This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid acc...This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.展开更多
Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects ...Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.展开更多
The effects of dietary probiotic supplementation with viable Bacillus subtilis and Bacillus amyloliquefaciens spores on sow performance,immunity,gut functional status and biofilm formation by probiotic bacteria in pig...The effects of dietary probiotic supplementation with viable Bacillus subtilis and Bacillus amyloliquefaciens spores on sow performance,immunity,gut functional status and biofilm formation by probiotic bacteria in piglets at weaning were investigated.Ninety-six sows reared in a continuous farrowing system for one full cycle were fed gestation diets during the first 90 d of pregnancy and lactation diets until the end of lactation.The sows were fed a basal diet without probiotics(control;n=48)or a diet supplemented with viable spores(1.1×10^(9)CFU/kg of feed)(probiotic;n=48).At 7 d of age,sucking piglets(n=12/group)were provided prestarter creep feed until weaning at 28 d of age.The piglets in the probiotic group were supplemented with the same probiotic and dosage as their dams.Blood and colostrum collected from sows and ileal tissues collected from piglets on the day of weaning were used for analyses.Probiotics increased the weight of piglets(P=0.077),improved the weaning weight(P=0.039)and increased both the total creep feed consumption(P=0.027)and litter gain(P=0.011).Probiotics also improved the faecal score in the second(P=0.013)week of life.The immunoglobulin G(IgG)concentrations in sow blood at farrowing and the IgM concentrations in piglet blood at weaning were higher in the probiotic group than in the control group(P=0.046).The piglets from the probiotic-treated sows showed a higher IgM concentration in the ileal mucosa(P=0.050)and a lower IgG concentration in the ileal mucosa(P=0.021)compared with the piglets from control sows.The probiotic-treated piglets had a thicker ileal mucosa(P=0.012)due to the presence of longer villi and larger Peyer's patches(P<0.001).B.subtilis and B.amyloliquefaciens were detected in the probiotic-treated piglets but not the control piglets;these bacteria were present in the digesta and villus structures and formed structures resembling biofilms.Overall,Bacillus-based probiotic supplementation improves the health indices of sows and their piglets.展开更多
Two studies were conducted to investigate the effect of Bacillus amyloliquefaciens CECr 5940(BA)as a probiotic on growth performance,amino acid digestibility and bacteria population in broiler chickens under a subclin...Two studies were conducted to investigate the effect of Bacillus amyloliquefaciens CECr 5940(BA)as a probiotic on growth performance,amino acid digestibility and bacteria population in broiler chickens under a subclinical necrotic enteritis(NE)challenge and/or fed diets with different levels of crude protein(CP).Both studies consisted of a 2×2 factorial arrangement of treatments with 480 Ross 308 mix-sexed broiler chickens.In study 1,treatments included 1)NE challenge(+/),and 2)BA(1.0×106 CFU/g of feed)supplementation(+/-).In study 2,all birds were under NE challenge,and treatments were 1)CP level(Standard/Reduced[2%less than standard])and 2)BA(1.0×106 CFU/g of feed)supplementation(+/-).After inducing NE infection,blood samples were taken on d 16 for uric acid evaluation,and cecal samples were collected for bacterial enumeration.In both studies,ileal digesta was collected on d 35 for nutrient digestibility evaluation.In study 1,the NE challenge reduced body weight gain(BWG),supressed feed conversion ratio(FCR)and serum uric acid levels(P<0.001).Supplementation of BA increased BWG(P<0.001)and reduced FCR(P=0.043)across dietary treatments,regardless of challenge.Bacillus(P=0.030)and Ruminococcus(P=0.029)genomic DNA copy numbers and concentration of butyrate(P=0.017)were higher in birds fed the diets supplemented with BA.In study 2,reduced protein(RCP)diets decreased BWG(P=0.010)and uric acid levels in serum(P<0.001).Supplementation of BA improved BWG(P=0.001)and FCR(P=0.005)and increased Ruminococcus numbers(P=0.018)and butyrate concentration(P=0.033)in the ceca,regardless of dietary CP level.Further,addition of BA reduced Clostridium perfringens numbers only in birds fed with RCP diets(P=0.039).At d 35,BA sup-plemented diets showed higher apparent ileal digestibility of cystine(P=0.013),valine(P=0.020),and lysine(P=0.014).In conclusion,this study suggests positive effects of BA supplementation in broiler diets via modulating gut microflora and improving nutrient uptake.展开更多
AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection...AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.展开更多
BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome prolifer...BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.展开更多
Objective. To study the characteristics and pathogenesis of gut barrier damage following multiple firearm injuries in a porcine model. Methods. Twenty four small pigs were divided into 4 groups: control group (n=6, gr...Objective. To study the characteristics and pathogenesis of gut barrier damage following multiple firearm injuries in a porcine model. Methods. Twenty four small pigs were divided into 4 groups: control group (n=6, group C), group H (n=6, gunshot induced tangential fracture of parietal bone), group L (n=6, gunshot induced comminuted fracture of bilateral femora) and group M (n=6, combined group H+L). Gastric intramucosal pH (pHi), plasma endotoxin levels in portal vein, and plasma D lactate levels were measured and blood samples were cultured at different intervals after trauma. The animals were sacrificed at 72 h following trauma and intestinal tissues were harvested for pathological examination and diamine oxidase (DAO) activity measurement. Results. In group M at 72 h, pHi was significantly lower than that of group H and L (P< 0.01), and plasma endotoxin level was significantly higher than that of group H (P< 0.01) and group L (P< 0.05). Simultaneously, in groupM, D lactate level was markedly higher than that of group H (P< 0.01), and incidence of positive blood culture was much higher than that of group H and L (P<0.05). Necrosis and exfoliation were revealed at ileum villus top in all traumagroups, especially in group M, in which ileum DAO activity declined most significantly as well. Conclusion. Multiple trauma is prone to cause gastrointestinal ischemia even without hemorrhagic shock. The damage of gut barrier in multiple trauma appears to be more severe than that in one site trauma, thereby promoting gut derived endotoxemia and bacterial translocation and contributing to the development of endogenous infection.SURGICAL TREATMENT OF MALIGNANTESOPHAGEAL TUMORS IN PUMC HOSPITAL Guo Huiqin,Li Zejian ,Zhang Fan1 ,Zhang Zhiyong,Xu Letian ,Li Weidong2,Wang Xiuqin2and Wu Min2Department of Thoracic Surgery, PUMC Hospital, CAMS &PUMC, Beijing 100730Key words malignant esophageal tumors; early diagnosis; FHIT geneTo study how to prolong the postoperative survival time of the patientswith malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet (FHIT) gene (a tumor suppressor gene) in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2%in esophageal cancer and 20%in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.展开更多
Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underl...Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.展开更多
Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus nig...Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus niger or Penicillium amagasakiense on caecal microbiota and to further illuminate the potential roles of changes in the gut microbiota in regulating the growth performance and meat quality of broiler chickens.Results: A total of 420 one-day-old healthy Arbor Acres broilers were randomly assigned to 4 treatments: the control group,the antibiotic growth promoter(AGP) supplementation group, and the GOD-A and GOD-P(GODs produced by A. niger and P. amagasakiense, respectively) groups. As a result, supplementation with GOD produced by P. amagasakiense could significantly improve the average daily weight gain and average daily feed intake of broilers before 21 days of age by significantly increasing the enzymatic activities of jejunal amylase and those of ileal amylase, chymotrypsin, and lipase in21-day-old broilers and could increase the enzymatic activities of duodenal amylase, jejunal amylase and lipase, and ileal chymotrypsin and lipase in 42-day-old broilers. Meanwhile, compared with AGP treatment, supplementation with GOD produced by P. amagasakiense significantly decreased the L value of 21-day-old broilers and the Δp H and L* value of 42-day-old broilers, while supplementation with GOD produced by A. niger significantly increased the p H24 hvalue of 21-day-old and 42-day-old broilers by reducing plasma malondialdehyde content. By using 16 S r RNA sequencing, we found that the beneficial bacteria and microbiota in broilers were not disturbed but were improved by GOD supplementation compared with ADP treatment, including the genera Eubacterium and Christensenel a and the species uncultured_Eubacterium_sp,Clostridium_asparagiforme, and uncultured_Christensenel a_sp, which were positively related to the improved intestinal digestive enzymatic activities, growth performance, and meat quality of broilers.Conclusion: The altered gut microbiota induced by supplementation with glucose oxidase produced by P. amagasakiense mediate better regulatory effects on the meat quality and growth performance of broilers than that induced by supplementation with glucose oxidase produced by A. niger.展开更多
文摘This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.
基金supported by grants from the National Key R&D Program(2023YFD1301303)National Natural Science Foundation of China(32472950,U21A20249)+1 种基金China Agriculture Research System of MOF and MARA(CARS-35)National Center of Technology Innovation for Pigs,Zhejiang Agricultural Talents,Taishan Industrial Leading Talents Project.
文摘Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.
基金supported by grants from Chr.Hansen A/S,Boege Alle 10-12,2970 Hoersholm,Denmark.
文摘The effects of dietary probiotic supplementation with viable Bacillus subtilis and Bacillus amyloliquefaciens spores on sow performance,immunity,gut functional status and biofilm formation by probiotic bacteria in piglets at weaning were investigated.Ninety-six sows reared in a continuous farrowing system for one full cycle were fed gestation diets during the first 90 d of pregnancy and lactation diets until the end of lactation.The sows were fed a basal diet without probiotics(control;n=48)or a diet supplemented with viable spores(1.1×10^(9)CFU/kg of feed)(probiotic;n=48).At 7 d of age,sucking piglets(n=12/group)were provided prestarter creep feed until weaning at 28 d of age.The piglets in the probiotic group were supplemented with the same probiotic and dosage as their dams.Blood and colostrum collected from sows and ileal tissues collected from piglets on the day of weaning were used for analyses.Probiotics increased the weight of piglets(P=0.077),improved the weaning weight(P=0.039)and increased both the total creep feed consumption(P=0.027)and litter gain(P=0.011).Probiotics also improved the faecal score in the second(P=0.013)week of life.The immunoglobulin G(IgG)concentrations in sow blood at farrowing and the IgM concentrations in piglet blood at weaning were higher in the probiotic group than in the control group(P=0.046).The piglets from the probiotic-treated sows showed a higher IgM concentration in the ileal mucosa(P=0.050)and a lower IgG concentration in the ileal mucosa(P=0.021)compared with the piglets from control sows.The probiotic-treated piglets had a thicker ileal mucosa(P=0.012)due to the presence of longer villi and larger Peyer's patches(P<0.001).B.subtilis and B.amyloliquefaciens were detected in the probiotic-treated piglets but not the control piglets;these bacteria were present in the digesta and villus structures and formed structures resembling biofilms.Overall,Bacillus-based probiotic supplementation improves the health indices of sows and their piglets.
文摘Two studies were conducted to investigate the effect of Bacillus amyloliquefaciens CECr 5940(BA)as a probiotic on growth performance,amino acid digestibility and bacteria population in broiler chickens under a subclinical necrotic enteritis(NE)challenge and/or fed diets with different levels of crude protein(CP).Both studies consisted of a 2×2 factorial arrangement of treatments with 480 Ross 308 mix-sexed broiler chickens.In study 1,treatments included 1)NE challenge(+/),and 2)BA(1.0×106 CFU/g of feed)supplementation(+/-).In study 2,all birds were under NE challenge,and treatments were 1)CP level(Standard/Reduced[2%less than standard])and 2)BA(1.0×106 CFU/g of feed)supplementation(+/-).After inducing NE infection,blood samples were taken on d 16 for uric acid evaluation,and cecal samples were collected for bacterial enumeration.In both studies,ileal digesta was collected on d 35 for nutrient digestibility evaluation.In study 1,the NE challenge reduced body weight gain(BWG),supressed feed conversion ratio(FCR)and serum uric acid levels(P<0.001).Supplementation of BA increased BWG(P<0.001)and reduced FCR(P=0.043)across dietary treatments,regardless of challenge.Bacillus(P=0.030)and Ruminococcus(P=0.029)genomic DNA copy numbers and concentration of butyrate(P=0.017)were higher in birds fed the diets supplemented with BA.In study 2,reduced protein(RCP)diets decreased BWG(P=0.010)and uric acid levels in serum(P<0.001).Supplementation of BA improved BWG(P=0.001)and FCR(P=0.005)and increased Ruminococcus numbers(P=0.018)and butyrate concentration(P=0.033)in the ceca,regardless of dietary CP level.Further,addition of BA reduced Clostridium perfringens numbers only in birds fed with RCP diets(P=0.039).At d 35,BA sup-plemented diets showed higher apparent ileal digestibility of cystine(P=0.013),valine(P=0.020),and lysine(P=0.014).In conclusion,this study suggests positive effects of BA supplementation in broiler diets via modulating gut microflora and improving nutrient uptake.
基金Supported by the National Natural Science Foundation of China, No.30471687
文摘AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.
文摘BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.
文摘Objective. To study the characteristics and pathogenesis of gut barrier damage following multiple firearm injuries in a porcine model. Methods. Twenty four small pigs were divided into 4 groups: control group (n=6, group C), group H (n=6, gunshot induced tangential fracture of parietal bone), group L (n=6, gunshot induced comminuted fracture of bilateral femora) and group M (n=6, combined group H+L). Gastric intramucosal pH (pHi), plasma endotoxin levels in portal vein, and plasma D lactate levels were measured and blood samples were cultured at different intervals after trauma. The animals were sacrificed at 72 h following trauma and intestinal tissues were harvested for pathological examination and diamine oxidase (DAO) activity measurement. Results. In group M at 72 h, pHi was significantly lower than that of group H and L (P< 0.01), and plasma endotoxin level was significantly higher than that of group H (P< 0.01) and group L (P< 0.05). Simultaneously, in groupM, D lactate level was markedly higher than that of group H (P< 0.01), and incidence of positive blood culture was much higher than that of group H and L (P<0.05). Necrosis and exfoliation were revealed at ileum villus top in all traumagroups, especially in group M, in which ileum DAO activity declined most significantly as well. Conclusion. Multiple trauma is prone to cause gastrointestinal ischemia even without hemorrhagic shock. The damage of gut barrier in multiple trauma appears to be more severe than that in one site trauma, thereby promoting gut derived endotoxemia and bacterial translocation and contributing to the development of endogenous infection.SURGICAL TREATMENT OF MALIGNANTESOPHAGEAL TUMORS IN PUMC HOSPITAL Guo Huiqin,Li Zejian ,Zhang Fan1 ,Zhang Zhiyong,Xu Letian ,Li Weidong2,Wang Xiuqin2and Wu Min2Department of Thoracic Surgery, PUMC Hospital, CAMS &PUMC, Beijing 100730Key words malignant esophageal tumors; early diagnosis; FHIT geneTo study how to prolong the postoperative survival time of the patientswith malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet (FHIT) gene (a tumor suppressor gene) in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2%in esophageal cancer and 20%in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.
文摘Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.
基金supported by the National Natural Science Foundation of China (31972529, 31902184)the National Key Research and Development Projects (2017YFD0500500)the China Postdoctoral Science Foundation(2019M653774)。
文摘Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus niger or Penicillium amagasakiense on caecal microbiota and to further illuminate the potential roles of changes in the gut microbiota in regulating the growth performance and meat quality of broiler chickens.Results: A total of 420 one-day-old healthy Arbor Acres broilers were randomly assigned to 4 treatments: the control group,the antibiotic growth promoter(AGP) supplementation group, and the GOD-A and GOD-P(GODs produced by A. niger and P. amagasakiense, respectively) groups. As a result, supplementation with GOD produced by P. amagasakiense could significantly improve the average daily weight gain and average daily feed intake of broilers before 21 days of age by significantly increasing the enzymatic activities of jejunal amylase and those of ileal amylase, chymotrypsin, and lipase in21-day-old broilers and could increase the enzymatic activities of duodenal amylase, jejunal amylase and lipase, and ileal chymotrypsin and lipase in 42-day-old broilers. Meanwhile, compared with AGP treatment, supplementation with GOD produced by P. amagasakiense significantly decreased the L value of 21-day-old broilers and the Δp H and L* value of 42-day-old broilers, while supplementation with GOD produced by A. niger significantly increased the p H24 hvalue of 21-day-old and 42-day-old broilers by reducing plasma malondialdehyde content. By using 16 S r RNA sequencing, we found that the beneficial bacteria and microbiota in broilers were not disturbed but were improved by GOD supplementation compared with ADP treatment, including the genera Eubacterium and Christensenel a and the species uncultured_Eubacterium_sp,Clostridium_asparagiforme, and uncultured_Christensenel a_sp, which were positively related to the improved intestinal digestive enzymatic activities, growth performance, and meat quality of broilers.Conclusion: The altered gut microbiota induced by supplementation with glucose oxidase produced by P. amagasakiense mediate better regulatory effects on the meat quality and growth performance of broilers than that induced by supplementation with glucose oxidase produced by A. niger.
