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Copper homeostasis and neurodegenerative diseases

Neural Regeneration Research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International Research laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Next-generation probiotic candidates targeting intestinal health in weaned piglets: Both live and heat-killed Akkermansia muciniphila prevent pathological changes induced by enterotoxigenic Escherichia coli in the gut

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animal nutrition 2024年第2期17卷 110-122页

作者： Cong Lan Hua Li Yuqing Shen Yang Liu Aimin Wu Jun He Jingyi Cai Gang Tian Xiangbing Mao Zhiqing Huang Bing Yu Ping Zheng Jie Yu Junqiu Luo Hui Yan Yuheng Luo key laboratory for animal disease-resistance nutrition of Ministry of Education of china Key Laboratory for Animal Disease-Resistance Nutrition and Feed of Ministry of Agriculture of ChinaKey Laboratory of Animal Disease-Resistant Nutrition of Sichuan ProvinceEngineering Research Center of Animal Disease-Resistance Nutrition Biotechnology of Ministry of Education of ChinaAnimal Nutrition InstituteSichuan Agricultural University

The use of next-generation probiotics （NGP） in pigs for combating diseases has been subject to limited *** we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut *** the first screening experiment,we found that the abundance of *** peaked at 14 d old but decreased at weaning （21 d old;P<0.05）,suggesting the weaning period may be an effective window for *** *** that,48 crossbred weaned pigs at 28 d old were randomly assigned to five groups:control （CON）,high/low live *** （HA/LA）,and high/low heatkilled *** （HIA/LIA）.From 1 to 28 d old,the CON group received gastric infusion of anaerobic sterile saline every other day;the HA and LA groups were gavaged every other day with 1×1010CFU/5 m L and 5×10～8CFU/5 mL live ***,respectively;and the HIA and LIA groups were gavaged every other day with 1×1010CFU/5 mL and 5×10～8CFU/5 mL heat-killed ***,*** d 29,pigs in the CON group were randomly and equally divided into two groups,one of which was named the enterotoxigenic Escherichia coli （ETEC） group,and all groups except CON received a 5-d ETEC *** supplementation of *** numerically reduced the diarrhea rate of weaned pigs compared to the pigs that only received the ETEC challenge （P=0.57）,but the LIA group had a higher diarrhea rate than the CON group （P<0.05）.Consistent with this,the supplementation of *** improved the small intestinal morphology and structure,proportion of CD4+T lymphocytes in the blood,as well as the expression of genes related to intestinal barrier and antioxidant indices of pigs with ETEC challenge,especially for the LA group （P<0.05）.Meanwhile,*** supplementation reduced the expression of ETEC virulence factor genes in the ileum and colon of pigs challenged by ETEC （P<0.05）.Therefore,*** may protect the intestinal health of weaned piglets from damage caused by

关键词： Akkermansia muciniphila Weaned piglet Enterotoxigenic Escherichia coli challenge Intestinal health

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Artificial parasin I protein(API)supplementation improves growth performance and intestinal health in weaned piglets challenged with enterotoxigenic Escherichiacoli

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animal nutrition 2024年第3期18卷 154-165页

作者： Congzhi Zou Wanxin Zhao Shenggang Yin Xiaoyu Xiang Jiayong Tang Gang Jia Lianqiang Che Guangmang Liu Xiaoling Chen Gang Tian Jingyi Cai Bo Kang Hua Zhao key laboratory for animal disease-resistance nutrition of Ministry of Education Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Agriculture and Rural AffairsKey Laboratory for Animal Disease-Resistance Nutrition of Sichuan ProvinceAnimal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130China College of animal Science and Technology Sichuan Agricultural UniversityChengdu 611130China

Diarrheas are common risks faced by piglets during the weaning *** study investigated the alleviating effects of artificial parasin I protein(API)on growth performance and intestinal health of weaned pigs upon enterotoxigenic Escherichia coli(ETEC)*** piglets were randomly divided into five groups and fed a basal diet(CON)or basal diet supplemented with API at 0,750,and 1500 mg/kg or antibiotics for 5 *** d 15 and 25,piglets were challenged with ETEC K88 except for the CON *** the ETEC challenge(d 1–14),dietary API supplementation improved growth performance,and 750 mg API increased(P<0.05)the average daily gain(ADG),decreased(P<0.05)feed to gain ratio(F/G)and diarrhea index of weaned *** challenge(during d 15–35)reduced growth performance and increased(P<0.01)the F/G,diarrhea rate,and diarrhea *** event was accompanied by the numerically increased malondialdehyde(MDA)levels in serum and ileum,the decreased(P<0.05)zonula-occludens-1(ZO-1)and interleukin-6(IL-6)in the ileum,and the increased(P=0.04)secretory immunoglobulin A(sIgA)protein in the *** parasin I protein supplementation alleviated the negative impact of *** 750 mg/kg API inclusion elevated(P<0.05)ADG and decreased(P<0.05)F/*** levels of API decreased(P<0.01)the diarrhea rate and diarrhea ***,API inclusion decreased(P<0.01)the crypt depth in the jejunum,elevated(P<0.05)villus height in the duodenum and villus height to crypt depth ratio in the duodenum and ileum,up-regulated(P<0.05)ZO-1 gene,and down-regulated(P<0.05)mucin-2 gene in the jejunum,and 1500 mg/kg API decreased(P<0.01)sIgA level and down-regulated(P<0.05)IL-1βgene in the ***,750 mg/kg API elevated(P<0.01)Bifidobacteria population and acetic acid concentrations in the cecal *** conclusion,API supplementation alleviates the negative impact of ETEC on growth performance and intestinal health,thus can be applied as an antibiotic alternative in weane

关键词： Artificial parasin I protein Growth performance Intestinal barrier Diarrhea Weaned piglet

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The toxicological effect of dietary excess of saccharicterpenin,the extract of camellia seed meal,in piglets

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Journal of Integrative Agriculture 2020年第1期19卷 211-224页

作者： WANG Man YU Bing HE Jun YU Jie LUO Yu-heng LUO Jun-qiu MAO Xiang-bin CHEN Dai-wen key laboratory of animal disease-resistance nutrition Animal Nutrition InstituteSichuan Agricultural University

Recently, saccharicterpenin extracted from Camellia oleifera seed meal has become a widely used feed supplement in animal husbandry. In order to assess its safety, this study was designed to investigate the toxicity and histopathological effects of saccharicterpenin on piglets. One hundred-fifty weaned pigs((Yorkshire×Landrace)×Duroc), 75 males and 75 females with body weight(BW) of(7.35±0.29) kg, were randomly allotted to groups receiving diets supplemented with 0, 500, 1 000, 2 500 or 5 000 mg kg^–1 saccharicterpenin for 70 d. The diet with 500 mg kg^–1 saccharicterpenin supplementation improved liver glutathione peroxidase(GSH-Px) activity, and the diet with 1 000 mg kg^–1 saccharicterpenin supplementation improved liver glutathione S-transferase(GSH-S) activity in piglets on d 70(P<0.05). At 2 500 mg kg^–1, saccharicterpenin in the diets reduced average daily feed intake(ADFI) and average daily gain(ADG) of piglets from d 1 to 35, damaged the cardiac tissue and liver on d 35, and decreased white blood cell counts(WBC), activities of catalase(CAT) and GSH-Px, and concentrations of glucose(GLU) and urea nitrogen(BUN) in the blood of piglets on d 70(P<0.05). In addition, diets with 5 000 mg kg^–1 saccharicterpenin supplementation reduced ADFI, ADG and increased diarrhea rates of piglets from d 36 to 70, and decreased hemoglobin(HGB) concentration and activity of CAT in the blood of piglets on d 70(P<0.05). Moreover, at a rate of 5 000 mg kg^–1, saccharicterpenin supplementation increased pancreas index on d 35 and hepatic index on d 70, and damaged cardiac tissue, liver and spleen during the whole experimental period(P<0.05). These results suggested that dietary 500 mg kg^–1 saccharicterpenin supplementation had beneficial effects on piglets, but excessive supplementation(2 500 or 5 000 mg kg^–1) of saccharicterpenin in the diets could lead to growth retardation, hematological abnormalities and organ injuries.

关键词： growth retardation hematology organ injury piglets saccharicterpenin

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Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets

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Science china(Life Sciences) 2022年第10期65卷 2062-2075页

作者： Wen Ren Bing Yu Jie Yu Ping Zheng Zhiqing Huang Junqiu Luo Xiangbing Mao Jun He Hui Yan Jinlong Wu Daiwen Chen Yuheng Luo key laboratory for animal disease-resistance nutrition of Ministry of Education of china Key Laboratory for Animal Disease-Resistance Nutrition and Feed of Ministry of Agriculture of ChinaKey Laboratory of Animal Disease-resistant Nutrition of Sichuan Provinceand Animal Nutrition InstituteSichuan Agricultural UniversityChengdu61l130China DSM(china)animal nutrition Research Center Co. LtdBazhou 065799China

Growing evidences show a direct link between diarrhea and disorders of gut microbiota in ***,whether there are microbial markers associated with post-weaning diarrhea remains *** the current study,we compared the microbial community,functions and metabolites between healthy weaned piglets(group H,n=7)and piglets with post-weaning diarrhea(group D,n=7),in order to find out diarrhea associated microbial *** of 7 fecal samples was collected from H and D piglets(weaned at 21 d and sampled at 26 d).The metagenomic and untargeted metabolomic analysis revealed that the microbial composition,function and metabolic profile in D pigs was considerably reshaped,including the reduced abundance and number of Bacteroides,which significantly correlated with the diarrhea status of *** carbohydrate metabolism,biosynthesis and metabolism,lipid metabolism,amino acid metabolism,and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H *** significantly changed the metabolic profiles of fecal microbiota,and most of the altered metabolites were negatively or positively correlated with the change in the abundance of *** conclusion,the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets.

关键词： post-weaning piglet diarrhea Bacteroides metabolic dysfunction commensal microbiota

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Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

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Journal of animal Science and Biotechnology 2024年第3期15卷 1173-1189页

作者： Yan Lin Jiangnan Wu Yong Zhuo Bin Feng Zhengfeng Fang Shengyu Xu Jian Li Hua Zhao De Wu Lun Hua Lianqiang Che key laboratory of animal disease‑resistance nutrition Animal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130SichuanChina

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high *** present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR *** Forty multiparous sows were allocated to the control or MET diet groups from mating until *** farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling *** The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of ***,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn *** also increased lactase and sucrase activity in the jejunum of newborn *** addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn *** methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn ***-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell *** contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic *** Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

关键词： Ileum Intrauterine growth restriction Methyl donor Methylation Sows

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Infusion of short chain fatty acids in the ileum improves the carcass traits,meat quality and lipid metabolism of growing pigs

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animal nutrition 2021年第1期7卷 94-100页

作者： Anran Jiao Hui Diao Bing Yu Jun He Jie Yu Ping Zheng Yuheng Luo Junqiu Luo Quyuan Wang Huifen Wang Xiangbing Mao Daiwen Chen Institute of animal nutrition Sichuan Agricultural UniversityKey Laboratory for Animal Disease-Resistance Nutrition of China Ministry of EducationKey Laboratory of Animal Disease-resistant Nutrition and Feed of China Ministry of Agriculture and Rural AffairsKey Laboratory of Animal Disease-resistant Nutrition of Sichuan ProvinceYa'an625014China

Short chain fatty acids(SCFA)are the main products of indigestible carbohydrates undergoing bacterial fermentation in the hindgut,which are related to some physiological *** study was designed to investigate the effects of SCFA infusion by ileum on the carcass traits,meat quality and lipid meta-bolism of growing *** a 28-day study,24 growing barrows fitted with a T-cannula in distal ileum were divided into 4 treatments:1)Control,2)antibiotics(AB),3)AB+300 mL of SCFA1 solution(ABS1),4)AB+300 mL of SCFA2 solution(ABS2).The concentrations of acetate,propionate and butyrate in SCFA1 solution were respectively 61.84,18.62 and 12.55 mmol/L,and in SCFA2 were respectively 40.08,15.41 and 9.78 mmol/L The results showed that the SCFA infusion increased the average daily feed intake and average daily gain of pigs(P<0.05).Meanwhile,the SCFA treatments increased longissimus dorsi area(P<0.05)and carcass weight(P=0.058),decreased the drip loss of longissimus dorsi(P=0.059),and reduced serum concentrations of triglyceride,total cholesterol and urea nitrogen(P<0.05).Besides,the SCFA administration inhibited the mRNA expressions of fatty acid synthase(FAS)and acetyl-CoA carboxylase in longissimus dorsi(P<0.05),the mRNA expression of FAS in the liver(P<0.05),and the mRNA expression of hormone-sensitive lipase in abdominal fat(P<0.05).Short chain fatty acid infusion also enhanced the mRNA expression of carnitine palmitoyltransferase-1αin the liver(P<0.05),the mRNA expressions of peroxisome proliferator activated receptor gamma and lipoprotein lipase in abdominal fat(P<0.05),and the mRNA expressions of free fatty acid receptor 2,glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the colon(P<0.05).These results suggested that SCFA administration in the ileum could improve the carcass traits and meat quality of growing pigs,which was possibly due to the fact that SCFA modulated lipid metabolism.

关键词： Short chain fatty acid Carcass trait Meat quality Lipid metabolism Growing pig

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Effects of low ambient temperatures and dietary vitamin C supplementation on pulmonary vascular remodeling and hypoxic gene expression of 21-d-old broilers

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Journal of Integrative Agriculture 2016年第1期15卷 183-190页

作者： ZENG Qiu-feng YANG Xia ZHENG Ping ZHANG Ke-ying LUO Yu-heng DING Xue-mei BAI Shi-ping WANG Jian-ping XUAN Yue SU Zhuo-wei key laboratory for animal disease resistance nutrition Ministry of EducationInstitute of Animal Nutrition Sichuan Agricultural University

The objective of this study was to evaluate the effects of low ambient temperature （LAT） and dietary vitamin C （VC） sup- plementation on pulmonary vascular remodeling （PVR） and the relative expression of hypoxia inducible factor-la （HIF-la）, vascular endothelial growth factor （VEGF） and its receptor 2 （VEGFR-2） mRNA of lungs in 21-d-old broilers. 400 1-d-old male Cobb broilers were assigned randomly to 4 treatments as follows for 21 d： 1 ） LAT and a basal diet; 2） LAT and a basal diet supplemented with 1 000 mg kg-1 VC （LAT＋VC）; 3） normal ambient temperature （NAT） and a basal diet; 4） NAT and a basal diet supplemented with 1 000 mg kg-1 VC （NAT＋VC）. Each treatment was composed of 10 replicates of 10 birds per replicate. Samples of lung were collected after the broilers were killed at d 21. LAT increased the ratio of vessel wall area to vessel total area （WA/TA, %） and mean media thickness in pulmonary arterioles （mMTPA, %）（P〈0.05）. Dietary VC supplementation decreased mMTPA （P〈0.05）, but had no effect on the WA/TA. LAT increased （P〈0.05） the relative mRNA expression of HIF-la, VEGF and VEGFR-2, while adding VC to the diet could decrease （P〈0.05） their relative mRNA expression. A significant positive correlation existed between the level of VEGF mRNA expression and the value of WA/WT （P〈0.05） or mMTPA （P〈0.05）. These results suggested LAT resulted in pulmonary vascular remodeling, and the increase of HIF-la, VEGF and VEGFR-2 mRNA expression, and dietary VC supplementation can alleviate pulmonary vascular remodeling in broiler by affecting these gene expression.

关键词： broiler hypoxia inducible factor-la low ambient temperature pulmonary vascular remodeling vitamin C

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The effect of dietary tryptophan levels on oxidative stress of liver induced by diquat in weaned piglets

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Journal of animal Science and Biotechnology 2015年第1期6卷 104-110页

作者： Xiangbing Mao Mei Lv Bing Yu Jun He Ping Zheng Jie Yu Quyuan Wang Daiwen Chen animal nutrition Institute Sichuan Agricultural University key laboratory of animal disease-resistance nutrition Ministry of Education

Oxidative stress can induce abnormal tryptophan metabolism. The present study was mainly conducted to determine the effect of dietary tryptophan levels on oxidative stress in the liver of weaned pigs challenged by diquat. A total of 36 PIC piglets weaned at 21 days of age were randomly allotted to 1 of 3 diets containing dietary tryptophan levels of 0.18, 0.30, and 0A5% for 14 d. On day 8, the piglets were injected intraperitoneally with sterile 0.9% NaCI solution or diquat （10 mg/kg body weight）. During the first 7 d of trial, increasing dietary tryptophan levels enhanced average daily gain （P = 0.09） and average daily feed intake （P = 0.08）, and decreased the feed efficiency （P 〈 0.05） of piglets. The growth performance was decreased by diquat injection （P 〈 0.05）. Diquat injection also decreased the activities of the superoxide dismutase （SOD） and glutathione peroxidase （GPx） in the plasma and liver （P 〈 0.05）, increased plasma malondialdehyde （MDA）（P 〈 0.05） and urea nitrogen （P 〈 0.05） concentrations, and enhanced MDA concentration （P = 0.09） and tryptophan 2,3-dioxygenase （TDO） activity （P = 0.07） in liver of piglets. Increasing dietary tryptophan levels could attenuate the effects of diquat injection on the MDA （P = 0.06） concentration and the activities of SOD （P = 0.09） and GPx （P = 0.05） of the liver, and plasma urea nitrogen （P = 0.06） concentration in the piglet. There was a synergistic role for increasing TDO activity in the liver between dietary tryptophan levels and diquat injection （P 〈 0.05）. These results suggest that increasing dietary tryptophan levels could attenuate the oxidative stress of the liver in weaned piglets intraperitoneally injected with diquat via enhancing the antioxidant capacity.

关键词： Antioxidant capacity Diquat Oxidative stress of livers Tryptophan,Weaned piglets

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Yeast-Derived β-1,3-Glucan Substrate Significantly Increased the Diversity of Methanogens During In vitro Fermentation of Porcine Colonic Digesta

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Journal of Integrative Agriculture 2013年第12期12卷 2229-2234页

作者： LUO Yu-heng LI Hua LUO Jun-qiu ZHANG Ke-ying key laboratory for animal disease-resistance nutrition of Sichuan Province and china Ministry of Education/Institute of animal nutrition Sichuan Agricultural University

The β-1,3-glucan from yeast has been extensively examined for its immuno-enhancing effects in ***,investigation on the relationship among β-glucan,gut microbiota and immune-modulating effects remains limited particularly in *** the critical roles of gut methanogens in the microbial fermentation,energy metabolism and disease resistance,we investigated the phylogenetic diversity of methanogens from fermented cultures of porcine colonic digesta with（G） or without（N） yeast β-glucan based on sequences of the archaeal 16S rRNA gene.A total of 145 sequences in the G library were assigned into 8 operational taxonomic units（OTUs） with the majority of sequences（114/145） related to strains Methanobrevibacter millerae or Methanobrevibacter gottschalkii with high identities ranging from 97.9 to 98.6%,followed by 23 sequences to Methanobrevibacter ruminantium,2 sequences to Methanobrevibacter smithii and one sequence to Methanobrevibacter *** 142 sequences in the N library were assigned to 2 OTUs with most sequences（127/142） related to strains *** or *** with sequence identities ranging from 97.9 to 98.5%,and 15 sequences related to *** with 97.9% *** diversity index showed that the G library exhibited significantly higher archaeal diversity（P0.05） and Libshuff analysis indicated the differences in the community structure between the two libraries were significant（P0.0001）.In conclusion,the current study provides evidence that addition of yeast β-glucan significantly increased the diversity of methanogens in in vitro fermented porcine colonic digesta.

关键词： β-glucan methanogen diversity pig colonic digesta in vitro

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