儿童迁延性腹泻患者肠道菌群和肠黏膜屏障功能的 变化以及双歧杆菌三联活菌散的干预作用

目的探讨儿童迁延性腹泻患者肠道菌群和肠黏膜屏障功能的变化以及双歧杆菌三联活菌散的干预作用。方法选取儿科就诊迁延性腹泻患儿40例为观察组,予以双歧杆菌三联活菌散1.0g/次,3次/d,溶解于温水中口服,连用8周,检测观察组患儿治疗前后肠道菌群数量及肠黏膜屏障指标的变化。另选择同期在我院体检的正常儿童30例为对照组。结果观察组患儿治疗前双歧杆菌、乳杆菌的数量及B/E比值明显少于对照组,而大肠埃希菌数量明显多于对照组(P0.05)。治疗8周后,观察组患儿双歧杆菌、乳杆菌的数量及B/E比值较治疗前明显上升,大肠埃希菌数量较治疗前明显下降(P0.05);观察组患儿治疗前血清D-乳酸、PCT和DAO水平明显高于对照组(P0.05)。治疗8周后,血清D-乳酸、PCT和DAO水平较治疗前明显下降(P0.05)。结论儿童迁延性腹泻患者存在肠道菌群紊乱,引起肠黏膜屏障功能受损,肠黏膜的通透性异常。双歧杆菌三联活菌散治疗儿童迁延性腹泻患者可纠正肠道菌群紊乱,保护肠黏膜屏障功能,降低其通透性,达到治疗腹泻的目的。     

双歧杆菌三联活菌胶囊对胆囊切除术后腹泻患者肠道菌群及sIgA水平的影响

目的探讨双歧杆菌三联活菌胶囊对胆囊切除术后腹泻患者肠道菌群及sIgA水平的影响。方法选取胆囊切除术后腹泻患者68例,分为观察组和对照组。两组患者均予以低脂饮食和止泻药等常规治疗。观察组患者予以口服双歧杆菌三联活菌胶囊420 mg,3次/d,连用4周。对照组除不口服双歧三联活菌肠溶胶囊外余治疗基本同观察组。观察两组患者治疗前后肠道菌群和sIgA水平的变化,并比较其临床疗效。结果治疗4周后,观察组患者双歧杆菌和乳酸杆菌数量较前明显上升,肠杆菌和肠球菌较前明显减少（P〈0.05）,而对照组治疗前后肠道菌群数量均无明显变化（P〉0.05）;两组患者肠道sIgA水平较前明显上升（P〈0.05或P〈0.01）,且观察组上升值明显大于对照组（P〈0.05）;同时观察组患者临床总有效率明显高于对照组（χ2=5.31,P〈0.05）。结论双歧杆菌三联活菌胶囊治疗胆囊切除术后腹泻的疗效确切,能调节患者肠道菌群失调,从而重建肠道微生态平衡,提高肠道免疫力,改善和保护肠道功能。     

溃疡性结肠炎患者肠道菌群和肠黏膜屏障的变化及益生菌的干预作用

目的探讨溃疡性结肠炎(UC)患者肠道菌群和肠黏膜屏障的变化及益生菌的干预作用。方法选取2014年1月-2017年12月内科门诊就诊活动期UC患者50例为观察组,予以双歧杆菌三联活菌胶囊2粒/次(210mg/粒),饭后30min温水送服,2次/d,连用8周。检测观察组治疗前与治疗后肠道菌群数量及肠黏膜屏障指标的变化。另选择同期肠镜检查未见肠道病变的正常成人30例为对照组。结果观察组患者治疗前双歧杆菌和乳杆菌的数量明显少于对照组,而大肠杆菌数量明显多于对照组(Ps0.05)。治疗8周后,观察组患者双歧杆菌和乳杆菌的数量较治疗前明显上升(Ps0.05),但仍明显低于对照组(Ps0.05);而大肠杆菌数量较前明显下降(Ps0.05),但仍明显高于对照组(Ps0.05)。同时观察组患者治疗前血清ET、D-乳酸和PCT水平明显高于对照组(Ps0.05)。治疗8周后,血清ET、D-乳酸和PCT水平较治疗前明显下降(Ps0.05),但仍明显高于对照组(Ps0.05)。结论双歧杆菌三联活菌胶囊治疗活动性UC能纠正患者肠道菌群紊乱,修复肠黏膜屏障。     

双歧三联活菌胶囊对结直肠癌术后肠道菌群及肠黏膜通透性的影响

目的探讨双歧三联活菌胶囊对结直肠癌术后肠道菌群及肠黏膜通透性的影响。方法选取拟行手术治疗的结直肠癌患者78例,随机分为观察组和对照组。两组患者术前常规禁食、肠道准备,采用开放根治性结/直肠癌切除手术治疗,术后予以围手术期常规治疗,并予以等氮量、等热量的营养支持。观察组术后第3天加用双歧三联活菌胶囊630mg/次,2次/d,连用7d。观察两组患者术前及治疗7d后肠道菌群(双歧杆菌、乳酸杆菌、大肠埃希菌和粪肠球菌)及肠黏膜通透性指标[血清二胺氧化酶(DAO)]的变化,并比较感染并发症的发生率。结果治疗7d后,两组患者双歧杆菌、乳酸杆菌和粪肠球菌数量较前明显下降,大肠埃希菌数量较前明显上升(t=2.17、2.25、2.21、2.32、2.89、3.08、2.97、3.12,P0.05或P0.01),且观察组下降或上升的幅度明显小于对照组(t=2.14、2.25、2.18、2.23,P0.05);两组血清DAO水平均较前明显上升(t=2.27、3.21,P0.05或P0.01),且观察组上升幅度明显小于对照组(t=2.23,P0.05);同时观察组患者感染并发症的总发生率明显低于对照组(χ2=5.03,P0.05)。结论结直肠癌术后存在一定程度的肠道菌群的紊乱,肠黏膜通透性上升和肠道屏障功能受损。双歧三联活菌胶囊用于结直肠癌术后可纠正与调节肠道菌群的紊乱,降低肠黏膜通透性,保护与修复肠黏膜屏障功能,从而减少或避免肠道细菌和内毒素的移位,降低感染并发症的发生。     

双歧杆菌四联活菌片 对重症脑卒中患者肠道功能的影响

目的探讨双歧杆菌四联活菌片对重症脑卒中患者肠道菌群及肠黏膜屏障功能的影响。方法选择重庆市人民医院2017年1月至2017年11月收治的100例重症脑卒中患者,随机将入选患者分为治疗组和对照组各50例。治疗组在常规肠内营养(EN)治疗基础上联用双歧杆菌四联活菌片治疗,对照组给予常规EN治疗。比较两组患者治疗前后营养状况、肠道菌群数量和肠黏膜屏障功能。比较两组患者治疗后消化道并发症发生率。结果治疗前,两组患者营养状况、肠道菌群数量和肠黏膜屏障功能差异无统计学意义(P0.05)。治疗后,两组患者营养状况指标白蛋白(ALB)、血红蛋白(Hb)和三头肌肌围(MAMC)水平,肠道有益菌(双歧杆菌、乳杆菌和拟杆菌)数量均有所上升,肠黏膜屏障功能指标二胺氧化酶(DAO)、D-乳酸水平及肠道有害菌数量(小梭菌和肠球菌)均降低。与对照组相比,治疗组患者ALB、Hb和MAMC水平,肠道双歧杆菌、乳杆菌和拟杆菌数量均显著升高,DAO、D-乳酸水平和小梭菌、肠球菌数量均显著降低,差异有统计学意义(P0.05)。治疗组患者消化道并发症发生率均低于对照组(P0.05)。结论双歧杆菌四联活菌片能够显著改善脑卒中患者的营养状况,有效调节菌群失衡,改善肠黏膜屏障功能,降低并发症发生。     

术前补充益生菌对肠道手术患者术后肠道菌群 及肠黏膜屏障功能的影响

目的探讨术前补充益生菌对肠道手术患者术后肠道菌群及肠黏膜屏障功能的影响。方法选取肠道手术患者86例,随机分为观察组和对照组各43例。两组患者术前予以常规肠道准备,术后给予等营养支持及抗生素等治疗。观察组患者术前7 d开始加用双歧杆菌三联活菌胶囊温水口服,630 mg/次,2次/d。观察两组患者术后肠道功能恢复及感染并发症情况,并比较术前7 d及术后首次自然排便时两组患者肠道菌群数量及肠黏膜屏障指标变化。结果观察组患者术后肠鸣音恢复时间、肛门排气时间、排便时间均短于对照组(均P0.05),术后感染并发症的发生率低于对照组(P0.05)。术后首次自然排便时两组患者肠道双歧杆菌、乳杆菌数量及B/E值显著低于术前7 d时,大肠埃希菌数量高于术前7 d时(均P0.05),且观察组患者术后双歧杆菌、乳杆菌数量及B/E值均高于对照组,大肠埃希菌数量明显少于对照组(P0.05)。术后首次自然排便时两组患者血清D-乳酸和DAO水平高于术前7 d时(P0.05),且观察组患者术后D-乳酸和DAO水平低于对照组(P0.05)。结论肠道手术患者术前补充益生菌可调节肠道菌群,降低肠黏膜通透性,改善其肠道功能,减少术后感染并发症的发生率。     

双歧三联活菌胶囊对胆囊切除术后腹泻患者血清D-乳酸及肠道菌群的影响

目的探讨双歧三联活菌胶囊对胆囊切除术后腹泻(PCD)患者血清D-乳酸及肠道菌群的影响。方法选取80例PCD患者,随机分为观察组(n=40)和对照组(n=40)。两组均予以低脂饮食和止泻药等常规治疗。观察组加用双歧三联活菌胶囊420mg/次,3次/d,连用6周,温开水或温牛奶送服。检测两组治疗前后血清D-乳酸水平及肠道菌群数量变化,并比较其临床疗效及不良反应。结果观察组与对照组分别失访2例(5.0%)和4例(10.0%),两组失访率比较差异无统计学意义(P0.05)。治疗6周后,两组血清D-乳酸指标较治疗前均明显下降(对照组治疗前后比较,P0.05;观察组治疗前后比较,P0.01),观察组下降幅度较对照组更明显(P0.05);同时观察组双歧杆菌和乳酸杆菌数量增加,肠杆菌和肠球菌数量下降(P0.05),而对照组肠道菌群数量变化差异无统计学意义(P0.05);同时观察组其总有效率(92.11%)较对照组(72.22%)高(χ2=5.05,P0.05)。结论双歧三联活菌胶囊治疗PCD具有确切疗效,能降低血清D-乳酸指标,纠正并调节患者肠道微生态紊乱,重建肠道微生态平衡,改善其肠道功能。     

双歧三联活菌胶囊联合美沙拉嗪对 溃疡性结肠炎患者肠道微生态影响

目的探讨双歧三联活菌胶囊联合美沙拉嗪肠溶片对溃疡性结肠炎(ulcerative colitis,UC)患者肠道微生态的影响。方法选取2015年1月至2017年4月我院内科门诊治疗的活动期轻中度UC患者78例,随机分为观察组和对照组。两组均给予口服美沙拉嗪肠溶片1.0 g/次,4次/d。观察组在此基础上加以双歧三联活菌胶囊420 mg/次,3次/d,口服,两组均连用8周。比较两组治疗前后肠道菌群中乳杆菌、双歧杆菌、大肠埃希菌数量的变化和双歧杆菌(B)与大肠埃希菌(E)的比值变化,并评估两组治疗后临床效果。结果治疗前两组乳杆菌、双歧杆菌与大肠埃希菌及B/E比值比较,差异无统计学意义(P0.05)。治疗8周后,两组双歧杆菌、乳杆菌数量及B/E比值明显上升(P0.01),大肠埃希菌数量下降(P0.05),但观察组变化幅度更大(P0.05),且总有效率较对照组更高(χ2=4.13,P0.05)。结论双歧三联活菌胶囊联合美沙拉嗪肠溶片可治疗UC,能调节肠道菌群紊乱,重建肠道微生态平衡。     

曲美布汀联合双歧杆菌三联活菌胶囊对功能性消化不良重叠IBS-D患者肠道的影响

目的探讨曲美布汀联合双歧杆菌三联活菌胶囊对功能性消化不良(FD)重叠腹泻型肠易激综合征(IBS-D)患者肠道微生态的影响。方法选取90例FD重叠IBS-D患者,随机分为观察组和对照组各45例。两组患者均予以曲美布汀片100mg/次,3次/d,口服;观察组在对照组基础上加用双歧杆菌三联活菌胶囊630mg/次,2次/d,餐后约30min温水服用,两组患者均连用8周。观察两组患者治疗前后肠道菌群的变化,并比较其临床效果及不良反应。结果治疗8周后,观察组患者粪便中双歧杆菌和乳杆菌数量增加,而肠杆菌、肠球菌和酵母菌数量下降(P<0.05)。对照组患者粪便中这5种菌的数量治疗前后无明显变化(P>0.05)。治疗8周后,观察组患者总有效率高于对照组(χ~2=4.05,P<0.05)。观察组和对照组患者治疗中分别出现不良反应6例(13.33%)和8例(17.78%),症状均较轻微,两组比较差异无统计学意义(χ~2=0.34,P>0.05)。结论曲美布汀联合双歧杆菌三联活菌胶囊治疗FD重叠IBS-D患者疗效较肯定,安全性较高,其作用机制可能是通过调节肠道菌群,重建肠道微生态平衡,从而改善其消化不良及腹泻症状。     

马来酸曲美布汀联合双歧三联活菌胶囊对糖尿病性腹泻患者肠道菌群的影响及疗效观察

目的探讨马来酸曲美布汀联合双歧三联活菌胶囊对糖尿病性腹泻(DD)患者肠道菌群的影响及疗效。方法将86例DD患者随机分为观察组和对照组。两组患者均予以饮食调整、控制血糖和胃肠解痉药等基础治疗。观察组予以双歧三联活菌胶囊(420mg,3次/d,温开水送服)联合马来酸曲美布汀(200mg,3次/d,口服)治疗,对照组予以单用的双歧三联活菌胶囊治疗,两组患者均连用8周。观察并比较两组患者治疗前后肠道菌群数量的变化,比较其临床疗效及药物不良反应。结果治疗8周后,两组患者双歧杆菌、乳酸杆菌数量均较前增加,肠杆菌、肠球菌和酵母菌数量较前减少(P0.05),且观察组变化更明显(P0.05);同时观察组患者临床总有效率(94.74%)较对照组(78.95%)更佳(χ2=4.15,P0.05)。观察组患者治疗中发生不良反应3例,对照组发生1例,症状较轻,两组比较差异无统计学意义(χ2=0.26,P0.05)。结论双歧三联活菌胶囊联合马来酸曲美布汀治疗DD的疗效确切,安全性较佳,能有效缓解其腹泻症状,作用机制与其能纠正肠道菌群紊乱密切相关。     

Interaction of vasoactive intestinal peptide with rat small intestinal epithelial cells after intestinal resection

Specific binding of vasoactive intestinal peptide (VIP) and VIP-stimulated c y c l i c AMP accumulation were studied in small intestinal epithelial cells (both of crypt and villous levels) 3, 7 and 14 d after a 60% resection of the small intestine . The affinity, but not the binding capacity, of VIP receptors decreased during the adaptive hyperplastic response. Basal cyclic AMP levels were similar in cells of both control and resected rats. Resection induced a decrease of potency, but not of efficiency, of VIP on the stimulation of cyclic AMP accumulation.     

肠道微生物对肠道屏障功能完整性的维护机制研究概况

肠道微生物群是一个稳定且复杂的生态系统,可以通过形成菌膜屏障或促进肠道上皮细胞增殖分化等方式形成保护屏障,并在肠道病原菌感染和威胁期间维持和促进免疫稳态中起积极作用。本文重点叙述宿主-肠道微生物相互作用过程中抗病原菌感染的方式,以及肠道微生物参与合成抗菌化合物抵御肠道病原菌入侵和威胁的机制,为调控肠道微生物解决临床胃肠道疾病及其相关症状提供理论参考依据。     

Relationship between intestinal microecology and the translocation of intestinal bacteria

It is now well known that endogenous bacteria can translocate from the intestinal tract and cause many of the complicating infections seen in severely ill, hospitalized patients. Of the hundreds of bacterial species in the intestinal tract, relatively few aerobic/facultative species appear to translocate with any frequency. Van der Waaij and colleagues (1971, 1972a, 1972b) originally proposed that, by a process termed colonization resistance, strictly anaerobic bacteria prevented the intestinal overgrowth and subsequent translocation of these potentially pathogenic aerobic/facultative bacteria. Selective antimicrobial decontamination, designed to maintain colonization resistance, has been effective in reducing the incidence of infectious morbidity in high risk patients. However, the mechanisms controlling bacterial translocation remain unclear, but appear to depend on host factors, as well as on factors inherent in the microbe itself. There is both clinical and experimental evidence supporting the concept that strictly anaerobic bacteria do not readily translocate. Bacteria that are able to survive within macrophages (e.g., Salmonella species and Listeria monocytogenes) translocate easier than others, and there is recent experimental evidence that normal intestinal bacteria may translocate to the draining mesenteric lymph node within host phagocytes. There is also evidence that anaerobic bacteria translocate along with facultative species in situations associated with intestinal epithelial damage, i.e., burn trauma, oral ricinoleic acid, and acute mesenteric ischemia. In contrast, recent experimental evidence demonstrates that facultative bacteria can translocate across a histologically intact intestinal epithelium, and that the ileal absorptive cell may be at least one portal of entry prior to transport into deeper tissues. It is anticipated that further clarification of the routes and mechanisms involved in bacterial translocation will provide new insights into the treatment and prevention of a significant proportion of the infectious morbidity seen in severely ill, hospitalized patients. Antoni van Leeuwenhoek Lecture presented at the Annual Meeting of the Netherlands Society of Microbiology, Utrecht, 23 November, 1989.     

Effect of intestinal ischaemia on intestinal VIP levels and VIP interaction with intestinal epithelial cells from rat

1. The number (but not the affinity) of vasoactive intestinal peptide (VIP) receptors in small intestinal epithelial cells decreased following intestinal ischaemia in rats as compared to sham-operated animals. 2. There was a parallel decrease of the efficiency (but not the potency) of the neuropeptide upon cyclic AMP formation at the same level after intestinal ischaemia. 3. The surgical manipulation did not modify the level of VIP immunoreactivity in the gut segment studied. 4. These results suggest that the VIPergic system is not directly involved in the high loss of water and electrolytes that appears following intestinal ischaemia.     

Transfer of locally synthesized cholesterol from intestinal wall to intestinal lymph

The cholesterol-fed rat subjected to cannulation of the intestinal lymph duct and injected with acetate-2-(14)C has been utilized for a study of the mechanism by which cholesterol synthesized in the intestinal wall gains access to the circulation. It has been concluded that locally synthesized cholesterol is excreted bidirectionally, approximately half going into the lymph and half into the lumen. Furthermore, under the conditions of these experiments, little of the luminal cholesterol appears to be reabsorbed, which suggests that direct transfer from wall to lymph is the principal route for the entry of this endogenously derived cholesterol pool into the lymph and ultimately into the blood stream. Finally, it has been demonstrated that bile is required for this transfer of cholesterol from wall to lymph as well as for the absorption of dietary cholesterol.     

小鼠肠道优势菌群失衡肠黏液sIgA、黏液素的变化

目的研究肠道菌群失衡对小鼠肠黏膜机械屏障的影响,探讨优势菌群与肠道黏膜屏障的相互作用机制。方法利用ELISA法检测肠黏膜sIgA含量变化,RT-PCR技术及免疫组化法检测肠黏膜上皮细胞Mucin2、Mucin3和防御素mRNA转录产物的变化。结果菌群失衡小鼠小肠段肠黏膜sIgA水平下降,重度菌群失衡组与正常组比较下降显著（P〈0.05）,与轻度菌群失衡组相比下降明显。菌群失衡小鼠上皮细胞中的Mucin2、Mucin3和防御素mRNA转录产物与正常小鼠相比明显增高,在杯状细胞胞浆内Mucin2蛋白阳性表达增强,且重度菌群失衡组与轻度菌群失衡组小鼠比较,Mucin2、Mucin3和防御素增高明显。结论菌群失衡可导致肠黏膜sIgA分泌量随菌群失衡程度呈下降趋势,同时引起黏液层中黏液素和防御素分泌量增加。