Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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.

Feeding Bacillus-based probiotics to gestating and lactating sows is an efficient method for improving immunity,gut functional status and biofilm formation by probiotic bacteria in piglets at weaning

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.

Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats

Obesity is associated with gut dysbiosis and metabolic endotoxin.Junshanyinzhen tea extract(JSTE)reduced fat accumulation and body weight in obese mice.However,the effects and mechanism of JSTE in preventing obesity were unclear.Therefore,we used different doses of JSTE(75,150 and 300 mg/(kg·day))to evaluate the effect on high-fat diet(HFD)-induced rats under 8 weeks of intervention.Here,our results showed that JSTE could significantly reduce body weight gain,blood lipid levels and fat accumulation,improve fatty damage in liver tissue(P<0.05).In addition,JSTE increased the expression of intestinal tight junction proteins(P<0.05),relieved metabolic endotoxemia(P<0.05)and chronic low-grade inflammation in HFD rats.Sequencing of fecal samples showed that JSTE could effectively reverse the microbial diversity and the ratio of Firmicutes to Bacteroidetes to normal levels in HFD-fed rats.Desulfovibrioceae and Erysipelotrichaceae,which are positively related to obesity,were decreased by JSTE intervention(P<0.05).while Bifidobacteriaceae,Bacteroidaceae,Akkermansia,and Clostridium,which are negatively related to obesity,were increased.Together,these results suggested that JSTE might effectively prevent obesity by modulating gut microbiota dysbiosis,intestinal barrier dysfunction,metabolic endotoxemia and chronic low-grade infl ammation in HFD-induced rats.

Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

Bacillus amyloliquefaciens CECT 5940 improves performance and gut function in broilers fed different levels of protein and/or under necrotic enteritis challenge

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.

Influences of enteral nutrition combined with probiotics on gut microflora 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.

GUT BARRIER FUNCTION DAMAGE FOLLOWING MULTIPLE FIREARM INJURIES IN A PORCINE MODEL

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.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

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.

适宜运动与过度训练调控肠道功能和肠-脑轴的作用机制

对运动介导肠道与大脑联络的相关文献进行综述,分析适宜运动与过度训练对肠道功能和肠-脑轴之间神经传导及生物信号分子的影响,以揭示其作用机制。发现:肠道与大脑之间关系密切,肠-脑轴之间的双向神经联系和相关生物信号分子是实现肠道与大脑之间对话的媒介。运动可通过调控肠道与大脑之间的神经联系和相关生物分子影响肠-脑轴,介导肠道与大脑的健康及神经、精神疾病的转归。肠道微生物是实现肠-脑轴之间信息沟通的重要参与者,运动对肠道功能与肠-脑轴的调节可通过调控肠道微生态,及其介导的神经传导途径和生物信号分子的变化发挥终端效应,进而影响高级神经功能。不同强度的运动对肠道微生态及肠-脑轴的调节效应差异颇大,适宜运动和过度训练引起的干预结果截然不同。

黑水虻幼虫肠道微生物的功能及组学应用

黑水虻Hemertia illucens幼虫肠道中栖息着许多种类的微生物,这些微生物与宿主之间的相互作用极为复杂,它们可以影响宿主的生长发育、繁殖能力、营养代谢、行为偏好和寿命。此外,它们还可以调节宿主的免疫系统并保护宿主免受病原体的侵害。深入了解微生物与黑水虻的互作机制,有助于优化黑水虻的生长环境,从而实现更高效的人工繁育。相关文章对微生物与黑水虻互作机理进行了总结,但这些研究方法只能提供微生物群落的结构信息,而无法揭示微生物的功能和代谢能力。因此,宏基因组学、宏转录组学、宏蛋白质组学和代谢组学逐渐被应用,这些技术除了提供关于微生物种群的完整分类,还揭示了它们的功能和代谢能力。通过了解肠道菌群的组成和功能,可以有效调整黑水虻的饲料、饲养环境和生长条件,从而提升黑水虻肠道菌群的稳定,提高黑水虻的生产性能和经济效益。

发酵豆粕对白羽肉鸡生长性能、免疫功能的影响

试验旨在研究用发酵豆粕替代肉鸡饲粮中豆粕用量的40%对白羽肉鸡生长性能、免疫功能的影响。试验选取体况一致和体重接近的120只7日龄AA公雏肉仔鸡,随机分为2个处理组,每组6个重复,每个重复10只鸡。对照组饲喂基础饲粮,发酵豆粕组用发酵豆粕替代40%豆粕。试验期为30 d。结果表明:①与对照组相比,发酵豆粕组白羽肉鸡生长性能指标均无显著变化(P>0.05)。②与对照组相比,发酵豆粕显著降低了白羽肉鸡21日龄和37日龄空肠中内毒素(ET)的含量(P<0.05)。综上所述,在本试验条件下,饲粮中用发酵豆粕替代肉鸡饲粮中豆粕用量的40%可降低白羽肉鸡肠道ET水平,从而增强了机体免疫力和抵抗力。

地衣芽孢杆菌在肉鸡养殖中的应用

地衣芽孢杆菌是厌氧型革兰氏阳性细菌,具有耐高温、耐酸、产酶、产抗菌物质等特性,能够改善肉鸡生长性能,提高免疫性能,促进肠道发育和调节肠道菌群,防治鸡坏死性肠炎和球虫病等疾病,具有替代抗生素的潜力。文章综述了地衣芽孢杆菌对肉鸡生长性能、免疫功能、抗氧化性能、肠道发育和微生物组成的影响及其对坏死性肠炎和球虫病的防治作用,并总结了地衣芽孢杆菌的适宜添加量,以期为地衣芽孢杆菌在肉鸡生产中的应用提供参考。

稻螺共作中国圆田螺肠道和底泥微生物群的比较研究

为构建稻螺生态综合种养模式,本研究分析同一生境下不同发育阶段中国圆田螺(Cipangopaludina chinensis)肠道微生物差异,并将其与底泥微生物进行比较研究。实验利用Ion S5^(TM)XL平台对16S rRNA扩增子进行测序,比较研究成年和幼年螺肠道菌群及其功能。结果显示:底泥中微生物多样性显著高于螺肠道菌群,同时幼螺肠道菌群多样性也显著高于成螺。在所有样品中共鉴定出51门243属,其中拟杆菌门(Bacteroidetes,48.95%)、变形杆菌门(Proteobacteria,20.37%)和厚壁菌门(Firmicutes,7.94%)占据主导地位。指示物种分析发现幼螺肠道中苔藓杆菌属(Bryobacter)、互养菌属(Syntrophus)、酸杆菌属(Acidibacter)、硝化螺旋菌属(Nitro-spira)、玫瑰单胞菌属(Roseomonas)5种菌群丰度显著高于成螺,而这些菌群均与蛋白质、氨基酸等能源物质代谢相关,暗示着幼螺时期所需的能源物质更多,消化代谢能力更强。功能预测结果显示螺肠道中的糖代谢、氨基酸代谢、能量代谢、辅助因子和维生素代谢等功能菌群丰度极显著高于底泥,但是成年和幼年中国圆田螺肠道菌群功能未出现差异,表明在肠道与底泥不同生境下菌群所发挥功能具有一定的偏好性,而同一环境中田螺肠道菌群功能较为一致。综上,螺肠道和底泥的微生物丰度不同,但二者微生物群落组成相似,说明田螺肠道微生物组成的变化与同一生态系统中的底泥密切相关;同时田螺在生长发育过程中肠道菌群组成及其功能较为一致,但处于生长快速阶段的幼螺对能源物质的代谢能力强,为此在养殖过程中应给予幼螺充足营养,适当提高饲料中脂肪、蛋白等能源物质的比例,满足田螺快速生长的能量需求。

基于脑-肠-菌轴探讨天枢穴治疗功能性便秘作用机制

功能性便秘(functional constipation,FC)是常见的一种胃肠功能紊乱疾病,该病发病机制复杂,脑-肠-菌轴(BGMA)在其病理生理中的作用逐渐受到关注,脑-肠与肠道菌群交互障碍可通过神经、内分泌、免疫和代谢等途径影响胃肠道运动、感觉、分泌等功能,进而引起排便异常。天枢穴具有疏调肠腑、理气行滞、健脾和胃、调神的功效,为针灸临床治疗FC的要穴。现代研究表明,针灸天枢穴对该病的影响机制可能与调节BGMA有关,包括促进中枢神经系统、肠神经系统结构与功能的正常化,改善肠道微生态失调,调节脑肠肽的分泌以及抑制促肾上腺皮质激素释放因子的过度表达等。该文从BGMA角度探究脑-肠轴、肠道菌群与FC的发病关系,总结探讨天枢穴治疗FC的内在机制,以期为针灸治疗功能性胃肠疾病提供理论依据和临床应用指导。

Changes in the gut microbiota mediate the differential regulatory effects of two glucose oxidases produced by Aspergillus niger and Penicillium amagasakiense on the meat quality and growth performance of broilers

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.

基于高通量测序分析槲皮素对家蚕生长、产丝量及肠道菌群多样性的影响

【目的】基于高通量测序分析槲皮素对家蚕生长、产丝量及肠道菌群多样性的影响,探究槲皮素在家蚕肠道微生态调控中的作用,为功能性蚕丝的高质量生产提供理论依据。【方法】选取240头品种为9芙×7湘的家蚕分为3组,对照组(NC组)喂食普通桑叶,低剂量槲皮素组(LQR组)和高剂量槲皮素组(HQR组)分别喂食含有1.25%(w/w)和5.00%(w/w)槲皮素的桑叶,从五龄眠起(五龄第1 d)开始连续添食6 d,测定家蚕平均生长速率、存活率和蚕茧质量指标,利用高通量测序分析家蚕肠道菌群的组成。【结果】家蚕添食槲皮素后,平均生长速率减缓,存活率降低,HQR组的全茧量、茧层量和茧层率均显著低于NC组(P<0.05,下同)。添食槲皮素可增加家蚕肠道菌群的丰富度和多样性,HQR组和NC组的家蚕肠道菌群物种组成差异显著。在门分类水平上,各组的优势菌门均为变形菌门、蓝细菌门和厚壁菌门;与NC组相比,HQR组变形菌门的相对丰度显著降低。在属分类水平上,各组的优势菌属均为无色杆菌属、甲基杆菌属、norank_f__norank_o__Chloroplast、鞘氨醇单胞菌属和不动杆菌属;与NC组相比,HQR组无色杆菌属的相对丰度显著降低。KEGG信号通路分析结果显示,HQR组肠道菌群注释到全局和概述图及能量代谢通路的比例均显著高于NC组,而注释到氨基酸代谢和膜转运通路的比例均显著低于NC组;COG功能注释分析结果表明,HQR组注释到氨基酸转运和代谢、能量生成和转换及无机离子转运和代谢类别的比例均显著低于NC组,与KEGG信号通路分析结果相符,说明HQR组家蚕需要消耗更多的能量用于维持正常生长,同时蛋白质的生物合成受限制,不利于家蚕的生长和丝蛋白的合成。【结论】在桑叶中添加槲皮素会引起家蚕肠道菌群组成的变化,使变形菌门和无色杆菌属的相对丰度降低,导致家蚕能量代谢提高,氨基酸代谢、能量生成和转换及膜转运等方面能力下降,影响家蚕生长和产丝量。

反刍动物肠道菌群功能及其健康调控策略研究进展

动物消化道中栖息着数量庞大的微生物,肠道微生物在消化代谢及宿主免疫等方面发挥着诸多作用。肠道菌群稳态有赖于各种微生物的复杂作用,其对于维持宿主健康有重要意义,目前对于反刍动物消化道微生物的研究多聚焦于瘤胃微生物,反刍动物肠道微生物的研究较少且还处于较低水平。本文综述了反刍动物肠道菌群的组成及影响因素、潜在的功能以及肠道健康的调控,为反刍动物肠道菌群的研究提供参考。

背俞功能带推法对慢性疲劳综合征大鼠肠道菌群及色氨酸代谢的影响

目的探究背俞功能带推法改善慢性疲劳综合征(chronic fatigue syndrome,CFS)大鼠的症状,以及对其肠道菌群和色氨酸代谢的影响。方法选取SPF级SD大鼠24只,随机分为空白组8只、造模组16只,造模组制备CFS模型21 d,模型制备成功后随机分为模型组和推法组,每组8只。推法干预14 d,做旷场实验及力竭游泳实验等行为学实验后,取大鼠血清、结肠进行酶联免疫吸附法检测血清色氨酸(tryptophan,TRP)、犬尿氨酸(kynurenine,KYN)及结肠吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO),取肠道粪便进行16 s rRNA测序分析肠道菌群结构及多样性。结果与空白组大鼠相比,模型组大鼠总路程、跨格数、中心区时间和路程、进入中心区次数力竭游泳时间均显著减少(P<0.01);与模型组相比,推法组大鼠上述各项指标均增加(P<0.05)。在门水平,与空白组相比,模型组厚壁菌门、拟杆菌门和疣微菌门比例下降,变形菌门和酸杆菌门比例明显上升;与模型组相比,推法组厚壁菌门和酸杆菌门比例下降,而拟杆菌门和变形菌门比例升高。在属水平上,与空白组相比,模型组中罗姆布茨菌属(Romboutsia)和疣微菌科UCG-005菌属(Ruminococcaceae_UCG-005,简称UCG-005)的比例明显降低,而乳杆菌属(Lactobacillus)和双歧杆菌属(Bifidobacterium)比例明显增加;与模型组相比,推法组Lactobacillus和杜氏杆菌属(Dubosiella)比例下降,而Romboutsia和UCG-005比例上升。Alpha和Beta多样性分析,与空白组相比,模型组的菌群丰富度和多样性均降低;与模型组相比,推法组大鼠菌群丰富度和多样性有明显上升;但组间差异均无统计学意义(P>0.05)。LEfSe分析中,与空白组相比,模型组的优势物种主要聚集在目、科、属,推法组的优势物种主要聚集在科、属。与空白组大鼠相比,模型组大鼠血清TRP含量显著降低(P<0.01),血清KYN和结肠IDO含量明显升高(P<0.01);与模型组相比,推法组大鼠血清TRP含量明显升高(P<0.01),血清KYN和结肠IDO含量降低(P<0.05)。相关性分析发现,与TRP相关性较大的菌属包括Lachnospiraceae_NK4A136_group、Lactobacillus、Romboutsia等(P<0.05),与KYN相关性较大的菌属包括Bifidobacterium05、Lachnospiraceae_NK4A136_group、UCG-005(P<0.05或P<0.01),与IDO相关性较大的菌属包括Allobaculum、Lachnospiraceae_NK4A136_group、Romboutsia(P<0.05或P<0.01)。结论背俞功能带推法能明显改善CFS大鼠的疲劳以及焦虑症状,调节菌群代谢物TRP、KYN及结肠IDO含量,对肠道菌群结构及其多样性有一定的调节作用,且部分菌属与TRP、KYN、IDO具有相关性。

不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响——基于肠道菌群和非靶向代谢组学分析

目的研究不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响,探讨肠道菌群及代谢与认知功能之间的相关性。方法采用轮回颠倒的光照周期暴露建立昼夜节律紊乱模型,将模型小鼠分为:安静组(DC)、中等强度持续训练(MICT)运动组(DM)和高强度间歇训练(HIIT)运动组(DH),另设对照组(CC),各组15只,经过6周运动干预后,运用HE染色观察结肠组织、Morris水迷宫检测认知功能、16S rRNA高通量测序检测肠道菌群以及LC-MS检测粪便代谢物。结果①DM组和DH组的腺体破坏程度有所减轻。②DM组和DH组平台潜伏期和初次抵达平台时间显著缩短,游泳距离减少,穿越站台次数和目标象限游泳时间百分比均显著增加。③DC组丰度较高的菌群为柔膜菌门和柔膜菌纲,DM组为瘤胃球菌科,DH组为Lutispora等。④DM组中肌酸、丁酸和甲硫氨酸等代谢物水平显著高于DC组,DH组中花生四烯酸等代谢物水平显著高于DC组。⑤肠道菌群中颤螺菌属、乳酸杆菌属与认知功能相关性显著,代谢物中姜黄素和油酸与认知功能相关性显著。结论MICT和HIIT可调节昼夜节律紊乱小鼠肠道菌群的结构和丰度,改善其认知功能,相关肠道菌群与代谢物参与运动改善昼夜节律紊乱小鼠认知功能的调节。

杀菌类物质对肠道核因子κB通路的调控及免疫毒性研究

杀菌类物质因其杀灭细菌、病毒等微生物特性而被广泛使用。多种杀菌类物质的暴露可能引发人类或动物肠道炎症及免疫系统异常,但相关机理性的研究相对较少。外源性化学物质或病原菌是核因子活化B细胞κ轻链增强子(nuclear factor kappalight-chain-enhancer of activated B cells,简称“NF-κB”)信号通路的重要激动剂,通过激活NF-κB信号通路,调节宿主炎症反应与免疫应答。鉴于此,本文重点梳理探讨了杀菌类物质、NF-κB信号通路、肠道微生物三者之间的相互作用以及它们对宿主潜在的健康影响。结果表明:①NF-κB家族是一组重要的转录因子,几乎存在于所有类型的动物细胞中,参与调控炎症反应、免疫应答、细胞增殖和细胞凋亡等许多生物过程。②肠道微生物中本身的细胞壁成分以及分泌的效应蛋白或代谢产物等是NF-κB信号通路的重要激动剂,这表明肠道微生物与宿主免疫系统之间存在密切联系。肠道微生物对NF-κB信号通路的影响提示了杀菌类物质在肠道免疫调节中可能存在的作用机制。③杀菌类物质可以与肠道微生物之间相互作用进而诱导宿主肠道紊乱,也可以直接作为NF-κB信号通路的激动剂,最终导致宿主肠道免疫系统损伤。开发新型免疫调节剂和抗菌药物,制定治疗肠道免疫相关疾病个性化的预防和治疗策略是未来这一领域的研究方向之一。