替普瑞酮对萎缩性胃炎大鼠胃黏膜p16、TGF-β1表达的影响

背景:慢性萎缩性胃炎(CAG)是一种胃癌癌前状态,预防和阻止其向胃癌进展是一个重要临床问题。目的:观察黏膜保护剂替普瑞酮对CAG发生、发展过程中肿瘤抑制基因p16和转化生长因子-β1(TGF-β1)表达的影响。方法:将健康雄性Wistar大鼠随机分为正常对照组(n=20)、CAG模型组(n=25)和替普瑞酮干预组(n=25),后两组以幽门螺杆菌悬液和乙醇-水杨酸钠溶液灌胃制备CAG模型,替普瑞酮干预组在造模的同时给予替普瑞酮50 mg.kg-1.d-1干预26周。观察各组大鼠胃黏膜大体形态和组织学表现,以免疫组化方法检测胃黏膜p16、TGF-β1表达。结果:正常对照组和替普瑞酮干预组p16蛋白阳性表达率分别为95.0%和73.9%,显著高于CAG模型组的36.4%(P<0.05);TGF-β1蛋白阳性表达率分别为10.0%和30.4%,显著低于CAG模型组的81.8%(P<0.01)。正常对照组与替普瑞酮干预组间p16、TGF-β1蛋白表达差异无统计学意义。与CAG模型组相比,替普瑞酮干预组胃黏膜增厚,腺体数目增多,无出血、糜烂。结论:替普瑞酮能修复胃黏膜损伤,部分逆转胃黏膜萎缩,阻止CAG的发生、发展。其机制可能部分与恢复p16表达和功能以及下调TGF-β1表达有关。     

羔羊胃提取物维B12胶囊对大鼠胃黏膜癌前病变的治疗作用

目的探索羔羊胃提取物维B12(以下简称羔羊胃)胶囊对大鼠胃黏膜癌前病变的治疗作用。方法选取42只Wistar大鼠中的32只(造模组)进行造模实验, 造模组中因灌胃有6只大鼠死亡, 为观察造模结果处死10只, 剩余的16只大鼠随机分为给药组(8只)和非给药组(8只);造模实验结束后, 在未经造模处理的10只大鼠中选取5只作为造模组的正常对照, 其他5只大鼠(阴性对照组)纳入药物干预实验。药物干预方案如下:给药组大鼠每日灌胃0.2 g/kg羔羊胃1次, 非给药组和阴性对照组大鼠均每日灌胃0.2 g/kg 0.9%氯化钠溶液1次, 持续3个月。给药组和非给药组因灌胃各有1只大鼠死亡。评估3组大鼠的体重增量、胃液pH值和胃黏膜的病理改变, 计算胃黏膜表面结节数、胃黏膜癌前病变(上皮内瘤变)评分和发生率, 分析羔羊胃胶囊对大鼠胃黏膜癌前病变的治疗效果。统计学方法采用独立样本t检验、Mann-WhitneyU检验和卡方检验。结果给药组大鼠的第6周体重增量大于非给药组[(508.26±33.96) g比(495.50±23.01) g], 胃液pH值低于非给药组(3.07±0.55比4.45±0.7...     

不同药物干预防治大鼠NSAID相关小肠损伤的观察

目的:通过短期小剂量双氯酚酸口服制备大鼠NSAID相关小肠损伤模型,探讨不同药物干预对大鼠NSAID相关小肠损伤的影响.方法:48只♂ SD大鼠随机分为空白组、实验对照组、药物干预组,其中药物干预组又分为替普瑞酮组、埃索美拉唑组、吉法酯组及甲硝唑组,每组8只.采用双氯芬酸0.78mg/(kg·d),共5 d灌胃制备大鼠小肠损伤模型;替普瑞酮、埃索美拉唑、吉法酯、甲硝唑组分别以15.63、4.17、31.25、156.25 mg/(kg·d),于造模前1 d起灌胃,每天1次,共6 d.实验期间大鼠正常饮食饮水.5 d后处死所有大鼠,观察小肠黏膜的大体及组织学损伤情况.结果:实验对照组大鼠大体评分及组织学评分均较空白组明显升高(4.38±1.41,4.00±1.85 vs 0,均P<0.05);与实验对照组比较,替普瑞酮、埃索美拉唑、吉法酯、甲硝唑组大体评分均明显降低(2.38±1.69、2.00±2.27、1.13±1.36、2.00±1.60 vs 4.38±1.41,均P<0.05),组织学评分除替普瑞酮组外,其余各组均有显著下降(2.25±1.39、1.88±1.25、1.75±0.71、2.00±1.07 vs 4.00±1.85,均P<0.05);各药物干预组间比较,差异无统计学意义(均P>0.05).结论:短期小剂量双氯芬酸口服即可致小肠黏膜损伤,替普瑞酮、埃索美拉唑、吉法酯、甲硝唑对大鼠NSAID相关小肠损伤具有保护作用,可有效减轻大鼠小肠损伤.     

泮托拉唑对应激性胃溃疡大鼠雌激素诱导基因相关肽的影响

采用水浸-束缚（WRS）方法建立大鼠应激性溃疡（SU）模型，将大鼠分为对照组、单纯造模组及造模干预组（应用泮托拉唑干预），观察胃黏膜损伤指数（UI）及组织学变化，采用血气分析测定胃黏膜pHi，RT-PCR方法、免疫组化染色法检测雌激素诱导基因相关肽（TFF1）基因及蛋白表达，分光光度计比色法观察氨基己糖表达。结果模型组与对照组比较，UI升高，phi、氨基己糖、TFF1、TFF1 mRNA均降低（P均〈0.01）；与单纯造模组比较，造模干预组UI降低，pHi、氨基己糖、TFF1、TFF1 mRNA均升高（P均〈0.01）。模型组UI与TFF1呈负相关（P〈0.05）。提示TFF1参与胃黏膜保护，泮托拉唑可能通过上调，TFF1、pHi、氨基己糖参与胃黏膜的防御屏障。     

老龄与非老龄大鼠胃黏膜组织结构的增龄变化

目的 比较Wistar大鼠胃黏膜组织结构的随龄变化. 方法 选择3月龄(体质量200～300 g)及22月龄(体质量600～800 g)清洁级健康Wistar大鼠各6只.光镜下观察老龄、非老龄大鼠胃黏膜腺体厚度、黏膜肌层厚度、固有腺体数量;胃蛋白酶试剂盒生化检测胃黏膜组织胃蛋白酶活力,免疫组化方法检测大鼠黏膜增殖细胞核抗原(PCNA)的表达. 结果 老龄和非老龄大鼠胃黏膜均未见肠上皮化生、不典型增生及肿瘤的发生.老龄组胃黏膜腺体厚度低于非老龄组,分别为(271.5±47.4)μm和(350.9±53.3)μm(t=2.731,P<0.05),老龄组胃黏膜肌层较非老龄组增厚,分别为(98.1±13.1)±μm和(62.4±10.6)μm(t=5.174,P<0.001).胃黏膜组织蛋白酶含量老龄组为(3.011±1.222)U,非老龄组为(4.733±1.304)U,老龄组明显下降(t=2.361,P=0.05).非老龄组大鼠胃黏膜中PCNA阳性细胞主要位于胃腺颈部增殖细胞带,表达规律,细胞核染色阳性;老龄组胃腺颈部增殖细胞带PCNA阳性表达较非老龄组厚度降低,位置下移,偏向于黏膜肌层. 结论 老龄大鼠胃腺体萎缩、黏膜肌层增厚的发生率增加,胃蛋白酶原分泌减少,胃颈腺干细胞的增殖能力下降.     

替普瑞酮对烧伤大鼠胃黏膜热休克蛋白和诱生型一氧化氮合酶表达的影响

替普瑞酮是树木浆液中含有的萜烯衍生物，具有组织修复作用，据文献报道替普瑞酮可诱导产生热休克蛋白(HSP)，以往的研究多集中于其对乙醇、束缚水浸应激、幽门螺杆菌等引起的胃黏膜损害。本研究通过建立烧伤大鼠急性胃黏膜损伤模型，观察替普瑞酮对严重烧伤大鼠胃黏膜HSP60、HSP70和诱生型一氧化氮合酶(iNOS)表达的影响，探讨其保护作用和机制。     

萎胃康对萎缩性胃炎大鼠TFF3和Bcl-2表达的影响

目的以肠三叶因子(TFF3)和B细胞淋巴瘤基因-2(Bcl-2)两种蛋白为切入点,探讨萎胃康治疗慢性萎缩性胃炎(CAG)的可能机制。方法 SD大鼠84只随机分为造模组70只,正常对照组14只。采用复合造模法制备CAG大鼠模型,经6 w造模成功后,将造模组剩余的60只大鼠随机分为模型对照组及萎胃康高、中、低剂量组和阳性药物组(12只/组)。各组给予相应的药物,每天灌胃1次,连续治疗30 d后,分别用Realtime PCR法和Western印迹法检测各组大鼠胃黏膜TFF3和Bcl-2两种蛋白的表达。结果与正常组比较,模型组大鼠胃黏膜TFF3 mRNA表达和Bcl-2蛋白表达均显著升高(P<0.05);与模型组比较,各治疗组大鼠胃黏膜TFF3 mRNA表达和Bcl-2蛋白表达均显著降低(P<0.05);其中以萎胃康高剂量组降低最明显,较萎胃康中、低剂量组有显著差异(P<0.05)。结论抑制胃黏膜TFF3和Bcl-2表达是萎胃康颗粒治疗CAG的机制之一。     

大鼠幽门螺杆菌感染慢性萎缩性胃炎模型的研究

目的 建立Hp相关CAG大鼠模型,探讨Hp与胃粘膜损伤因子在CAG中的致病作用.方法 采用二级、体质量90 g～110 g、♂Wistar大鼠60只,随机分为Hp感染CAG模型组,单纯Hp感染组,单纯胃粘膜损伤CAG模型组与对照组.采用灌胃接种Hp菌株(SSl),30 g/L水杨酸钠灌胃,5 mmol/L去氧胆酸钠溶液、50 mL/L乙醇交替自由饮用及饥饱失常的方法建立Hp相关CAG模型.Hp末次接种12 wk后处死所有动物,检测Hp感染情况及粘膜固有层厚度、粘膜表面上皮层厚度,壁细胞计数和肠化、不典型增生等病变.结果 Hp感染CAG模型组及单纯Hp感染组Hp阳性.Hp感染CAG模型组出现以淋巴细胞浸润为主的慢性炎症,粘膜固有层厚度,胃窦(68±4)/μm,胃体(315±40)μm,粘膜表面上皮层(71±7)μm,PAS阳性层厚度(81±7)μ与正常组(99±16)μm,(407±33)μm,(101±11)μan,(121±14)μm比较明显变薄(P＜0.01),壁细胞计数(34.9±1.1)/腺管明显减少,正常组为(51.1±2.4)/腺管(P＜0.01),无明显肠化及不典型增生.单纯Hp感染组大鼠亦出现较明显的慢性炎症与活动性炎症,粘膜固有层厚度,壁细胞计数与正常组比较无明显变化.结论 Hp感染大鼠CAG模型的病因、病理与人类CAG病变相似,Hp相关CAG大鼠模型获得了初步成功.可作为Hp相关CAG发病机制及药物筛选较合适的动物模型.单纯Hp感染12 wk内无胃粘膜萎缩病变形成.     

怀山药多糖对大鼠胃溃疡的疗效及胃组织碱性成纤维细胞生长因子水平的影响

[目的]观察怀山药多糖对胃溃疡大鼠的治疗作用,研究怀山药多糖对胃溃疡大鼠胃组织碱性成纤维细胞生长因子（bFGF）水平的影响。[方法]将50只大鼠随机分为5组,分别为空白组、模型组、怀山药多糖组、替普瑞酮组和怀山药多糖＋替普瑞酮组。观察并比较各组胃溃疡的愈合情况,取胃组织匀浆检测并比较bFGF水平。[结果]怀山药多糖组的溃疡指数显著低于模型组（P〈0.01）;怀山药多糖组的胃组织bFGF水平显著高于空白组（P〈0.01）和模型组（P〈0.05）。[结论]怀山药多糖具有良好的胃黏膜保护作用,其机制可能与上调胃溃疡大鼠胃组织bFGF水平有关。     

衰老糖尿病(DM)小鼠模型建立的实验研究

目的探讨衰老糖尿病(DM)小鼠模型的建立及探讨糖尿病与老年痴呆症(AD)关系。方法在糖尿病小鼠模型上建立老年痴呆症模型,小鼠70只,分作为对照实验的单纯痴呆症造模组30只和实验的糖尿病(DM)混合造模组40只。单纯痴呆症造模组15只为正常组,15只皮下注射D-半乳糖和亚硝酸钠,每日一次,直至实验结束,共30日(d),建立拟老年痴呆症。衰老糖尿病(DM)(混合造模)组40只,除10只为正常组外,30只造模DM用链佐霉素(STZ)和四氧嘧啶(ALX)腹腔注射4日(d),建立糖尿病模型;12日后开始皮下注射D-半乳糖和亚硝酸钠33d,每日一次,建立拟老年痴呆症;测定造模前,造模后的血糖含量。结果,DM造模组和正常组血糖,造模前、造模后6日、9日血糖,造模组与正常组比较,P>0.05,差异均无统计学意义;造模后18、20、26、46日(痴呆症造模分别为5、7、13、33日)血糖,造模组与正常组分别为15.28±7.32、7.10±0.92(mmol/L);14.22±3.59、6.82±2.99;12.29±2.67、6.45±1.01;12.39±1.19、6.54±0.47(mmol/L),造模与正常两组比较,P<0.01,差异均有统计学意义。混合造模各组脑匀浆Ach E、GSH、丙二醛(MDA)、清除率测定结果,造模组和正常组比较,P>0.05,差异均无统计学意义;单纯造模各组以上GSH、丙二醛(MDA)、清除率指标,P<0.01,差异均有统计学意义。结论混合造模在糖尿病小鼠模型上建立老年痴呆症模型,血糖明显升高;但抗氧化能力降低没有单纯痴呆组明显。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.