Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a se...Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.展开更多
Dietary sanguinarine(SAN)can enhance the growth performance of poultry and livestock,but the regulatory mechanism of the SAN monomer on intestinal homeostasis and how it promotes growth performance has not yet been cl...Dietary sanguinarine(SAN)can enhance the growth performance of poultry and livestock,but the regulatory mechanism of the SAN monomer on intestinal homeostasis and how it promotes growth performance has not yet been clarified.In this study,200 chickens were divided into four groups and fed different doses of SAN(0,0.225,0.75,2.25 mg/kg)for transcriptome and microbiota analysis.The data showed that different doses of SAN supplementation increased the feed conversion rate(FCR)of 22 to 42 d old and 1 to 42 d old broilers(P<0.01),and 0.225 mg/kg SAN reduced the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA)and blood urea nitrogen(BUN)in serum(P<0.01).Dietary SAN increased the villus height and the villus height/crypt depth(V/C)ratio in the ileum(P<0.01).The levels of tight junction proteins(zonula occludens-1,occludin and claudin-1)were up-regulated in the ileum and cecum(P<0.01)and the levels of immunoglobulin(Ig)A,IgM,IgG,interleukin(IL)-4,IL-10 and interferon(IFN)-γ were up-regulated in the serum and ileum(P<0.01).RNA-seq analysis revealed 385 differentially expressed genes(DEGs)(|log_(2) fold change|>1,FDR<0.05)between the SAN group and CON group.Kyoto Encyclopedia of Genes and Genomes pathway analysis showed 15 pathways mostly associated with the immune system.Additionally,the reverse transcription-PCR results showed that the relative mRNA expression of β-defensin and mucin 2 were upregulated(P<0.01)and Toll-like receptor(TLR2 and TLR4)mRNA expression were down-regulated by SAN(P<0.01),which was consistent with the transcriptomic analysis.Western blot analysis also showed that SAN reduced the expression of inflammatory proteins such as TLR4,nuclear factor-kappa B and IL-1β in the ileum(P<0.01).In addition,at the genus level,SAN significantly increased the relative abundance of bacteria(Bacteroides,unclassified_f__Lachnospiraceae,Lactobacillus and Romboutsia)involved in acetate and butyrate production in the cecum,which are associated with enhanced intestinal immune function and maintaining intestinal health.In conclusion,SAN ameliorates the growth performance of broilers,enhances intestinal immune function,regulates the structure of microbiota and maintains intestinal health.展开更多
Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the produ...Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the production of tryptophan metabolites.Sanguinarine(SAN)enhances broiler immunity,however,its low bioavailability and underlying mechanisms remain unclear.This study aimed to decode the mechanisms by which sanguinarine enhances intestinal immune function in broilers.Methods Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to identify the main metabolites of sanguinarine in the intestine.Subsequently,equal concentrations of sanguinarine and its metabolites were separately added to the diets.The effects of sanguinarine and its metabolites on the intestinal immune function of broiler chickens were evaluated using 16S rRNA gene amplicon sequencing and tryptophan metabolomics approaches.Results We determined that dihydrosanguinarine(DHSA)is the main metabolite of sanguinarine in the intestine.Both compounds increased average daily gain and reduced feed efficiency,thereby improving growth performance.They also enhanced ileal villus height and the villus-to-crypt(V/C)ratio while decreasing crypt depth and upregulating the mRNA expression of tight junction proteins ZO-1,occludin and claudin-1.Furthermore,both compounds promoted the proliferation of intestinal Lactobacillus species,a tryptophan-metabolizing bacterium,stimulated short-chain fatty acid production,and lowered intestinal pH.They regulated tryptophan metabolism by increasing the diversity and content of indole tryptophan metabolites,activating the aryl hydrocarbon receptor(AhR)pathway,and elevating the mRNA levels of CYP1A1,CYP1B1,SLC3A1,IDO2 and TPH1.Inflammatory cytokines IL-1β and IL-6 were inhibited,while anti-inflammatory cytokines IL-10 and IL-22,serum SIgA concentration,and intestinal MUC2 expression were increased.Notably,DHSA exhibited a more pronounced effect on enhancing immune function compared to SAN.Conclusions SAN is converted to DHSA in vivo,which increases its bioavailability.DHSA regulates tryptophan metabolism by activating the AhR pathway and modulating immune-related factors through changes in the gut microbiota.Notably,DHSA significantly increases the abundance of Lactobacillus,a key tryptophan-metabolizing bacterium,thereby enhancing intestinal immune function and improving broiler growth performance.展开更多
The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by ...The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.展开更多
[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural ...[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.展开更多
Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previo...Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.展开更多
AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of...AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response.展开更多
[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body＇s immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secret...[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body＇s immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secretory type immune globulin cell A were dynamic observed to research chicken immune organ growth with histology conventional slice technology and immunohistochemistry dye. 1 day age healthy roosters were divided into 3 groups： the group 3 was control group. 1% and 0.5% concentration of Chinese herbal medicine immunopotentiator drinking water were added in the group 1 and 2 in continuous 60 d. The immune organ index was determined every 12 d and the histotomy of chicken small intes- tine in group control and 1% were taken for histological observation on day 24, 36 and 48. [ Result] Treatment group immune organ index was significantly higher than that of the control group and 1% group of small intestinal villus inherent intraformational immune cells number significantly increased （P〈0.01） compared with controls. Day 36 age group and day 48 group immune cells were higher than day 24 group of cell number （P〈 0.01 ）. [ Conclusionl Chinese medicinal herb had obvious role in promoting chicken immune organ growth and obvious influence on the quantity change of the intestinal mucosal immune cells.展开更多
The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent stud...The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.展开更多
Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an I...Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an IgAN disease model,and were randomly divided into IgAN group,IgAN+Cur(150 mg/kg)group and IgAN+Cur(300 mg/kg)group using simple randomisation.展开更多
AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-b...AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.展开更多
Hirsutella sinensis(H.sinensis),a substitute for a valuable edible and medicinal fungus,Cordyceps sinensis,is well known for its various of beneficial pharmacological properties.However,research on the effects of H.si...Hirsutella sinensis(H.sinensis),a substitute for a valuable edible and medicinal fungus,Cordyceps sinensis,is well known for its various of beneficial pharmacological properties.However,research on the effects of H.sinensis on colitis in mice is limited.In our previous studies,we carried out a systematic classification and structural identification of the polysaccharides in H.sinensis.Here,we utilized a murine model of colitis induced by a 3%dextran sulfate sodium(DSS)administration to investigate the protective effects of the H.sinensis myceliumderived starch-like polysaccharide(HSWP-1a)on colitis.Our findings demonstrate that HSWP-1a effectively mitigates DSS-induced weight loss,reduces colon tissue damage,increases tight junction protein expression,and restores intestinal barrier function.Notably,during this process,HSWP-1a reversed the DSS-induced increase in M1/M2 macrophage polarization and the Th17/Treg cell balance,ameliorating the DSS-induced decrease in antiinflammatory cytokine expression while inhibiting the DSS-induced increase in proinflammatory cytokine levels and mediating immune tolerance to maintain local intestinal immune homeostasis.Furthermore,HSWP-1a is capable of regulating the intestinal microbiota,enhancing the abundance of beneficial bacteria such as Lachnospiraceae_NK4A136_group,and reducing the abundance of harmful bacteria like Proteobacteria and Cyanobacteria.HSWP-1a also restores the levels of short-chain fatty acids(SCFA)to maintain the balanced intestinal microenvironment.Overall,HSWP-1a achieves its colitis-protective effects through its ability to strengthen the intestinal barrier,regulate the immune system,and restore gut microbiota interactions.These findings suggest that HSWP-1a has potential as a valuable food supplement or nutritional health product for alleviating colitis.展开更多
The form of folate in the maternal diet,whether as synthetic folic acid(FA)from fortified foods or as bioactive folate(5-methyltetrahydrofolate,5-MTHF),may differentially influence offspring development.This study com...The form of folate in the maternal diet,whether as synthetic folic acid(FA)from fortified foods or as bioactive folate(5-methyltetrahydrofolate,5-MTHF),may differentially influence offspring development.This study compared their effects on one-carbon metabolism and intestinal immune programming in a mouse model.Dams were fed FA-or 5-MTHF-based diets during pregnancy and lactation.In offspring,5-MTHF enhanced intestinal one-carbon flux,elevating S-adenosylmethionine levels and global DNA methylation compared to FA.This metabolic-epigenetic shift was associated with downregulated expression of T-cell activation pathways and reduced proportions of Th2 and Th17 cells in mesenteric lymph nodes.In vitro,5-MTHF directly suppressed Th2 cell differentiation.These results demonstrate that the chemical form of folate is a critical factor in early-life metabolic and immune programming.The findings highlight the importance of considering nutrient forms in maternal dietary patterns during pregnancy and lactation,providing a basis for the development of related functional foods and the evaluation of precision nutrition strategies.展开更多
Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominan...Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominant structures and major fermentable substrates for microbial production of short-chain fatty acids(SCFAs).To elucidate the downstream immunomodulatory actions of HMOs,this study specifically examined their principal microbial metabolites—SCFAs(acetate,propionate,and butyrate)—which function as central mediators of intestinal barrier integrity and immune homeostasis.This study investigated the protective effects and molecular mechanisms of SCFAs—particularly butyrate—against lipopolysaccharide(LPS)-induced intestinal mucosal immune injury.In a humanized rat model,SCFAs supplementation(acetate,propionate,and butyrate)markedly alleviated body weight loss,reduced disease activity index(DAI)and histological damage,and decreased myeloperoxidase(MPO)activity.SCFAs improved intestinal barrier integrity by upregulating Claudin-1,Claudin-2,ZO-1,and Muc2 expression,while reducing serum D-lactate and diamine oxidase(DAO)levels.They also suppressed pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2)and enhanced anti-inflammatory cytokines(IL-10,IL-4)and secretory IgA(sIgA)production.Transcriptomic and protein-protein interaction(PPI)analyses revealed that butyrate modulated colonic gene expression enriched in G protein-coupled receptor signaling and IgA immune network pathways,and mitigated inflammation by inhibiting the EGFR/STAT1/CXCL10/CCL2 and IL-6/STAT3 signaling axes.In vitro,butyrate significantly reduced lactate dehydrogenase(LDH)release,downregulated inflammatory gene expression,and inhibited M1 macrophage polarization.Collectively,these findings indicate that HMOs confer intestinal immunoprotective effects primarily through the microbial metabolite butyrate,providing new mechanistic insights into the immunomodulatory potential of HMOs and supporting their development as functional food ingredients.展开更多
Dictyophora indusiate(DI)contains numerous bioactive compounds with immunomodulatory properties.However,the functional activities of its protein hydrolysate and their mechanisms of action in the regulation of systemic...Dictyophora indusiate(DI)contains numerous bioactive compounds with immunomodulatory properties.However,the functional activities of its protein hydrolysate and their mechanisms of action in the regulation of systemic and intestinal mucosal immunity remain poorly understood.This study comprehensively evaluated the immunomodulatory potential of D.indusiate peptide hydrolysate(DIPH)using a multi-omics approach.LC-MS/MS analysis showed that DIPH is composed of peptides containing 8 to 20 amino acid residues,with branchedchain amino acids comprising 20.53%of the total,and exhibits primarily hydrophobic properties.In cyclophosphamide-induced immunosuppressed mice,DIPH exhibited broad restorative effects on immunity via three interrelated mechanisms.Firstly,systemic immune function was enhanced,as demonstrated by significant elevations in serum IgG and IgM levels,and an improvement(4.5-fold)in carbon clearance capacity.Secondly,intestinal barrier integrity was strengthened through the upregulation of tight junction proteins,a 24.7%rise in goblet cells,and a 1.11-fold increase in secretory IgA production.Thirdly,DIPH administration modulated gut microbiota composition,significantly enriching beneficial bacteria including Bifidobacterium and Roseburia while reducing Streptococcus,which was accompanied by a 2.1-fold increase in butyrate production.At the molecular level,DIPH exerted its effects through dual regulatory mechanisms:suppression of the TLR4/MyD88/NF-κB pathway and activation of FoxO1-mediated mucosal restoration.These insights collectively establish DIPH as a multi-target edible fungi-derived immunomodulator that uniquely integrates gut microbiota regulation,systemic immune enhancement,and intestinal barrier restoration,highlighting its promising applications in functional food development and microbiome-targeted therapies.展开更多
This study aimed to investigate the effects of ginger straw as a replacement of peanut straw on the growth,meat quality,rumen fermentation,and immunity of goats.In this study,40 Huanghuai male goats,weighing 30±0...This study aimed to investigate the effects of ginger straw as a replacement of peanut straw on the growth,meat quality,rumen fermentation,and immunity of goats.In this study,40 Huanghuai male goats,weighing 30±0.5 kg at six months of age,were selected and randomly divided into four treatments:ginger straw 0%(G0),5%(G5),10%(G10)and 20%(G20)replacing peanut straw,with 10 goats in each treatment.Goat dry matter intake(DMI)improved as the proportion of peanut straws replaced with ginger straws increased(linear,P<0.001,quadratic,P<0.001).The highest average daily gain(ADG)and the lowest feed-to-gain ratio(F/G)were observed in G5 goats(P<0.001).The digestibilities of neutral detergent fibre(NDF,P=0.031)and acid detergent fibre(ADF,P=0.014)were higher in the G5 group than in G10 and G20.With increasing ginger straw replacement,the plasma interleukin-10(IL-10)levels increased(linear,P=0.035,quadratic,P=0.041).The microbial protein(MCP)increased as the proportion of ginger straw increased(linear,P=0.034,quadratic,P=0.041).The butyrate was increased(linear,P=0.028,quadratic,P=0.035)at all levels of ginger straw inclusion into the diet.A linear(P<0.001)increase in the height of the jejunal mucosal villi was observed as the proportion of ginger straw in the diet increased.The tight junction protein 1(TJP1)and claudin-1 mRNA expression in the jejunal mucosa were significantly higher in groups G5,G10,and G20 than in the G0 group(P<0.001).In general,substituting peanut straw with ginger straw in goat diets promoted rumen fermentation and produced more volatile fatty acids and microbial proteins to meet the needs of goats for improved growth performance.Substituting ginger straw for peanut straw improved immunity and the intestinal barrier in goats and did not adversely affect meat quality.Replacing peanut straw with 5%ginger straw in the goat diet resulted in higher NDF digestibility and growth performance.Therefore,the replacement of peanut straw with 5%ginger straw in goat diets is recommended.展开更多
With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal m...With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.展开更多
Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of acti...Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.展开更多
At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at...At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet＇s intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond ＂appropriately＂ to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.展开更多
基金supported by the grants from the Sichuan Science and Technology Program,China(No.2023NSFSC0614,2022YFS0624)grant from Science and Technology Program of Luzhou,China(No.21CGZHPT0001,2022-YJY-127)+1 种基金grant from Southwest Medical University,China(No.2021ZKZD017)grant from The Open Research Project Program of the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao),China(SKL-QRCM-OP21006).
文摘Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.
基金funded by National Key R&D Program of China(2023YFD1301200)the science and technology innovation Program of Hunan Province(2021RC3091).
文摘Dietary sanguinarine(SAN)can enhance the growth performance of poultry and livestock,but the regulatory mechanism of the SAN monomer on intestinal homeostasis and how it promotes growth performance has not yet been clarified.In this study,200 chickens were divided into four groups and fed different doses of SAN(0,0.225,0.75,2.25 mg/kg)for transcriptome and microbiota analysis.The data showed that different doses of SAN supplementation increased the feed conversion rate(FCR)of 22 to 42 d old and 1 to 42 d old broilers(P<0.01),and 0.225 mg/kg SAN reduced the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA)and blood urea nitrogen(BUN)in serum(P<0.01).Dietary SAN increased the villus height and the villus height/crypt depth(V/C)ratio in the ileum(P<0.01).The levels of tight junction proteins(zonula occludens-1,occludin and claudin-1)were up-regulated in the ileum and cecum(P<0.01)and the levels of immunoglobulin(Ig)A,IgM,IgG,interleukin(IL)-4,IL-10 and interferon(IFN)-γ were up-regulated in the serum and ileum(P<0.01).RNA-seq analysis revealed 385 differentially expressed genes(DEGs)(|log_(2) fold change|>1,FDR<0.05)between the SAN group and CON group.Kyoto Encyclopedia of Genes and Genomes pathway analysis showed 15 pathways mostly associated with the immune system.Additionally,the reverse transcription-PCR results showed that the relative mRNA expression of β-defensin and mucin 2 were upregulated(P<0.01)and Toll-like receptor(TLR2 and TLR4)mRNA expression were down-regulated by SAN(P<0.01),which was consistent with the transcriptomic analysis.Western blot analysis also showed that SAN reduced the expression of inflammatory proteins such as TLR4,nuclear factor-kappa B and IL-1β in the ileum(P<0.01).In addition,at the genus level,SAN significantly increased the relative abundance of bacteria(Bacteroides,unclassified_f__Lachnospiraceae,Lactobacillus and Romboutsia)involved in acetate and butyrate production in the cecum,which are associated with enhanced intestinal immune function and maintaining intestinal health.In conclusion,SAN ameliorates the growth performance of broilers,enhances intestinal immune function,regulates the structure of microbiota and maintains intestinal health.
基金funded by National Key R&D Program of China(2023YFD1301200)the science and technology innovation Program of Hunan Province(2021RC3091).
文摘Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the production of tryptophan metabolites.Sanguinarine(SAN)enhances broiler immunity,however,its low bioavailability and underlying mechanisms remain unclear.This study aimed to decode the mechanisms by which sanguinarine enhances intestinal immune function in broilers.Methods Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to identify the main metabolites of sanguinarine in the intestine.Subsequently,equal concentrations of sanguinarine and its metabolites were separately added to the diets.The effects of sanguinarine and its metabolites on the intestinal immune function of broiler chickens were evaluated using 16S rRNA gene amplicon sequencing and tryptophan metabolomics approaches.Results We determined that dihydrosanguinarine(DHSA)is the main metabolite of sanguinarine in the intestine.Both compounds increased average daily gain and reduced feed efficiency,thereby improving growth performance.They also enhanced ileal villus height and the villus-to-crypt(V/C)ratio while decreasing crypt depth and upregulating the mRNA expression of tight junction proteins ZO-1,occludin and claudin-1.Furthermore,both compounds promoted the proliferation of intestinal Lactobacillus species,a tryptophan-metabolizing bacterium,stimulated short-chain fatty acid production,and lowered intestinal pH.They regulated tryptophan metabolism by increasing the diversity and content of indole tryptophan metabolites,activating the aryl hydrocarbon receptor(AhR)pathway,and elevating the mRNA levels of CYP1A1,CYP1B1,SLC3A1,IDO2 and TPH1.Inflammatory cytokines IL-1β and IL-6 were inhibited,while anti-inflammatory cytokines IL-10 and IL-22,serum SIgA concentration,and intestinal MUC2 expression were increased.Notably,DHSA exhibited a more pronounced effect on enhancing immune function compared to SAN.Conclusions SAN is converted to DHSA in vivo,which increases its bioavailability.DHSA regulates tryptophan metabolism by activating the AhR pathway and modulating immune-related factors through changes in the gut microbiota.Notably,DHSA significantly increases the abundance of Lactobacillus,a key tryptophan-metabolizing bacterium,thereby enhancing intestinal immune function and improving broiler growth performance.
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)the Science and Technology Projects of Xiamen Science and Technology Bureau(3502Z20183034)。
文摘The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.
基金National Natural Science Foundation of China(31602099)Key Laboratory of Prevention and Control Agents for Animal Bacteriosis(Ministry of Agriculture)(KLPCAAB-2018-06)the Engineering Research Center of Ecology and Agricultural Use of Wetland,Ministry of Education(KF201913)。
文摘[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.
基金financially supported by the National Natural Science Foundation of China(Grant No.31972580 and U21A20252)the China Agriculture Research System(CARS-35)+1 种基金the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022C002)the Support Project of Young Leading Talents of Northeast Agricultural University(NEAU2023QNLJ-017)。
文摘Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.
基金Supported by National Natural Science Foundation of China, No. 81001549National Basic Research Program of China (973 program), No. 2009CB522900+1 种基金Shanghai Health System of Outstanding Young Talent Cultivation Program, No. XYQ2011068Shanghai Rising-Star Program, No. 10QA1406100
文摘AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response.
基金Funded the Project of Science and Technology in Hebei Province(08820412D,12820408D,12820421DShi-jiazhuang City Science and Technology Bureau Project(07150193A)Hebei Normal University of Science&Technolo-gy Doctor Fund(2007YB002)
文摘[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body＇s immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secretory type immune globulin cell A were dynamic observed to research chicken immune organ growth with histology conventional slice technology and immunohistochemistry dye. 1 day age healthy roosters were divided into 3 groups： the group 3 was control group. 1% and 0.5% concentration of Chinese herbal medicine immunopotentiator drinking water were added in the group 1 and 2 in continuous 60 d. The immune organ index was determined every 12 d and the histotomy of chicken small intes- tine in group control and 1% were taken for histological observation on day 24, 36 and 48. [ Result] Treatment group immune organ index was significantly higher than that of the control group and 1% group of small intestinal villus inherent intraformational immune cells number significantly increased （P〈0.01） compared with controls. Day 36 age group and day 48 group immune cells were higher than day 24 group of cell number （P〈 0.01 ）. [ Conclusionl Chinese medicinal herb had obvious role in promoting chicken immune organ growth and obvious influence on the quantity change of the intestinal mucosal immune cells.
文摘The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.
文摘Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an IgAN disease model,and were randomly divided into IgAN group,IgAN+Cur(150 mg/kg)group and IgAN+Cur(300 mg/kg)group using simple randomisation.
基金Supported by A grant from Nestec Ltd,Vevey,Switzerland
文摘AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.
基金The Department of Science and Technology of Jilin Province(Grant No.YDZJ202501ZYTS757,20240101247JC)the Innovation Platform Program of Qinghai Province(Grant No.2021-ZJ-T02).
文摘Hirsutella sinensis(H.sinensis),a substitute for a valuable edible and medicinal fungus,Cordyceps sinensis,is well known for its various of beneficial pharmacological properties.However,research on the effects of H.sinensis on colitis in mice is limited.In our previous studies,we carried out a systematic classification and structural identification of the polysaccharides in H.sinensis.Here,we utilized a murine model of colitis induced by a 3%dextran sulfate sodium(DSS)administration to investigate the protective effects of the H.sinensis myceliumderived starch-like polysaccharide(HSWP-1a)on colitis.Our findings demonstrate that HSWP-1a effectively mitigates DSS-induced weight loss,reduces colon tissue damage,increases tight junction protein expression,and restores intestinal barrier function.Notably,during this process,HSWP-1a reversed the DSS-induced increase in M1/M2 macrophage polarization and the Th17/Treg cell balance,ameliorating the DSS-induced decrease in antiinflammatory cytokine expression while inhibiting the DSS-induced increase in proinflammatory cytokine levels and mediating immune tolerance to maintain local intestinal immune homeostasis.Furthermore,HSWP-1a is capable of regulating the intestinal microbiota,enhancing the abundance of beneficial bacteria such as Lachnospiraceae_NK4A136_group,and reducing the abundance of harmful bacteria like Proteobacteria and Cyanobacteria.HSWP-1a also restores the levels of short-chain fatty acids(SCFA)to maintain the balanced intestinal microenvironment.Overall,HSWP-1a achieves its colitis-protective effects through its ability to strengthen the intestinal barrier,regulate the immune system,and restore gut microbiota interactions.These findings suggest that HSWP-1a has potential as a valuable food supplement or nutritional health product for alleviating colitis.
基金support from the National Key Research and Development Program of China(2024YFF1105905)the Key Project of Natural Science Foundation of Jiangxi Province(20232ACB205022)the Chinese Institute of Food Science and Technology Food Science and Technology Fund-Abbott Food Nutrition and Safety Special Research Fund(CAJJ-1).
文摘The form of folate in the maternal diet,whether as synthetic folic acid(FA)from fortified foods or as bioactive folate(5-methyltetrahydrofolate,5-MTHF),may differentially influence offspring development.This study compared their effects on one-carbon metabolism and intestinal immune programming in a mouse model.Dams were fed FA-or 5-MTHF-based diets during pregnancy and lactation.In offspring,5-MTHF enhanced intestinal one-carbon flux,elevating S-adenosylmethionine levels and global DNA methylation compared to FA.This metabolic-epigenetic shift was associated with downregulated expression of T-cell activation pathways and reduced proportions of Th2 and Th17 cells in mesenteric lymph nodes.In vitro,5-MTHF directly suppressed Th2 cell differentiation.These results demonstrate that the chemical form of folate is a critical factor in early-life metabolic and immune programming.The findings highlight the importance of considering nutrient forms in maternal dietary patterns during pregnancy and lactation,providing a basis for the development of related functional foods and the evaluation of precision nutrition strategies.
基金supported by the Hohhot City"Government,Industry,University,Research,Promotion and Application of Silver"Innovation Consortium Project(2023RC-Consortium-7)the"Lutein/DHA-caseinalgal ternary composite small intestine-targeted controlled-release system and its application in eye-protecting functional food"Project(2025YFHH0187)the"Special Funding Project of the China Post-doctoral Science Foundation"(2025T180813).
文摘Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominant structures and major fermentable substrates for microbial production of short-chain fatty acids(SCFAs).To elucidate the downstream immunomodulatory actions of HMOs,this study specifically examined their principal microbial metabolites—SCFAs(acetate,propionate,and butyrate)—which function as central mediators of intestinal barrier integrity and immune homeostasis.This study investigated the protective effects and molecular mechanisms of SCFAs—particularly butyrate—against lipopolysaccharide(LPS)-induced intestinal mucosal immune injury.In a humanized rat model,SCFAs supplementation(acetate,propionate,and butyrate)markedly alleviated body weight loss,reduced disease activity index(DAI)and histological damage,and decreased myeloperoxidase(MPO)activity.SCFAs improved intestinal barrier integrity by upregulating Claudin-1,Claudin-2,ZO-1,and Muc2 expression,while reducing serum D-lactate and diamine oxidase(DAO)levels.They also suppressed pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2)and enhanced anti-inflammatory cytokines(IL-10,IL-4)and secretory IgA(sIgA)production.Transcriptomic and protein-protein interaction(PPI)analyses revealed that butyrate modulated colonic gene expression enriched in G protein-coupled receptor signaling and IgA immune network pathways,and mitigated inflammation by inhibiting the EGFR/STAT1/CXCL10/CCL2 and IL-6/STAT3 signaling axes.In vitro,butyrate significantly reduced lactate dehydrogenase(LDH)release,downregulated inflammatory gene expression,and inhibited M1 macrophage polarization.Collectively,these findings indicate that HMOs confer intestinal immunoprotective effects primarily through the microbial metabolite butyrate,providing new mechanistic insights into the immunomodulatory potential of HMOs and supporting their development as functional food ingredients.
基金supported by the National Key R&D Pro-gram of China(2023YFD1600503)the Key Research and Development Project of Jiangxi Province(20192ACB60008).
文摘Dictyophora indusiate(DI)contains numerous bioactive compounds with immunomodulatory properties.However,the functional activities of its protein hydrolysate and their mechanisms of action in the regulation of systemic and intestinal mucosal immunity remain poorly understood.This study comprehensively evaluated the immunomodulatory potential of D.indusiate peptide hydrolysate(DIPH)using a multi-omics approach.LC-MS/MS analysis showed that DIPH is composed of peptides containing 8 to 20 amino acid residues,with branchedchain amino acids comprising 20.53%of the total,and exhibits primarily hydrophobic properties.In cyclophosphamide-induced immunosuppressed mice,DIPH exhibited broad restorative effects on immunity via three interrelated mechanisms.Firstly,systemic immune function was enhanced,as demonstrated by significant elevations in serum IgG and IgM levels,and an improvement(4.5-fold)in carbon clearance capacity.Secondly,intestinal barrier integrity was strengthened through the upregulation of tight junction proteins,a 24.7%rise in goblet cells,and a 1.11-fold increase in secretory IgA production.Thirdly,DIPH administration modulated gut microbiota composition,significantly enriching beneficial bacteria including Bifidobacterium and Roseburia while reducing Streptococcus,which was accompanied by a 2.1-fold increase in butyrate production.At the molecular level,DIPH exerted its effects through dual regulatory mechanisms:suppression of the TLR4/MyD88/NF-κB pathway and activation of FoxO1-mediated mucosal restoration.These insights collectively establish DIPH as a multi-target edible fungi-derived immunomodulator that uniquely integrates gut microbiota regulation,systemic immune enhancement,and intestinal barrier restoration,highlighting its promising applications in functional food development and microbiome-targeted therapies.
基金supported by the Anhui Provincial Science and Technology Major Project(17030701059)Special Development Funding Program(tzy202211)High-level Talents Introduction Project of Anhui Science and Technology University(DKYJ202303).
文摘This study aimed to investigate the effects of ginger straw as a replacement of peanut straw on the growth,meat quality,rumen fermentation,and immunity of goats.In this study,40 Huanghuai male goats,weighing 30±0.5 kg at six months of age,were selected and randomly divided into four treatments:ginger straw 0%(G0),5%(G5),10%(G10)and 20%(G20)replacing peanut straw,with 10 goats in each treatment.Goat dry matter intake(DMI)improved as the proportion of peanut straws replaced with ginger straws increased(linear,P<0.001,quadratic,P<0.001).The highest average daily gain(ADG)and the lowest feed-to-gain ratio(F/G)were observed in G5 goats(P<0.001).The digestibilities of neutral detergent fibre(NDF,P=0.031)and acid detergent fibre(ADF,P=0.014)were higher in the G5 group than in G10 and G20.With increasing ginger straw replacement,the plasma interleukin-10(IL-10)levels increased(linear,P=0.035,quadratic,P=0.041).The microbial protein(MCP)increased as the proportion of ginger straw increased(linear,P=0.034,quadratic,P=0.041).The butyrate was increased(linear,P=0.028,quadratic,P=0.035)at all levels of ginger straw inclusion into the diet.A linear(P<0.001)increase in the height of the jejunal mucosal villi was observed as the proportion of ginger straw in the diet increased.The tight junction protein 1(TJP1)and claudin-1 mRNA expression in the jejunal mucosa were significantly higher in groups G5,G10,and G20 than in the G0 group(P<0.001).In general,substituting peanut straw with ginger straw in goat diets promoted rumen fermentation and produced more volatile fatty acids and microbial proteins to meet the needs of goats for improved growth performance.Substituting ginger straw for peanut straw improved immunity and the intestinal barrier in goats and did not adversely affect meat quality.Replacing peanut straw with 5%ginger straw in the goat diet resulted in higher NDF digestibility and growth performance.Therefore,the replacement of peanut straw with 5%ginger straw in goat diets is recommended.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)the National Natural Science Foundation(31872904)。
文摘With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.
基金supported by College Student Innovation and Entrepreneurship Training(202110069122)Tianjin Key R&D Plan-Key Projects Supported by Science and Technology(19YFZCSN00010)Tianjin Agricultural Science and Technology Achievements Transformation and Promotion Project(202101120)。
文摘Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.
文摘At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet＇s intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond ＂appropriately＂ to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.
