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400042 重庆,陆军特色医学中心消化内科
[陈东风,E-mail: chendf1981@126.com CHEN Dongfeng, E-mail: chendf1981@126.com
收稿:2022-05-12,
修回:2022-05-23,
纸质出版:2022-08-15
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慕之勇, 周银斌, 肖潇, 等. 肝硬化门脉高压症患者胃菌群特征分析[J]. 陆军军医大学学报, 2022,44(15):1576-封3.
Zhiyong MU, Yinbin ZHOU, Xiao XIAO, et al. Characteristics of gastric microbiota in cirrhotic patients with portal hypertension[J]. Journal of Army Medical University, 2022, 44(15): 1576-封3.
慕之勇, 周银斌, 肖潇, 等. 肝硬化门脉高压症患者胃菌群特征分析[J]. 陆军军医大学学报, 2022,44(15):1576-封3. DOI: 10.16016/j.2097-0927.202205060.
Zhiyong MU, Yinbin ZHOU, Xiao XIAO, et al. Characteristics of gastric microbiota in cirrhotic patients with portal hypertension[J]. Journal of Army Medical University, 2022, 44(15): 1576-封3. DOI: 10.16016/j.2097-0927.202205060.
目的
2
分析肝硬化门脉高压症患者胃菌群的结构特征、影响因素及其与临床参数间的相关性。
方法
2
收集2020年11月至2021年11月于陆军特色医学中心消化内科住院接受经颈静脉肝内门体分流术(transjugular intrahepatic portosystemic shunt
TIPS)治疗的肝硬化患者的术前胃黏膜与胃液标本,并采集住院期间相关临床参数。采用16S rRNA分析胃菌群的构成及多样性,运用LEfSe寻找差异菌,冗余分析(redundancy analysis
RDA)识别胃微生物群落结构变化的主要影响因素,Spearman相关分析探讨菌群丰度与临床参数间的相关性。
结果
2
变形菌门(
Proteobacteria
)、放线菌门(
Actinobacteria
)、酸杆菌门(
Acidobacteria
)、绿弯菌门(
Chloroflexi
)等在胃黏膜中富集,而厚壁菌门(
Firmicutes
)、梭菌门(
Fusobacteria
)在胃液中富集。肝硬化门脉高压症患者胃黏膜物种Chao1指数显著高于胃液(
P
<
0.01),两者间Shannon指数差异无统计学意义(
P
>
0.05)。PCoA分析表明,胃黏膜与胃液间群落构成差异有统计学意义(
P
<
0.05)。对肝硬化门脉高压性胃病(portal hypertensive gastropathy,PHG)患者胃菌群分析
显示,消化链球菌属(
Peptostreptococcus
)、二氧化碳噬纤维菌属(
Capnocytophaga
)在PHG患者胃黏膜中富集。肝硬化PHG与non-PHG患者间胃黏膜菌群α多样性与β多样性差异均无统计学意义(
P
>
0.05)。RDA分析表明,门静脉压力梯度(portal pressure gradient,PPG)是影响患者胃黏膜菌群结构变化的主要因素(
r
2
=0.683
P
<
0.001)。哈马达菌属(
Hamadaea
)、艾肯氏菌属(
Eikenella
)丰度与PPG呈正相关性(
r
分别为0.633、0.618;
P
<
0.05)。
结论
2
肝硬化门脉高压症患者胃黏膜与胃液菌群结构存在差异,但两者间物种多样性无差异;肝硬化PHG患者胃黏膜菌群构成有特征性改变。PPG是影响胃黏膜菌群结构变化的主要因素,而胃黏膜哈马达菌属及艾肯氏菌属相对丰度的升高可能与肝硬化门静脉高压相关。
Objective
2
To investigate the structure characteristics
influencing factors and the correlation with clinical parameters of gastric microbiota in cirrhotic patients with portal hypertension.
Methods
2
Preoperative gastric mucosa and gastric juice samples were collected from cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) in our hospital from November 2020 to November 2021
and relevant clinical parameters during hospitalization were also obtained. The composition and diversity of gastric microbiota in the patients were analyzed by 16S rRNA high-throughput sequencing. LEfSe analysis was used to search for different bacteria; Redundancy analysis (RDA) was performed to identify the main factors affecting the gastric microbiota community structure; and Spearman correlation analysis was adopted to explore the correlation between the abundance of gastric microflora and clinical parameters.
Results
2
Proteobacteria
Actinobacteria
Acidobacteria
and
Chloroflexi
were enriched in gastric mucosa
while
Firmicutes
and
Fusobacteria
in gastric juice. The Chao1 index of species in gastric mucosa was significantly higher than that in gastric fluid (
P
<
0
.01)
however
the Shannon index of community between the 2 groups was not different (
P
>
0.05). PCoA analysis showed that there was statistical difference in community composition between gastric mucosa and gastric juice (
P
<
0.05). Further analysis of the gastric microbiota indicated that
Peptostreptococcus
and
Capnocytophaga
were abundant in the gastric mucosa of patients with portal hypertensive gastropathy (PHG)
but the α diversity and β diversity of gastric mucosal flora had no significance between PHG and non-PHG patients (
P
>
0.05). RDA analysis suggested that portal pressure gradient (PPG) was the main factor affecting the community structure of gastric mucosa flora (
r
2
=0.683
P
<
0.001)
and the abundance of
Hamadaea
and
Eikenella
were positively correlated with PPG (
r
=0.633
0.618
respectively;
P
<
0.05).
Conclusion
2
The microflora structure between gastric mucosa and gastric juice is different in cirrhotic patients with portal hypertension
but there is no significant difference in the species diversity. The composition of gastric mucosal flora in patients with PHG has characteristic changes
and PPG plays an important role in the structure of gastric mucosa microbiota. The relatively increased abundance of
Hamadaea
and
Eikenella
in gastric mucosa may be associated with portal hypertension in cirrhosis.
SCHUPPAN D, AFDHAL N H. Liver cirrhosis[J]. Lancet, 2008, 371(9615): 838-851. DOI: 10.1016/s0140-6736(08)60383-9.
BOSCH J, ABRALDES J G, BERZIGOTTI A, et al . The clinical use of HVPG measurements in chronic liver disease[J ] . Nat Rev Gastroenterol Hepatol, 2009, 6(10): 573-582. DOI: 10.1038/nrgastro.2009.149.
GARCIA-TSAO G, ABRALDES J G, BERZIGOTTI A, et al . Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American association for the study of liver diseases[J ] . Hepatology, 2017, 65(1): 310-335. DOI: 10.1002/hep.28906.
D'AMICO G, GARCIA-TSAO G, PAGLIARO L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies[J]. J Hepatol, 2006, 44(1): 217-231. DOI: 10.1016/j.jhep.2005.10.013.
GJEORGJIEVSKI M, CAPPELL M S. Portal hypertensive gastropathy: a systematic review of the pathophysiology, clinical presentation, natural history and therapy[J]. World J Hepatol, 2016, 8(4): 231-262. DOI: 10.4254/wjh.v8.i4.231.
MERLI M, NICOLINI G, ANGELONI S, et al . The natural history of portal hypertensive gastropathy in patients with liver cirrhosis and mild portal hypertension[J ] . Am J Gastroenterol, 2004, 99(10): 1959-1965. DOI: 10.1111/j.1572-0241.2004.40246.x.
PATWARDHAN V R, CARDENAS A. Review article: the management of portal hypertensive gastropathy and gastric antral vascular ectasia in cirrhosis[J]. Aliment Pharmacol Ther, 2014, 40(4): 354-362. DOI: 10.1111/apt.12824.
YI Z Q, ZHANG M L, MA Z Y, et al . Role of the posterior mucosal defense barrier in portal hypertensive gastropathy[J ] . Biomed Pharmacother, 2021, 144: 112258. DOI: 10.1016/j.biopha.2021.112258.
RAJILIC-STOJANOVIC M, FIGUEIREDO C, SMET A, et al . Systematic review: gastric microbiota in health and disease[J ] . Aliment Pharmacol Ther, 2020, 51(6): 582-602. DOI: 10.1111/apt.15650.
GIANNELLA R A, BROITMAN S A, ZAMCHECK N. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro [J ] . Gut, 1972, 13(4): 251-256. DOI: 10.1136/gut.13.4.251..
XU J, XU X, VERSTRAETE W. The bactericidal effect and chemical reactions of acidified nitrite under conditions simulating the stomach[J]. J Appl Microbiol, 2001, 90(4): 523-529. DOI: 10.1046/j.1365-2672.2001.01278.x.
ZHANG S Y, SHI D, LI M R, et al . The relationship between gastric microbiota and gastric disease[J ] . Scand J Gastroenterol, 2019, 54(4): 391-396. DOI: 10.1080/00365521.2019.1591499.
高萍, 张绍刚, 张美艳. 肝硬化患者胃内24 h pH监测结果分析[J]. 临床军医杂志, 2011, 39(6): 1267-1268.
GAO P, ZHANG S G, ZHANG M Y. Analysis of 24h pH monitoring results in the stomach of patients with liver cirrhosis[J]. Clin J Med Off, 2011, 39(6): 1267-1268.
SJÖVALL H. Meaningful or redundant complexity—mechanisms behind cyclic changes in gastroduodenal pH in the fasting state[J]. Acta Physiol (Oxf), 2011, 201(1): 127-131. DOI: 10.1111/j.1748-1716.2010.02155.x.
EDGAR R C. UPARSE: highly accurate OTU sequences from microbial amplicon reads[J]. Nat Methods, 2013, 10(10): 996-998. DOI: 10.1038/nmeth.2604.
STACKEBRANDT E, GOEBEL B M. Taxonomic note: a place for DNA-DNA reassociation and 16S rRNA sequence analysis in the present species definition in bacteriology[J]. Int J Syst Evol Microbiol, 1994, 44(4): 846-849. DOI: 10.1099/00207713-44-4-846.
RÖSSLE M. TIPS: 25 years later[J]. J Hepatol, 2013, 59(5): 1081-1093. DOI: 10.1016/j.jhep.2013.06.014.
MCCORMACK T T, SIMS J, EYRE-BROOK I, et al . Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy?[J ] . Gut, 1985, 26(11): 1226-1232. DOI: 10.1136/gut.26.11.1226.
PERINI R F, CAMARA P R S, FERRAZ J G P. Pathogenesis of portal hypertensive gastropathy: translating basic research into clinical practice[J]. Nat Clin Pract Gastroenterol Hepatol, 2009, 6(3): 150-158. DOI: 10.1038/ncpgasthep1356.
DELGADO S, CABRERA-RUBIO R, MIRA A, et al . Microbiological survey of the human gastric ecosystem using culturing and pyrosequencing methods[J ] . Microb Ecol, 2013, 65(3): 763-772. DOI: 10.1007/s00248-013-0192-5.
OHNO H, SATOH-TAKAYAMA N. Stomach microbiota, Helicobacter pylori, and group 2 innate lymphoid cells[J]. Exp Mol Med, 2020, 52(9): 1377-1382. DOI: 10.1038/s12276-020-00485-8.
LIU X S, SHAO L, LIU X, et al . Alterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancer[J ] . EBioMedicine, 2019, 40: 336-348. DOI: 10.1016/j.ebiom.2018.12.034.
ZHANG X M, LI C, CAO W J, et al . Alterations of gastric microbiota in gastric cancer and precancerous stages[J ] . Front Cell Infect Microbiol, 2021, 11: 559148. DOI: 10.3389/fcimb.2021.559148.
HUNT R H, YAGHOOBI M. The esophageal and gastric microbiome in health and disease[J]. Gastroenterol Clin N Am, 2017, 46(1): 121-141. DOI: 10.1016/j.gtc.2016.09.009.
BASSIS C M, ERB-DOWNWARD J R, DICKSON R P, et al . Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals[J ] . mBio, 2015, 6(2): e00037 . DOI: 10.1128/mBio.00037-15.
SCHULZ C, SCHVTTE K, KOCH N, et al . The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection[J ] . Gut, 2018, 67(2): 216-225. DOI: 10.1136/gutjnl-2016-312904.
LI M, SHAO D, ZHOU J, et al . Microbial diversity and composition in six different gastrointestinal sites among participants undergoing upper gastrointestinal endoscopy in Henan, China[J ] . Microbiol Spectr, 2022, 10(3): e0064521. DOI: 10.1128/spectrum.00645-21.
SUNG J, KIM N, KIM J, et al . Comparison of gastric microbiota between gastric juice and mucosa by next generation sequencing method[J ] . J Cancer Prev, 2016, 21(1): 60-65. DOI: 10.15430/JCP.2016.21.1.60.
SUN Q H, ZHANG J, SHI Y Y, et al . Microbiome changes in the gastric mucosa and gastric juice in different histological stages of Helicobacter pylori-negative gastric cancers[J ] . World J Gastroenterol, 2022, 28(3): 365-380. DOI: 10.3748/wjg.v28.i3.365.
SUNG J, COKER O, CHU E, et al . Gastric microbes associated with gastric inflammation, atroph y and intestinal Metaplasia 1 year after Helicobacter pylori eradication[J ] . Gut, 2020, 69(9): gutjnl-2019. DOI: 10.1136/gutjnl-2019-319826.
WU F, YANG L Y, HAO Y H, et al . Oral and gastric microbiome in relation to gastric intestinal metaplasia[J ] . Int J Cancer, 2022, 150(6): 928-940. DOI: 10.1002/ijc.33848.
SOLÉ C, GUILLY S, DA SILVA K, et al . Alterations in gut microbiome in cirrhosis as assessed by quantitative metagenomics: relationship with acute-on-chronic liver failure and prognosis[J ] . Gastroenterology, 2021, 160(1): 206-218. e13. DOI: 10.1053/j.gastro.2020.08.054.
ZENG J, WANG C T, ZHANG F S, et al . Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial[J ] . Intensive Care Med, 2016, 42(6): 1018-1028. DOI: 10.1007/s00134-016-4303-x.
张民生, 冯燕, 江月萍, 等. 肝硬化非曲张静脉破裂出血与血清促胃液素、胃液酸度及门静脉内径关系探讨[J]. 青岛大学医学院学报, 2001, 37(4): 329-330. DOI: 10.3969/j.issn.1672-4488.2001.04.023.
ZHANG M S, FENG Y, JIANG Y P, et al . A study on relationship of nonvaricos-rupture hemorrhage of cirrhosis with serum gastrin, acidity of gastric juice and the inner diameter of portal vein[J ] . J Qingdao Univ Med Sc i, 2001, 37(4): 329-330. DOI: 10.3969/j.issn.1672-4488.2001.04.023.
SWIDSINSKI A, SYDORA B C, DOERFFEL Y, et al . Viscosity gradient within the mucus layer determines the mucosal barrier function and the spatial organization of the intestinal microbiota[J ] . Inflamm Bowel Dis, 2007, 13(8): 963-970. DOI: 10.1002/ibd.20163.
GODDARD A F, SPILLER R C. The effect of omeprazole on gastric juice viscosity, pH and bacterial counts[J]. Aliment Pharmacol Ther, 1996, 10(1): 105-109. DOI: 10.1111/j.1365-2036.1996.tb00183.x.
APRILE L R O, MENEGHELLI U G, MARTINELLI A L C, et al . Gastric motility in patients with presinusoidal portal hypertension[J ] . Am J Gastroenterol, 2002, 97(12): 3038-3044. DOI: 10.1111/j.1572-0241.2002.07122.x.
FAHMY M E, OSMAN M A, MAHMOUD R A, et al . Measuring of gastric emptying in Egyptian pediatric patients with portal hypertension by using real-time ultrasound[J ] . Saudi J Gastroenterol, 2012, 18(1): 40-43. DOI: 10.4103/1319-3767.91739.
GUNNARSDOTTIR S A, SADIK R, SHEV S, et al . Small intestinal motility disturbances and bacterial overgr owth in patients with liver cirrhosis and portal hypertension[J ] . Am J Gastroenterol, 2003, 98(6): 1362-1370. DOI: 10.1111/j.1572-0241.2003.07475.x.
SHAO Y, JIANG Y C, LI H, et al . Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy[J ] . Exp Ther Med, 2021, 22(3): 953. DOI: 10.3892/etm.2021.10385.
SCHÄFFLER H, HERLEMANN D P R, ALBERTS C, et al . Mucosa-attached bacterial community in Crohn's disease coheres with the clinical disease activity index[J ] . Environ Microbiol Rep, 2016, 8(5): 614-621. DOI:10.1111/1758-2229.12411.
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