曲紅光 楊德慶
膽囊有濃縮和儲存膽汁之作用。膽汁中的膽鹽能刺激腸道的蠕動功能[1],抑制腸道細菌的生長。膽囊切除術后綜合征(PCS)指有過膽囊切除病史的患者術后發生的腹痛、消化不良等腹部癥狀的統稱。與腸道菌群失調息息相關[2-3]。但現在也有部分原因為胃食管反流膽汁反流引起的癥狀。本組研究在探討膽囊切除術后腸道菌群的變化及其與細菌移位的關系,為臨床提供有效防范。
收集新疆維吾爾自治區烏魯木齊市友誼醫院2013 年1 月~12 月治療的147 例膽囊切除患者的完整臨床資料。男86 例,女61 例;年齡47 ~79 歲,平均(56.7 ±5.9)歲;慢性膽囊炎31 例,膽囊結石85 例,膽囊息肉樣病變31 例。本組患者術前均無嚴重全身性疾病。手術方式為開放性膽囊切除術28 例,腹腔鏡膽囊切除術119 例。
對本組患者隨訪至(5 ~12 個月)。結果147 例病例隨訪中,回復144 例,失訪3 例,實際隨訪率97.96%;電話隨訪率為89.48%。
每例患者均于術前3 d 和隨訪就診第一次排便時,各取新鮮糞便0.5g,稀釋后,分別接種至大腸桿菌(E.coli)、腸球菌(Ecc)、葡萄球菌(Sau)、酵母菌(Gjm)、雙歧桿菌(Lgg)、乳桿菌(Lac)等選擇性培養基平板上,按平板活菌計數法計數,對各特征性菌株進行鑒定[4]。
表1 144 例膽囊切除患者腸道細菌計數 比較(±s)

表1 144 例膽囊切除患者腸道細菌計數 比較(±s)
注:與術前比較,aP <0.05,bP <0.01。大腸桿菌(E. coli)、腸球菌(Ecc)、葡萄球菌(Sau)、酵母菌(Gjm)、雙歧桿菌(Lgg )、乳桿菌(Lac)
時間 E. coli Ecc Sau Gjm Lgg Lac Lgg/E.coli術前 7.86 ±1.13 6.96 ±1.21 3.78 ±0.15 3.95 ±1.03 7.8 2 ±0.55 7.58 ±0.47 0.75 ±0.16隨訪時 8.92 ±0.45a 7.55 ±1.43a 3.93 ±0.78 4.24 ±1.15 6.85 ±0.61a 7.08 ±0.46a 0.028 ±0.07 b
本次試驗數據采用SPSS 17.0 軟件進行統計學分析,數據采用均數±標準差表示,計量資料對比采用t 檢驗,以P <0.05 為差異有統計學意義。
對比前后腸道菌群發生明顯變化,表現為E.coli、Ecc 計數較術前顯著增加(P <0.05),而Lgg、Lac 計數則明顯減少(P <0.05)。Lgg/E.coli 比值倒置[5]更為明顯(表1)。說明膽囊切除引起了患者腸道細菌變化[6],導致腸道菌群失調,增加感染發生機會。
人的胃腸道內寄居著種類繁多的微生物,這些微生物稱為腸道菌群[7]。腸道菌群按一定的比例組合,各菌間互相制約,互相依存,在質和量上形成一種生態平衡。其中大腸桿菌恒定存在,厭氧菌如類桿菌屬、雙歧桿菌屬、梭狀芽胞桿菌屬,都有相當數量。正常菌群之間生物的拮抗作用、免疫作用、排毒作用、抗腫瘤作用、抗衰老作用等[8],如果腸內正常菌群占則表示腸內環境相當良好[9-10],(1)吸收水分,糞便較軟,較易排泄。(2)緩和的蠕動,能順利將糞便排出。(3)有助維他命的合成。(4)迅速排出有害物質。(5)避免病原菌的侵害[11]。
正常腸道黏膜菌群主要為雙歧桿菌和乳桿菌,形成固定的菌膜結構和生物屏障,可有效地抵御細菌對機體的侵襲[12-13]。膽囊切除患者膽酸分泌受限,而膽酸經腸內正常菌群脫離,生成石膽酸[14]。有研究結果表明雙歧桿菌、乳酸菌等厭氧菌及含糞真桿菌等需氧菌均具有這種脫離能力,需氧桿菌則無此能力[15-16]。去氧膽酸鹽具有抑制需氧桿菌的作用。顯然膽酸是調節腸內菌群平衡的重要中介環節,腸內厭氧菌等通過促進膽酸的產生從而抑制需氧桿菌的增長繁殖,維持厭氧菌的優勢分布[17]。本研究發現由于Lgg/E.coli 比值出現倒置,腸黏膜菌群中需氧桿菌優勢繁殖,厭氧菌相對減少,致使菌群嚴重紊亂,腸黏膜屏障機能削弱,細菌易位得以發生。加之減少的膽汁不能有效刺激腸道的蠕動功能,抑制腸道細菌的生長,導致腸道菌群失調,使正常的腸道黏膜生物屏障受損,細菌更易侵入出現一系列并發癥如腹瀉、膿血便、黃綠色稀便等。Lgg 數量的減少,而E.coli、Ecc 則明顯增加,其機制未明[18-19]。
腸道膽鹽缺乏是腸道菌群失調原因之一。膽囊切除患者腸道菌群變化膽鹽缺乏是主要致病因素。可適量補充膽鹽,注重推廣腸道菌群的規范化治療、精準化調治。
1 Rosseland AR,Midtvedt T,Aasen AO.Changes in duodenal bacterial flora after cholecystectomy with or without papillotomy in rabbits[J].Scand J Gastroenterol,1984,19(3):304-306.
2 Wang YH,Huang Y.Effect of Lactobacillus acidophilus and Bifidobacterium bifidum supplementation to standard triple therapy on Helicobacter pylori eradication and dynamic changes in intestinal flora[J].World J Microbiol Biotechnol,2014,30(3):847-853.
3 Beliaeva EA,Chervinets VM,Chervinets IuV,et al.The disbiotic changes of intestines microflora in healthy people[J].Klin Lab Diagn,2013,(3):45-47.
4 Leclercq S,Matamoros S,Cani PD,et al.Intestinal permeability,gut-bacterial dysbiosis,and behavioral markers of alcoholdependence severity[J].Proc Natl Acad Sci U S A,2014,111(42):E4485-4493.
5 Kwak DS,Jun DW,Seo JG,et al.Short-term probiotic therapy alleviates small intestinal bacterial overgrowth,but does not improve intestinalpermeability in chronic liver disease [J].Eur J Gastroenterol Hepatol,2014,26(12):1353-1359.
6 Bernard H,Desseyn JL,Bartke N,et al.Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity[J].J Infect Dis,2015,211(1):156-165.
7 Peer X,An G.Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection:an example of agent-based modeling of intestinal bacterial infection[J].J Pharmacokinet Pharmacodyn,2014,41 (5):493-507.
8 Villarreal JM,Becerra-Lobato N,Rebollar-Flores JE,et al.The Salmonella enterica serovar Typhi ltrR-ompR-ompC-ompF genes are involved in resistance to the bile salt sodium deoxycholate and in bacterial transformation [J].Mol Microbiol,2014,92 (5 ):1005-1024.
9 Kaur J,Rana SV,Gupta R,Gupta V,et al.Prolonged orocecal transit time enhances serum bile acids through bacterial overgrowth,contributing factor to gallstone disease[J].J Clin Gastroenterol,2014,48(4):365-369.
10 Gabbard SL,Lacy BE,Levine GM,et al.The impact of alcohol consumption and cholecystectomy on small intestinal bacterial overgrowth[J].Dig Dis Sci,2014,59(3):638-644.
11 Mechetina TA,Il'chenko AA,Lychkova AE.Rifaximin application in the overgrowth bacterial syndrome in the small intestine in patients after cholecystectomy[J].Eksp Klin Gastroenterol,2011 (3):93-100.
12 Pielaciński K,Ejduk A,Wróblewski T,et al.Laparoscopic cholecystectomy for acalculous cholecystitis in a neutropenic patient after chemotherapy for acute lymphoblastic leukemia[J].Wideochir Inne Tech Malo Inwazyjne,2014,9(3):468-472.
13 Gonzalez-Escobedo G,Gunn JS.In Vitro Modeling of Gallbladder-Associated Salmonella spp[J].Colonization.Methods Mol Biol,2015,1225:227-235.
14 Ryu MJ,Jeon TJ,Park JY,et al.A case of gallbladder tuberculosis diagnosed by positive tuberculosis-polymerase chain reaction[J].Korean J Gastroenterol,2014,63(1):51-55.
15 Zhou D,Guan WB,Wang JD,et al.A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa[J].PLoS One,2013,8(7):e70265.
16 Ramery E,Papakonstantinou S,Pinilla M,et al.Bacterial cholangiohepatitis in a dog[J].Can Vet J,2012,53(4):423-425.
17 Toh HS,Chuang YC,Huang CC,et al.Antimicrobial susceptibility profiles of Gram-negative bacilli isolated from patients with hepatobiliary infections in Taiwan:results from the Study for Monitoring Antimicrobial Resistance Trends(SMART),2006-2010[J].Int J Antimicrob Agents,2012,40 Suppl:S18-23.
18 Shukla HS,Tewari M.Discovery of Helicobacter pylori in gallbladder[J].Indian J Gastroenterol,2012,31(2):55-56.
19 Guarino S,Giusti DM,Sorrenti S,et al.Advanced gallbladder cancer misdiagnosis[J].Dig Liver Dis,2012,44(9):798.