BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on ...BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.展开更多
The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α...The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α and the incremental duodenum of the elastic modulus are both larger than those of the jejunum. It means that the duodenum is more deformable than the jejunum. The experimental results of this work provide basal data for kinematics study of a robotic endoscope.展开更多
In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical techniq...In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical technique.The results showed that the NOS-pos展开更多
Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea,...Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea, vomiting, abdominal pain. The present study demonstrated that red beetroot juice (RBRJ) contains a compound or compound complex with the ability to specifically stimulate duodenal iron absorption, shown in experiments in vitro, in situ and in vivo. The effect does not depend on juice sugar and ascorbic acid concentration. Fractionated RBRJ impact on iron absorption is dose dependent. This phenomenon is described for the first time.展开更多
480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with...480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with wheat-based diet supplemented with xylanase(1.2×l0~4 U/kg diet).On day 16,two birds per replication with average live weight were selected and sacrificed.Tissue samples of jejunum and ileum were collected to detect mRNA expression of cationic amino acid transporters using RT-PCR.The results showed that xylanase significantly increased the abundance of mRNA for rBAT and CAT4 in the intestines of broilers fed with wheat-based diets(P<0.05)and had a tendency to increase the mRNA expression of y^+LAT2 and CAT1 in jejunum(P>0.05),y^+LAT2,CAT1 and CAT4 in ileum(P>0.05).The treatment had no effect on the expression of rBAT mRNA in ileum(P>0.05).展开更多
The aim of this study was to investigate the effects of rare earth elements （REEs） in preventing Hg^2＋ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2＋ , La^3...The aim of this study was to investigate the effects of rare earth elements （REEs） in preventing Hg^2＋ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2＋ , La^3＋ , the mixture of La^3＋ and Hg^2＋ and DNA by spectroscopy. The interactions between Hg^2＋ , La^3＋ , the mixture of La^3＋ and Hg^2＋ and DNA from fish intestine in vitro was investigate by using absorption spectrum and fluorescence emission spectrum. Ultraviolet absorption spectra indicated that the addition of Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ to DNA generated obvious hypochromic effect. Meanwhile, the 205.2 nm peak of DNA blue and the 258.2 nm peak of DNA red shifted. The hypochromic effect and peak shift was caused by these ions in an order of Hg^2＋ 〉 Hg^2＋ ＋ La^3＋ 〉 La^3＋ . The fluorescence emission spectra showed that as the addition of Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ , the emission peak at about 416.2 nm of DNA did not obviously change, but the fluorescence intensity reduced gradually with the order in treatment was Hg^2＋ 〉 Hg^2＋ 〉 La^3＋ 〉 La^3＋ . Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ had 1.12, 0.58, and 0.81 binding sites to DNA, the fluorescence quenching of DNA caused by them all attributed to static quenching. The binding constants KA of binding sites were 3.82×10^4 and 4.22×10^2 L·mol^-1 ; 2.50×10^4 and 2.95×10^3 L·mol^-1 ; 3.05×10^4 and 1.00×10^3 L·mol^-1. The results showed that La^3＋ could relieve destruction caused by Hg^2＋ on the DNA structure.展开更多
Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim o...Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim of this study was to investigate the expression of surfactant proteins in the intes-tines and pancreas of murine fetuses. Methods: Immunostaining for SP-A and SP-D was assessed in the small intestine and pancreas of ICR murine fetuses on days 15, 16, 17 and 18 of gestation (normal duration of pregnancy: 19 - 21 days). RT-PCR was performed to detect the expression of spa and spd mRNA in the small intestine and pancreas on day 16, 17 and 18 of gestation. Results: Immunoreactivity for SP-A and SP-D in the acinar cells of pancreas and intestinal mucosal surface were positive on day 16 of gestation onward. RT-PCR revealed that the expression of spa and spd mRNA was significant in the pancreas but weak in the small intestine. Conclusions: Our data revealed that surfactant proteins are present in the fetal intestines and pancreas and that a significant expression of spa and spd mRNA is detected in the fetal pancreas. Pancreas may be a possible organ involved in the synthesis and secretion of surfactant proteins into the intestinal lumen.展开更多
In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and his...In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5<sup>th</sup>. The fetuses were removed on the 20.5<sup>th</sup> (G-1) and 21.5<sup>th</sup> days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.展开更多
Pigs are important agricultural animals and valuable biomedical models.The intestinal tract is a crucial digestive organ and the largest immune organ.However,the function of pig intestines at single-cell resolution re...Pigs are important agricultural animals and valuable biomedical models.The intestinal tract is a crucial digestive organ and the largest immune organ.However,the function of pig intestines at single-cell resolution remains poorly understood.Here,we created single-nucleus transcriptomic maps of the ileum and cecum for wild boars,Bama Xiang pigs,and Large White pigs,aged 30,42,150,and 730 d.Our atlas revealed 19 major cell types and 58 cellular subtypes,including several previously uncharacterized cellular subtypes,such as EBF1+fibroblasts,TMEM163+macrophages,and neuron subtypes expressing FCAMR.We discovered and confirmed that ileum neurons,rather than cecum neurons,can regulate inflammatory responses,highlighting interactions of neurons with dendritic cells(DCs)and lymphatic endothelial cells(LECs)through the NAMPT-INSR ligand-receptor pair in the ileum.Microbial-derived short-chain fatty acids,such as propionic acid and acetic acid,enhanced plasma cell differentiation and humoral immune responses by upregulating XBP1 and SDC1 expression,thereby endowing wild boars with a stronger immune response than domestic pigs.We identified and validated the enterocyteenriched transcription factors FOXO1 and NR1H4 in wild boars,which contributed to the superior nutrient absorption of wild boars relative to domestic pigs.Furthermore,we comprehensively characterized the postnatal development of wild boar intestinal cells and revealed that plasma cells presented the most pronounced developmental changes.We identified highly conserved cell types and features between pig and human intestines.Overall,our work provides a foundation for improving pig feed conversion and health while also providing a reference for research on human intestinal diseases.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented...In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.展开更多
Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were...Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were transplanted heterotopically in two pigs. And after 28 days of heterotopic transplantation, the transplanted intestine was interposed into continuity of host intestine as orthotopic transplant. During the experiment, tests were made on 6th day after the first operation (period 1), the 14th (II), 28th (III) day after heterotopic transplantation, and 3 weeks after interposition (IV) respectively for the levels of glucose, palmitate and leucine. Additionally, at period I, III, and IV, a 3 cm length of intestinal mucosa was excised for morphologic observation and determination of DNA, RNA and protein contents. After heterotopic transplantation, the absorptive function of transplanted intestine was severely impaired for two weeks. The absorption of glucose! and palmitate was partially recovered by period III, at which time leucine level had return to normal. At period IV, the absorptive function of glucose and leucine had surpassed normal levels, while palmitate had risen to the level of pretransplantation. After transplantation, at period III, DNA, RNA and protein contents were well below normal. Three weeks after orthotopic transplantation, RNA and protein had risen to normal level, while DNA content remained below normal, The morphologic changes during the experiment were correlated with the changes of contents in RNA, protein and DNA. The area, height, width of villi and the area, depth, width:of crypt were below normal at III and recovered by 3 weeks after orthotopic transplantation (period IV), but were still lower than the levels at pretransplantation. Crypt depths were deeper than those of pretransplantation.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mecha...Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.展开更多
Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation...Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.展开更多
Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in dis...Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.展开更多
Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compo...Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.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
Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementat...Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.展开更多
Atopic dermatitis(AD),which is associated with inflammatory response and skin damage,is increasing worldwide in recent years.Interest is increasing in the protective effects of natural and fermented products on the pr...Atopic dermatitis(AD),which is associated with inflammatory response and skin damage,is increasing worldwide in recent years.Interest is increasing in the protective effects of natural and fermented products on the prevention and treatment of AD.This study aimed to investigate the ameliorative effects of a new rice milk product fermented with Saccharomyces cerevisiae on AD mice.Fermented rice milk could effectively attenuated the symptoms of AD mice,such as skin lesions,scaliness and lichenification.Furthermore,fermented rice milk decreased the levels of inflammatory cytokines interleukin(IL)-4,IL-6 and tumor necrosis factor(TNF)-αin 2,4-dinitrochlorobenzene(DNCB)induced mice.It was also observed that fermented rice milk treatment downregulated the levels of p-IKBα,p-NF-κB,p-ERK,p-JNK and p-p38 proteins expression in skin of AD mice,which showed the anti-inflammatory function of fermented rice milk,mainly via the NF-κB and MAPK signaling pathways.In addition,S.cerevisiae fermentation reduced original flavor of rice milk,and increased the acid and alcohol compounds.Overall,the findings indicated that S.cerevisiae fermentation improved the flavor characteristics of rice milk,and fermented rice milk exhibited protective effects against DNCB-induced atopic dermatitis by downregulating NF-κB and MAPK signaling pathways and protecting the skin barrier.展开更多
基金Supported by the National Natural Science Foundation of China,No.82174461Capacity Enhancement Program of Xiyuan Hospital,China Academy of Traditional Chinese Medicine,No.XYZX0201-22Science and Technology Innovation Project of China Academy of Traditional Chinese Medicine,No.CI2021A01811.
文摘BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.
文摘The biomechanical behavior of dog's duodenum and jejunum were studied and a formulation of the stress strain relation is presented in this paper. The results obtained indicated that the exponential coefficient α and the incremental duodenum of the elastic modulus are both larger than those of the jejunum. It means that the duodenum is more deformable than the jejunum. The experimental results of this work provide basal data for kinematics study of a robotic endoscope.
文摘In the present study,the localization of nitric oxide synthase(NOS) in the mouse intestines(duodenum,jejunum,ileum and proximal segment of large intestine) was observed using NADPH-diaphorase(ND) histochemical technique.The results showed that the NOS-pos
文摘Iron deficiency is one of the leading risk factors for disability and death worldwide. Targeted iron supplementation with pharmaceuticals is widely used, but oral iron salt ingestion often causes side effects—nausea, vomiting, abdominal pain. The present study demonstrated that red beetroot juice (RBRJ) contains a compound or compound complex with the ability to specifically stimulate duodenal iron absorption, shown in experiments in vitro, in situ and in vivo. The effect does not depend on juice sugar and ascorbic acid concentration. Fractionated RBRJ impact on iron absorption is dose dependent. This phenomenon is described for the first time.
基金supported by National Key Basic Research Development Program 973 of China(No.2004CB117501)National Natural Science Foundation of China(No.30671519)Guangdong Province Scientific Technology Research Project(No.2005B20201016)
文摘480 healthy 1-day-old male yellow-feathered chickens were selected and assigned randomly into groups A and B,each having 6 pens with 40 birds per pen.The birds in group A were fed with wheatbased diet and group B with wheat-based diet supplemented with xylanase(1.2×l0~4 U/kg diet).On day 16,two birds per replication with average live weight were selected and sacrificed.Tissue samples of jejunum and ileum were collected to detect mRNA expression of cationic amino acid transporters using RT-PCR.The results showed that xylanase significantly increased the abundance of mRNA for rBAT and CAT4 in the intestines of broilers fed with wheat-based diets(P<0.05)and had a tendency to increase the mRNA expression of y^+LAT2 and CAT1 in jejunum(P>0.05),y^+LAT2,CAT1 and CAT4 in ileum(P>0.05).The treatment had no effect on the expression of rBAT mRNA in ileum(P>0.05).
基金Project supported by the National Natural Science Foundation of China (20671067)
文摘The aim of this study was to investigate the effects of rare earth elements （REEs） in preventing Hg^2＋ pollution, using fish intestinal DNA in vitro and study the mechanism of the interactions between Hg^2＋ , La^3＋ , the mixture of La^3＋ and Hg^2＋ and DNA by spectroscopy. The interactions between Hg^2＋ , La^3＋ , the mixture of La^3＋ and Hg^2＋ and DNA from fish intestine in vitro was investigate by using absorption spectrum and fluorescence emission spectrum. Ultraviolet absorption spectra indicated that the addition of Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ to DNA generated obvious hypochromic effect. Meanwhile, the 205.2 nm peak of DNA blue and the 258.2 nm peak of DNA red shifted. The hypochromic effect and peak shift was caused by these ions in an order of Hg^2＋ 〉 Hg^2＋ ＋ La^3＋ 〉 La^3＋ . The fluorescence emission spectra showed that as the addition of Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ , the emission peak at about 416.2 nm of DNA did not obviously change, but the fluorescence intensity reduced gradually with the order in treatment was Hg^2＋ 〉 Hg^2＋ 〉 La^3＋ 〉 La^3＋ . Hg^2＋ , La^3＋ , and the mixture of La^3＋ and Hg^2＋ had 1.12, 0.58, and 0.81 binding sites to DNA, the fluorescence quenching of DNA caused by them all attributed to static quenching. The binding constants KA of binding sites were 3.82×10^4 and 4.22×10^2 L·mol^-1 ; 2.50×10^4 and 2.95×10^3 L·mol^-1 ; 3.05×10^4 and 1.00×10^3 L·mol^-1. The results showed that La^3＋ could relieve destruction caused by Hg^2＋ on the DNA structure.
文摘Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim of this study was to investigate the expression of surfactant proteins in the intes-tines and pancreas of murine fetuses. Methods: Immunostaining for SP-A and SP-D was assessed in the small intestine and pancreas of ICR murine fetuses on days 15, 16, 17 and 18 of gestation (normal duration of pregnancy: 19 - 21 days). RT-PCR was performed to detect the expression of spa and spd mRNA in the small intestine and pancreas on day 16, 17 and 18 of gestation. Results: Immunoreactivity for SP-A and SP-D in the acinar cells of pancreas and intestinal mucosal surface were positive on day 16 of gestation onward. RT-PCR revealed that the expression of spa and spd mRNA was significant in the pancreas but weak in the small intestine. Conclusions: Our data revealed that surfactant proteins are present in the fetal intestines and pancreas and that a significant expression of spa and spd mRNA is detected in the fetal pancreas. Pancreas may be a possible organ involved in the synthesis and secretion of surfactant proteins into the intestinal lumen.
文摘In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5<sup>th</sup>. The fetuses were removed on the 20.5<sup>th</sup> (G-1) and 21.5<sup>th</sup> days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.
基金supported by the National Natural Science Foundation of China(31790410)。
文摘Pigs are important agricultural animals and valuable biomedical models.The intestinal tract is a crucial digestive organ and the largest immune organ.However,the function of pig intestines at single-cell resolution remains poorly understood.Here,we created single-nucleus transcriptomic maps of the ileum and cecum for wild boars,Bama Xiang pigs,and Large White pigs,aged 30,42,150,and 730 d.Our atlas revealed 19 major cell types and 58 cellular subtypes,including several previously uncharacterized cellular subtypes,such as EBF1+fibroblasts,TMEM163+macrophages,and neuron subtypes expressing FCAMR.We discovered and confirmed that ileum neurons,rather than cecum neurons,can regulate inflammatory responses,highlighting interactions of neurons with dendritic cells(DCs)and lymphatic endothelial cells(LECs)through the NAMPT-INSR ligand-receptor pair in the ileum.Microbial-derived short-chain fatty acids,such as propionic acid and acetic acid,enhanced plasma cell differentiation and humoral immune responses by upregulating XBP1 and SDC1 expression,thereby endowing wild boars with a stronger immune response than domestic pigs.We identified and validated the enterocyteenriched transcription factors FOXO1 and NR1H4 in wild boars,which contributed to the superior nutrient absorption of wild boars relative to domestic pigs.Furthermore,we comprehensively characterized the postnatal development of wild boar intestinal cells and revealed that plasma cells presented the most pronounced developmental changes.We identified highly conserved cell types and features between pig and human intestines.Overall,our work provides a foundation for improving pig feed conversion and health while also providing a reference for research on human intestinal diseases.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金Supported by the National Key Research and Development Program of Traditional Chinese Medicine Modernization Project,China(No.2023YFC3504000)the Science and Technology Development Project of Jilin Province,China(No.20240404043ZP)the Science and Technology Innovation Cooperation Project of Changchun Science and Technology Bureau and Chinese Academy of Sciences,China(No.23SH14)。
文摘In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.
文摘Ten outbred pigs were each operated on for three times. First, a 130 cm length of terminal ileum of each pig was isolated on its vascular pedicle as a Thiry-Vella loop. One week later, the solitary ileal segments were transplanted heterotopically in two pigs. And after 28 days of heterotopic transplantation, the transplanted intestine was interposed into continuity of host intestine as orthotopic transplant. During the experiment, tests were made on 6th day after the first operation (period 1), the 14th (II), 28th (III) day after heterotopic transplantation, and 3 weeks after interposition (IV) respectively for the levels of glucose, palmitate and leucine. Additionally, at period I, III, and IV, a 3 cm length of intestinal mucosa was excised for morphologic observation and determination of DNA, RNA and protein contents. After heterotopic transplantation, the absorptive function of transplanted intestine was severely impaired for two weeks. The absorption of glucose! and palmitate was partially recovered by period III, at which time leucine level had return to normal. At period IV, the absorptive function of glucose and leucine had surpassed normal levels, while palmitate had risen to the level of pretransplantation. After transplantation, at period III, DNA, RNA and protein contents were well below normal. Three weeks after orthotopic transplantation, RNA and protein had risen to normal level, while DNA content remained below normal, The morphologic changes during the experiment were correlated with the changes of contents in RNA, protein and DNA. The area, height, width of villi and the area, depth, width:of crypt were below normal at III and recovered by 3 weeks after orthotopic transplantation (period IV), but were still lower than the levels at pretransplantation. Crypt depths were deeper than those of pretransplantation.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金financially supported by the Project of National Key R&D Program of China(2022YFD1300403)the Natural Science Foundation of Hubei Province Project(2024AFB926)Hubei Provincial Science and Technology Program(2025CSA037)。
文摘Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.
基金Leducq Trans-Atlantic Network of Excellence,Grant/Award Number:TNE-21CVD04Spanish Ministry of Science and Innovation,Grant/Award Number:PID2020-117765RB-I00 and PID2022-140616OB-I00+1 种基金Instituto de Salud Carlos III,European Development Regional Fund,RICORS-ICTUS Grant/Award Number:RD21/0006/0001the FORTALECE program.Grant/Award Number:FORT23/00023。
文摘Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
基金funding by National Natural Science Foundation of China(No.82174492)National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Project(N o.ZJJBGS2024002-1).
文摘Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.
基金funded by the National Natural Science Foundation of China(32101915)Natural Science Foundation of Jiangxi Province(20224BAB205005)+1 种基金Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province(20232BCJ23090)Natural Science Foundation of Chongqing(CSTB2023NSCQMSX0497).
文摘Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.
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The National Natural Science Foundation of China(32302759,32372924)the CAST Youth Talent Support Project-Special Program for Doctoral Students(156-O-230-0000375-5)。
文摘Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.
基金financial support received from the Shanghai Oriental Talent Youth Project(T2023218)the National Science Fund for Distinguished Young Scholars of China(32025029)+2 种基金the Young Elite Scientist Sponsorship Program of China Association for Science and Technology(YESS20220128)the Shanghai Research Center for Food Microbiology Engineering(19DZ2281100)the National Natural Science Foundation of China(Key Program)(U23A20261).
文摘Atopic dermatitis(AD),which is associated with inflammatory response and skin damage,is increasing worldwide in recent years.Interest is increasing in the protective effects of natural and fermented products on the prevention and treatment of AD.This study aimed to investigate the ameliorative effects of a new rice milk product fermented with Saccharomyces cerevisiae on AD mice.Fermented rice milk could effectively attenuated the symptoms of AD mice,such as skin lesions,scaliness and lichenification.Furthermore,fermented rice milk decreased the levels of inflammatory cytokines interleukin(IL)-4,IL-6 and tumor necrosis factor(TNF)-αin 2,4-dinitrochlorobenzene(DNCB)induced mice.It was also observed that fermented rice milk treatment downregulated the levels of p-IKBα,p-NF-κB,p-ERK,p-JNK and p-p38 proteins expression in skin of AD mice,which showed the anti-inflammatory function of fermented rice milk,mainly via the NF-κB and MAPK signaling pathways.In addition,S.cerevisiae fermentation reduced original flavor of rice milk,and increased the acid and alcohol compounds.Overall,the findings indicated that S.cerevisiae fermentation improved the flavor characteristics of rice milk,and fermented rice milk exhibited protective effects against DNCB-induced atopic dermatitis by downregulating NF-κB and MAPK signaling pathways and protecting the skin barrier.
