing,and the content of short-chain fatty acids was measured by HPLC.Results:SGEO exhibits strong antioxidant activity and inhibits MRSA growth by disrupting the MRSA cell membrane structure,inducing oxidative stress,and inhibiting biofilm formation.Additionally,SGEO alleviates LPS-induced intestinal inflammatory damage in mice by increasing the expression of TJ proteins and regulating the intestinal microecological environment.展开更多
The intestinal barrier plays important roles in the uptake of nutrients and prevention of harmful pathogens.However,intestinal inflammation causes barrier dysfunction,which may contribute to inflammatory bowel disease...The intestinal barrier plays important roles in the uptake of nutrients and prevention of harmful pathogens.However,intestinal inflammation causes barrier dysfunction,which may contribute to inflammatory bowel disease(IBD).Polyphenols from Perilla frutescens(L.)Britt.Exhibit various bioactivities,though their protective effect on the intestinal barrier remains unclear.To address this,the study investigated the effect of Perilla frutescens(L.)Britt.polyphenols(PFP)against tight junction alterations and intestinal inflammation using an intestinal-like Caco-2/macrophage co-culture model.LC-MS/MS analysis identified 15 polyphenols in the PFP extract.Furthermore,PFP were transported across the apical Caco-2 monolayer,with apigenin,genistin,syringic acid and cinnamic acid showing relatively high transport rates(>70%).The lipopolysaccharide(LPS)-induced tight junction alterations,evaluated by trans-epithelial electrical resistance(TEER)analysis,qPCR,and immunofluorescence assay,were significantly restored by medium and high doses of PFP(P<0.05).In addition,network pharmacology analysis demonstrated that the core targets of PFP for intestinal inflammation were mostly located in the MAPK and NF-κB signaling pathways.The expression levels of the key proteins in these pathways were further validated by qPCR and western blot analyses.Overall,PFP exhibits great potential as a novel functional food component for treating intestinal inflammation.展开更多
Ulcerative Colitis(UC),a subtype of inflammatory bowel disease(IBD),is an intestinal inflammatory disease whose pathogenesis is not fully elucidated and difficult to treat.The intervention of L.paracasei JY062 with it...Ulcerative Colitis(UC),a subtype of inflammatory bowel disease(IBD),is an intestinal inflammatory disease whose pathogenesis is not fully elucidated and difficult to treat.The intervention of L.paracasei JY062 with its EPS group(JEC)reduced the apoptosis rate from 30.7%to 14.2%,inhibited myeloperoxidase deficiency(MPO)activity and the level of lipopolysaccharide(LPS).Simultaneously,the results showed that JEC upregulated the transcript levels of transforming growth factor-β(TGF-β)and interleukin 10(IL-10),decreased the mRNA expression of transforming growth factor-α(TNF-α),interferon gamma-γ(IFN-γ),interleukin 6(IL-6),interleukin 17(IL-17),and interleukin-1β(IL-1β).JEC affects cytokines secretion and attenuates the inflammatory response by inhibition of the TLR4/MyD88/NF-κB pathway.TLR4,MyD88,p65 mRNA and protein expression in the JEC group showed significantly reductions,inhibiting IκBαand p65 phosphorylation while effectively inhibiting DSStriggered low expression of IκBα.JEC could modulate intestinal immune homeostasis by increasing the content of acetic acid,propionic acid,isobutyric acid and valeric acid(p<0.05).JEC ameliorates intestinal inflammation,and provide a theoretical basis for the development of hybrid microbial formulations for strategies to alleviate UC.展开更多
Moringa oleifera root polysaccharides(MRP)are important bioactive components of Moringa oleifera and play a key role in mitigating inflammation.In this study,MRP were extracted using a green solvent through an ultraso...Moringa oleifera root polysaccharides(MRP)are important bioactive components of Moringa oleifera and play a key role in mitigating inflammation.In this study,MRP were extracted using a green solvent through an ultrasonic-assisted process,with optimized extraction conditions,and their thermal stability was determined by thermogravimetry(TG)and differential scanning calorimetry(DSC).Five distinct MRP fractions were isolated and purified using DEAE-52 cellulose and Sephadex G-100 gel chromatography,followed by preliminary characterization.To assess the protective effects of MRP on small intestinal inflammation,an LPS-induced mouse model(n=10)was established.The effects of MRP on small intestinal inflammation were then evaluated through H&E staining and ELISA,while the impact on gut microbiota was explored through 16S ribosomal RNA(rRNA)gene sequencing.The results showed that MRP is a heteropolysaccharide containing glucose,mannose,rhamnose,galactose,and arabinose,with glucose as its main component,and it also exhibits excellent thermal stability.MRP intervention alleviated the damage to the small intestinal epithelial tissue and significantly modulated inflammatory responses.Specifically,high-dose MRP reduced serum levels of the pro-inflammatory cytokines,TNF-α,IL-6,and IL-1β,by 32.2%,58.7%,and 38.4%,respectively,compared to the model group(p<0.001),while increasing the level of the anti-inflammatory cytokine IL-10 by 123.6%(p<0.001).Furthermore,16S rRNA gene sequencing revealed that MRP regulated gut microbiota composition by reducing harmful genera(Ruminococcus and Escherichia)and increasing beneficial genera(Lactobacillus,Adlercreutzia,and Odoribacter).The analysis of Alpha and Beta diversity further supported the protective role of MRP in maintaining microbial ecological balance.In conclusion,this study offers novel insights into the structural composition of MRP,for the first time,its protective effects against small intestinal inflammation via cytokine regulation and microbiota modulation.These preliminary findings lay a foundation for further mechanistic and applied research.展开更多
Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbi...Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbiome and short-chain fatty acids(SCFAs)following alcohol intoxication and burn injury and to determine whether these changes are associated with intestinal inflammation.Methods 10–12-week-old C57BL/6 male and female mice were subjected to ethanol intoxication and a 12.5%total body surface area scald burn injury.The following day,mice were euthanised and faecal contents from the caecum and small intestine(SI)were harvested for 16S sequencing for microbial analysis and caecum contents underwent high-performance liquid chromatography mass spectroscopy to assess SCFAs.Results The intestinal microbiome of ethanol burn(EB)mice exhibited decreased alpha diversity and distinct beta diversity compared with sham vehicle(SV).EB faeces were marked by increased Proteobacteria and many pathobionts.EB caecum faeces exhibited a significant decrease in butyrate and a downward trend in acetate and total SCFAs.SCFA changes correlated with microbial changes particularly in the SI.Treatment of murine duodenal cell clone-K(MODE-K)cells with faecal slurries led to upregulation of interleukin-6(IL-6)from EB faeces compared with SV faeces which correlated with levels of Enterobacteriaceae.However,supplementation of butyrate reduced faecal slurry-induced MODE-K cells IL-6 release.Conclusion Together,these findings suggest that alcohol and burn injury induce bacterial dysbiosis and a decrease in SCFAs,which together can promote intestinal inflammation and barrier disruption,predisposing to postinjury pathology.展开更多
In a recent paper published in Nature,Oliver and colleagues report that pyloric gland metaplastic cells within the intestinal epithelium arise from crypt-based stem cells in response to chronic inflammatory irritation...In a recent paper published in Nature,Oliver and colleagues report that pyloric gland metaplastic cells within the intestinal epithelium arise from crypt-based stem cells in response to chronic inflammatory irritation.These metaplastic cells to which the authors refer to as INFLAREs exhibit unique transcriptional signatures and promote inflammation-mediated tissue remodeling.展开更多
Germinal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments.However,the function of hypoxia-inducible factor(HIF)-1αin immunoglobulin production remains inco...Germinal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments.However,the function of hypoxia-inducible factor(HIF)-1αin immunoglobulin production remains incompletely characterized.Here,we demonstrated that B cells lacking HIF-1αexhibited significantly lower glycolytic metabolism and impaired IgA production.Loss of HIF-1αin B cells affects IgA-producing B-cell differentiation and exacerbates dextran sodium sulfate(DSS)-induced colitis.Conversely,promoting HIF-1αstabilization via a PHD inhibitor roxadustat enhances IgA class switching and alleviates intestinal inflammation.Mechanistically,HIF-1αfacilitates IgA class switching through acetyl-coenzyme A(acetyl-CoA)accumulation,which is essential for histone H3K27 acetylation at the Sαregion.Consequently,supplementation with acetyl-CoA improved defective IgA production in Hif1a-deficient B cells and limited experimental colitis.Collectively,these findings highlight the critical importance of HIF-1αin IgA class switching and the potential for targeting the HIF-1α-dependent metabolic‒epigenetic axis to treat inflammatory bowel diseases and other inflammatory disorders.展开更多
Background:Qiwenghuangbo powder(QP),composed of Astragalus,Phellodendron chinensis,and Radix pulsatilla,is a traditional Chinese herbal formula,but its effects on weaned piglets remained unclear.Methods:Weaned piglets...Background:Qiwenghuangbo powder(QP),composed of Astragalus,Phellodendron chinensis,and Radix pulsatilla,is a traditional Chinese herbal formula,but its effects on weaned piglets remained unclear.Methods:Weaned piglets fed with 0.5 kg/t QP(QP1),1 kg/t QP(QP2),low-zinc oxide(ZnO;negative control),and high-ZnO(positive control)diets in two phases,respec-tively,and the growth performance,intestinal morphology,cytokines,and microbial communities were profiled.The mouse models of colitis induced by Citrobacter roden-tium and dextran sulfate sodium(DSS)were employed to elucidate the potential role of QP-fed enriched key species.Results:Dietary 1.0 kg/t QP alleviated diarrhea and inflammation and improved intes-tinal development and growth performance of weaned piglets.Moreover,this dietary intervention notably altered microbiota composition,characterized by the enrich-ment of Limosilactobacillus reuteri.Furthermore,out of three isolated L.reuteri,two strains could alleviate pathogen infection and intestinal inflammation,respectively.Specifically,the anti-inflammatory effect of one strain was achieved by promoting the colonization resistance of C.rodentium as significantly reduced pathogen loads.The other strain mitigated DSS-induced colitis by enhancing the goblet cell function and inhibiting the secretion of pro-inflammatory cytokines,particularly interleukin-1β(IL-1ß)and tumor necrosis factor-α(TNF-α).Conclusions:Dietary QP improved the growth performance and intestinal health of weaned piglets by promoting the colonization of L.reuteri.The isolated commensal L.reuteri control colitis in a strain-specific mechanism,highlighting the potential of QP and L.reuteri in providing evidence for gut health promotion.展开更多
Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates...Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.展开更多
YdjC chitooligosaccharide deacetylase homolog(YDJC)has been identified as a susceptibility gene for inflammatory bowel disease(IBD),yet its role in the pathogenesis of IBD,particularly in regulating immune responses i...YdjC chitooligosaccharide deacetylase homolog(YDJC)has been identified as a susceptibility gene for inflammatory bowel disease(IBD),yet its role in the pathogenesis of IBD,particularly in regulating immune responses in the gut mucosa,remains elusive.In this study,we demonstrated that YDJC expression is downregulated in inflamed mucosa,particularly in the CD4^(+)T cells of IBD patients,and that Ydjc deficiency promotes CD4^(+)T-cell proliferation and Th1 cell differentiation,thereby exacerbating acute and chronic colitis in mice.Integrative transcriptomic,proteomic,and metabolomic analyses revealed that Ydjc^(-/-)CD4^(+)T cells exhibit upregulated SREBP2-mediated cholesterol biosynthesis.Consistently,treatment with key enzyme inhibitors targeting cholesterol biosynthesis,including simvastatin,fatostatin,and AAV-sh-Srebf2,markedly suppressed CD4^(+)T-cell proliferation and Th1 cell differentiation,thereby alleviating colitis in Ydjc^(-/-)mice.Mechanistically,YDJC directly deacetylates SREBP2,which further suppresses downstream target gene expression(e.g.,Hmgcr,Hmgcs1,and Cyp51).Therefore,our findings elucidate a novel mechanism whereby YDJC restrains intestinal mucosal inflammation by downregulating SREBP2-driven Th1 cell differentiation,suggesting that targeting YDJC and SREBP2-mediated cholesterol biosynthesis may serve as promising therapeutic strategies for IBD.展开更多
基金supported by the fund for the Project of the National Key Research and Development Program of China(2024YFD1300203)Project support was provided by the Fund opened from Key Laboratory of Fujian Universities Preventive Veterinary Medicine and Biotechnology,Longyan University(grant No.2021KF01)the Cyanine Project of Yangzhou University(2020)。
文摘The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.
基金supported by the National Natural Science Foundation of China(32102582)the Youth innovation of Chinese Academy of Agricultural Sciences(Y2023QC09)+1 种基金Zhejiang Province Traditional Chinese Medicine Science and technology Project(2022ZB270)the Agricultural Science and Technology Innovation Program(ASTIPIAS07,cxgc-ias-16)。
文摘Background Intestinal inflammation is a common and serious health problem in piglet production,especially enteritis caused by pathogenic Escherichia coli(E.coli).This condition often leads to high mortality,slow weight gain,and significant economic losses.Results In this study,we isolated an E.coli strain,SKLAN202302,from the colon of diarrheal piglets to create an intestinal inflammation model for evaluating the protective effects of baicalin.Piglets infected with E.coli exhibited significant reductions in body weight,feed intake,small intestine length,and ileal goblet cell count(P<0.05),along with deteriorated ileal morphology.However,baicalin supplementation resulted in body weights,feed intake,and intestinal morphology similar to those of the control group.Notably,there was a significant increase in the colonization of Lactobacillus species,particularly Lactobacillus_reuteri,Lactobacillus_amylovorus,and Lactobacillus_johnii,compared to the E.coli group(P<0.05).At the metabolic and transcriptional levels,E.coli infection increased inflammatory mediators,including eicosanoids(leukotriene F4,prostaglandin F1a,leukotriene E4,thromboxane B2,prostaglandin G2,and PGH2),monosaccharides,and TCA cycle intermediates(oxoglutaric acid,glutaric acid,adipic acid,citric acid,and isocitric acid)in the ileum.It also promoted the expression of genes related to autoimmune diseases and the Th17 differentiation signaling pathway(CTLA4,IFN-ALPHA-8,IL12RB2,TRAV3,TRAV16,FOS,and VEGFA),as well as inflammatory factors.Conversely,baicalin supplementation not only counteracted these effects but also enhanced the presence of metabolites such as phospholipids[including lyso PC(P-18:1(9Z)/0:0),PC(17:0/0:0),lyso PC(16:1(9Z)/0:0),PC(18:0/0:0),lyso PC(18:0/0:0),PA(10:0/i-16:0),and PA(10:0/8:0)]and amino acids.It also regulated genes within the IL-17 signaling pathway(IL4,CCL17,CXCL10,IFNG,and CXCL2),suggesting a mechanism by which baicalin mitigates E.coli-induced intestinal and microbial disturbances.Subsequent flow cytometry analysis showed that E.coli infection increased the numbers of CD3+and Foxp3+cells,decreased IL-17A+cells,and reduced Th17/Treg ratios.Baicalin supplementation restored these parameters to control levels.Conclusions Baicalin supplementation effectively alleviates E.coli-induced intestinal inflammation and microbial disturbances in piglets by enhancing beneficial Lactobacillus colonization,counteracting inflammatory mediators,and regulating immune-related gene expression and the Th17/Treg balance.These findings highlight baicalin's potential in alleviating intestinal inflammation.
基金funded by the National Natural Science Foundation of China(32001676)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(CAST)(2022QNRC001).
文摘The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.
基金supported by the National Natural Science Foundation of China(32102760)“JBGS”Project of Seed Industry Revitalization in Jiangsu Province(JBGS(2021)034)+1 种基金Creation Project of Major New Species of Agriculture in Jiangsu Province(PZCZ201742)Key Laboratory of Healthy Freshwater Aquaculture,Ministry of Agriculture and Rural Affairs,Key Laboratory of Freshwater Aquaculture Genetic and Breeding of Zhejiang Province,Zhejiang Institute of Freshwater Fisheries,Huzhou 313001(ZJK202404)。
文摘Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates,its roles in fish are not well understood.This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis.Results revealed that Pelteobagrus fulvidraco IL-22(Pf_IL-22)was abundantly expressed in mucosal tissues,with the highest levels in the gill and intestine.Hypoxia induced pronounced intestinal injury,characterized by loosening of the lamina propria and extensive vacuolization,while activating hypoxia-inducible factor(HIF)signaling and markedly up-regulating IL-22 expression.IL-22 levels peaked at 24 h post-hypoxia,suggesting a role in early immune responses.Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators,including IL-1βand tumor necrosis factorα(TNF-α),in primary intestinal epithelial cells,indicating a dual regulatory function in balancing protection and inflammation.Mechanistic analyses revealed that HIF-1αdirectly interacted with a hypoxia response element within the IL-22 promoter to drive transcription,as confirmed by dual-luciferase assays,electrophoretic mobility-shift assays,and HIF-1αknockdown.Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways,demonstrating its role in shaping downstream immune responses.These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation,providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.
文摘AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.
基金Grant DK 074727 (R21) from the National Institutes of HealthAn unrestricted educational grant from Wyeth NutritionA research fellowship from the Research Center for High Altitude Medicine, Qinghai University Medical School, China
文摘Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichuris suis ) have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD.
基金supported by the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences,and Trouw Nutrition Research&Development Centers.
文摘Background:High stocking density(HSD)stress has detrimental effects on growth performance,intestinal barrier function,and intestinal microbiota in intensive animal production.Organic acids(OA)are widely used as feed addi-tives for their ability to improve growth performance and intestinal health in poultry.However,whether dietary OA can ameliorate HSD stress-induced impaired intestinal barrier in broilers remains elusive.In this study,a total of 528 one-day-old male Arbor Acres broilers were randomly allocated into 3 treatments with 12 replicates per treatment including 10 birds for normal stocking density and 17 birds for HSD.The dietary treatments were as follows:1)Normal stocking density+basal diet;2)HSD+basal diets;3)HSD+OA.Results:HSD stress can induce increased levels of serum corticosterone,lipopolysaccharides,interleukin-1β,tumor necrosis factor-α,and down-regulated mRNA expression of ZO-1,resulting in compromised growth performance of broilers(P<0.05).Dietary OA could significantly reduce levels of serum corticosterone,lipopolysaccharides,interleukin-1β,and tumor necrosis factor-α,which were accompanied by up-regulated interleukin-10,mRNA expres-sion of ZO-1,and growth performance(P<0.05).Moreover,OA could down-regulate the mRNA expression of TLR4 and MyD88 to inhibit the NF-κB signaling pathway(P<0.05).Additionally,HSD stress significantly decreased the abundance of Bacteroidetes and disturbed the balance of microbial ecosystems,whereas OA significantly increased the abundance of Bacteroidetes and restored the disordered gut microbiota by reducing competitive and exploita-tive interactions in microbial communities(P<0.05).Meanwhile,OA significantly increased the content of acetic and butyric acids,which showed significant correlations with intestinal inflammation indicators(P<0.05).Conclusions:Dietary OA ameliorated intestinal inflammation and growth performance of broilers through restor-ing the disordered gut microbial compositions and interactions induced by HSD and elevating short-chain fatty acid production to inhibit the TLR4/NF-κB signaling pathway.These findings demonstrated the critical role of intestinal microbiota in mediating the HSD-induced inflammatory responses,contributing to exploring nutritional strategies to alleviate HSD-induced stress in animals.
基金the financial support provided by“Modern Food Processing,Food Storage,Transportation Technology,and Equipment”State Key Research and Development Plan(2017YFD0400204)the National Science Foundation of China(31972091).
文摘Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.
基金Supported by INBRE P20RR016474USDA-NRI 200835203-19084USDA-AFRI 2009-65203-05716
文摘AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.
基金supported by the Key Research and Development Program of Shaanxi Province(No.2024NC-YBXM-92)the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University(No.CX2024083).
文摘Background:Sarcandra glabra(Thunb.)Nakai,a traditional Chinese herbal medicine,exhibits various biological activities,including antibacterial,anti-inflammatory,and antioxidant properties.However,the biological activities of its volatile oil components are not well understood.Purpose:This study was aimed to investigate the antibacterial and antioxidant activities of Sarcandra glabra essential oil(SGEO)and explore its potential protective effect on Lipopolysaccharide(LPS)-induced intestinal inflammatory injury in mice.Methods:First,GC-MS was used to identify and quantify the components of SGEO.Its antioxidant activity was assessed by evaluating its free radical scavenging ability.The antibacterial mechanism of SGEO against Methicillin-resistant Staphylococcus aureus(MRSA)was explored by examining changes in MRSA ultrastructure,leakage of cellular contents,ROS levels,and biofilm formation.Next,the protective effects of SGEO(400 and 1200 mg/kg)on intestinal inflammatory damage in mice were evaluated by analyzing physiological parameters,immune and antioxidant responses,jejunal histology,and Tight junction(TJ)protein expression levels.The microbial composition in the cecal contents of mice was analyzed using 16S rDNA sequencing,and the content of short-chain fatty acids was measured by HPLC.Results:SGEO exhibits strong antioxidant activity and inhibits MRSA growth by disrupting the MRSA cell membrane structure,inducing oxidative stress,and inhibiting biofilm formation.Additionally,SGEO alleviates LPS-induced intestinal inflammatory damage in mice by increasing the expression of TJ proteins and regulating the intestinal microecological environment.
基金supported by National Natural Science Foundation of China(32402267)Jiangsu Agricultural Science and Technology Innovation Fund,grant number:CX(23)1015+2 种基金Jiangsu Innovative and Entrepreneurial Talents Program,grant number:JSSCBS20230184Nanjing Science and Technology Innovation Project,grant number:3501230357Jiangsu Funding Program for Excellent Postdoctoral Talent,grant number:2024ZB779.
文摘The intestinal barrier plays important roles in the uptake of nutrients and prevention of harmful pathogens.However,intestinal inflammation causes barrier dysfunction,which may contribute to inflammatory bowel disease(IBD).Polyphenols from Perilla frutescens(L.)Britt.Exhibit various bioactivities,though their protective effect on the intestinal barrier remains unclear.To address this,the study investigated the effect of Perilla frutescens(L.)Britt.polyphenols(PFP)against tight junction alterations and intestinal inflammation using an intestinal-like Caco-2/macrophage co-culture model.LC-MS/MS analysis identified 15 polyphenols in the PFP extract.Furthermore,PFP were transported across the apical Caco-2 monolayer,with apigenin,genistin,syringic acid and cinnamic acid showing relatively high transport rates(>70%).The lipopolysaccharide(LPS)-induced tight junction alterations,evaluated by trans-epithelial electrical resistance(TEER)analysis,qPCR,and immunofluorescence assay,were significantly restored by medium and high doses of PFP(P<0.05).In addition,network pharmacology analysis demonstrated that the core targets of PFP for intestinal inflammation were mostly located in the MAPK and NF-κB signaling pathways.The expression levels of the key proteins in these pathways were further validated by qPCR and western blot analyses.Overall,PFP exhibits great potential as a novel functional food component for treating intestinal inflammation.
基金supported by the National Natural Science Foundation of China(No.32172231).
文摘Ulcerative Colitis(UC),a subtype of inflammatory bowel disease(IBD),is an intestinal inflammatory disease whose pathogenesis is not fully elucidated and difficult to treat.The intervention of L.paracasei JY062 with its EPS group(JEC)reduced the apoptosis rate from 30.7%to 14.2%,inhibited myeloperoxidase deficiency(MPO)activity and the level of lipopolysaccharide(LPS).Simultaneously,the results showed that JEC upregulated the transcript levels of transforming growth factor-β(TGF-β)and interleukin 10(IL-10),decreased the mRNA expression of transforming growth factor-α(TNF-α),interferon gamma-γ(IFN-γ),interleukin 6(IL-6),interleukin 17(IL-17),and interleukin-1β(IL-1β).JEC affects cytokines secretion and attenuates the inflammatory response by inhibition of the TLR4/MyD88/NF-κB pathway.TLR4,MyD88,p65 mRNA and protein expression in the JEC group showed significantly reductions,inhibiting IκBαand p65 phosphorylation while effectively inhibiting DSStriggered low expression of IκBα.JEC could modulate intestinal immune homeostasis by increasing the content of acetic acid,propionic acid,isobutyric acid and valeric acid(p<0.05).JEC ameliorates intestinal inflammation,and provide a theoretical basis for the development of hybrid microbial formulations for strategies to alleviate UC.
基金financial support from Scientific Research Project of Education Department of Liaoning Province(JYTMS20231370)。
文摘Moringa oleifera root polysaccharides(MRP)are important bioactive components of Moringa oleifera and play a key role in mitigating inflammation.In this study,MRP were extracted using a green solvent through an ultrasonic-assisted process,with optimized extraction conditions,and their thermal stability was determined by thermogravimetry(TG)and differential scanning calorimetry(DSC).Five distinct MRP fractions were isolated and purified using DEAE-52 cellulose and Sephadex G-100 gel chromatography,followed by preliminary characterization.To assess the protective effects of MRP on small intestinal inflammation,an LPS-induced mouse model(n=10)was established.The effects of MRP on small intestinal inflammation were then evaluated through H&E staining and ELISA,while the impact on gut microbiota was explored through 16S ribosomal RNA(rRNA)gene sequencing.The results showed that MRP is a heteropolysaccharide containing glucose,mannose,rhamnose,galactose,and arabinose,with glucose as its main component,and it also exhibits excellent thermal stability.MRP intervention alleviated the damage to the small intestinal epithelial tissue and significantly modulated inflammatory responses.Specifically,high-dose MRP reduced serum levels of the pro-inflammatory cytokines,TNF-α,IL-6,and IL-1β,by 32.2%,58.7%,and 38.4%,respectively,compared to the model group(p<0.001),while increasing the level of the anti-inflammatory cytokine IL-10 by 123.6%(p<0.001).Furthermore,16S rRNA gene sequencing revealed that MRP regulated gut microbiota composition by reducing harmful genera(Ruminococcus and Escherichia)and increasing beneficial genera(Lactobacillus,Adlercreutzia,and Odoribacter).The analysis of Alpha and Beta diversity further supported the protective role of MRP in maintaining microbial ecological balance.In conclusion,this study offers novel insights into the structural composition of MRP,for the first time,its protective effects against small intestinal inflammation via cytokine regulation and microbiota modulation.These preliminary findings lay a foundation for further mechanistic and applied research.
基金National Institutes of Health grants,T32AA013527,R01GM128242,and F30DK123929 supported this work.
文摘Background Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone.We sought to characterise changes in the intestinal microbiome and short-chain fatty acids(SCFAs)following alcohol intoxication and burn injury and to determine whether these changes are associated with intestinal inflammation.Methods 10–12-week-old C57BL/6 male and female mice were subjected to ethanol intoxication and a 12.5%total body surface area scald burn injury.The following day,mice were euthanised and faecal contents from the caecum and small intestine(SI)were harvested for 16S sequencing for microbial analysis and caecum contents underwent high-performance liquid chromatography mass spectroscopy to assess SCFAs.Results The intestinal microbiome of ethanol burn(EB)mice exhibited decreased alpha diversity and distinct beta diversity compared with sham vehicle(SV).EB faeces were marked by increased Proteobacteria and many pathobionts.EB caecum faeces exhibited a significant decrease in butyrate and a downward trend in acetate and total SCFAs.SCFA changes correlated with microbial changes particularly in the SI.Treatment of murine duodenal cell clone-K(MODE-K)cells with faecal slurries led to upregulation of interleukin-6(IL-6)from EB faeces compared with SV faeces which correlated with levels of Enterobacteriaceae.However,supplementation of butyrate reduced faecal slurry-induced MODE-K cells IL-6 release.Conclusion Together,these findings suggest that alcohol and burn injury induce bacterial dysbiosis and a decrease in SCFAs,which together can promote intestinal inflammation and barrier disruption,predisposing to postinjury pathology.
基金The German Research Foundation(DFG-MA 2621/5-1)the Sino German Center Mobility Programme(M-0693)the Johannes and Frieda Marohn Stiftung(Alz/lko-Matt/2022)supportedthisresearch.
文摘In a recent paper published in Nature,Oliver and colleagues report that pyloric gland metaplastic cells within the intestinal epithelium arise from crypt-based stem cells in response to chronic inflammatory irritation.These metaplastic cells to which the authors refer to as INFLAREs exhibit unique transcriptional signatures and promote inflammation-mediated tissue remodeling.
基金supported by the Deutsche Forschungsgemeinschaft:FOR 2886-TP02CRC 1181 project A01,TRR/CRC369 DIONE-501752319 projects A02 and B05 ERC consolidator ODE,Erlangen-Nuremberg University ELAN-Program P044the National Natural Science Foundation of China 82271833.
文摘Germinal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments.However,the function of hypoxia-inducible factor(HIF)-1αin immunoglobulin production remains incompletely characterized.Here,we demonstrated that B cells lacking HIF-1αexhibited significantly lower glycolytic metabolism and impaired IgA production.Loss of HIF-1αin B cells affects IgA-producing B-cell differentiation and exacerbates dextran sodium sulfate(DSS)-induced colitis.Conversely,promoting HIF-1αstabilization via a PHD inhibitor roxadustat enhances IgA class switching and alleviates intestinal inflammation.Mechanistically,HIF-1αfacilitates IgA class switching through acetyl-coenzyme A(acetyl-CoA)accumulation,which is essential for histone H3K27 acetylation at the Sαregion.Consequently,supplementation with acetyl-CoA improved defective IgA production in Hif1a-deficient B cells and limited experimental colitis.Collectively,these findings highlight the critical importance of HIF-1αin IgA class switching and the potential for targeting the HIF-1α-dependent metabolic‒epigenetic axis to treat inflammatory bowel diseases and other inflammatory disorders.
基金funded by the National Key Research and Development Program of China(numbers:2022YFA1304201 and 2021YFD1300201)the National Natural Science Foundation of China(numbers:32125036,32172750,32302765,and 32330100)+2 种基金the Beijing Municipal Natural Science Foundation(number 6232024)China Agricultural Research System(number CARS-35)2115 Talent Development Program of China Agricultural University,and the 111 Project(B16044).
文摘Background:Qiwenghuangbo powder(QP),composed of Astragalus,Phellodendron chinensis,and Radix pulsatilla,is a traditional Chinese herbal formula,but its effects on weaned piglets remained unclear.Methods:Weaned piglets fed with 0.5 kg/t QP(QP1),1 kg/t QP(QP2),low-zinc oxide(ZnO;negative control),and high-ZnO(positive control)diets in two phases,respec-tively,and the growth performance,intestinal morphology,cytokines,and microbial communities were profiled.The mouse models of colitis induced by Citrobacter roden-tium and dextran sulfate sodium(DSS)were employed to elucidate the potential role of QP-fed enriched key species.Results:Dietary 1.0 kg/t QP alleviated diarrhea and inflammation and improved intes-tinal development and growth performance of weaned piglets.Moreover,this dietary intervention notably altered microbiota composition,characterized by the enrich-ment of Limosilactobacillus reuteri.Furthermore,out of three isolated L.reuteri,two strains could alleviate pathogen infection and intestinal inflammation,respectively.Specifically,the anti-inflammatory effect of one strain was achieved by promoting the colonization resistance of C.rodentium as significantly reduced pathogen loads.The other strain mitigated DSS-induced colitis by enhancing the goblet cell function and inhibiting the secretion of pro-inflammatory cytokines,particularly interleukin-1β(IL-1ß)and tumor necrosis factor-α(TNF-α).Conclusions:Dietary QP improved the growth performance and intestinal health of weaned piglets by promoting the colonization of L.reuteri.The isolated commensal L.reuteri control colitis in a strain-specific mechanism,highlighting the potential of QP and L.reuteri in providing evidence for gut health promotion.
基金funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
文摘Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.
基金financial support of the National Natural Science Foundation of China(82370532,82341219)Shanghai Hospital Development Center Foundation(SHDC12022118)。
文摘YdjC chitooligosaccharide deacetylase homolog(YDJC)has been identified as a susceptibility gene for inflammatory bowel disease(IBD),yet its role in the pathogenesis of IBD,particularly in regulating immune responses in the gut mucosa,remains elusive.In this study,we demonstrated that YDJC expression is downregulated in inflamed mucosa,particularly in the CD4^(+)T cells of IBD patients,and that Ydjc deficiency promotes CD4^(+)T-cell proliferation and Th1 cell differentiation,thereby exacerbating acute and chronic colitis in mice.Integrative transcriptomic,proteomic,and metabolomic analyses revealed that Ydjc^(-/-)CD4^(+)T cells exhibit upregulated SREBP2-mediated cholesterol biosynthesis.Consistently,treatment with key enzyme inhibitors targeting cholesterol biosynthesis,including simvastatin,fatostatin,and AAV-sh-Srebf2,markedly suppressed CD4^(+)T-cell proliferation and Th1 cell differentiation,thereby alleviating colitis in Ydjc^(-/-)mice.Mechanistically,YDJC directly deacetylates SREBP2,which further suppresses downstream target gene expression(e.g.,Hmgcr,Hmgcs1,and Cyp51).Therefore,our findings elucidate a novel mechanism whereby YDJC restrains intestinal mucosal inflammation by downregulating SREBP2-driven Th1 cell differentiation,suggesting that targeting YDJC and SREBP2-mediated cholesterol biosynthesis may serve as promising therapeutic strategies for IBD.
