Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study

HAN Ziying; SONG Kai; FAN Zhengyang; SONG Xiao; HU Xiaomin; WU Dong

doi:10.12290/xhyxzz.2022-0255

Volume 13 Issue 5

Sep. 2022

Turn off MathJax

Article Contents

Abstract

References

Medical Journal of Peking Union Medical College Hospital > 2022 > 13(5): 800-811. > DOI: 10.12290/xhyxzz.2022-0255

HAN Ziying, SONG Kai, FAN Zhengyang, SONG Xiao, HU Xiaomin, WU Dong. Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(5): 800-811. DOI: 10.12290/xhyxzz.2022-0255

Citation:

PDF (8274 KB)

Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study

HAN Ziying¹,
SONG Kai¹,
FAN Zhengyang¹,
SONG Xiao²,
HU Xiaomin^{3, 4, ,},
WU Dong^{1, 4, ,}

1.
Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
3.
Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
4.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funds:

National Natural Science Foundation of China 32170788

Beijing Natural Science Foundation 7202152

National High Level Hospital Clinical Research Funding 2022-PUMCH-A-026

More Information

Corresponding author:
HU Xiaomin, E-mail: huxiaomin2015@163.com

WU Dong, E-mail: wudong@pumch.cn
Received Date: May 05, 2022
Accepted Date: July 27, 2022
Issue Publish Date: September 29, 2022

Graphical Abstract

Abstract

Abstract

Objective To investigate the gut microbiome composition and changes and its association with disease severity in patients with acute pancreatitis (AP).
Methods This study was a prospective cross-sectional analysis. The subjects of the study were AP patients in Peking Union Medical College Hospital from June 2018 to January 2022 and healthy volunteers. The clinical data and stool samples of the two groups were collected, the 16S rRNA of the gut microbiome was DNA sequenced, and bioinformatic analysis was performed. The differences in gut microbiome between the two groups were compared, and the correlation between the intestinal flora and the severity of AP was analyzed by receiver operating characteristic(ROC) curve.
Results A total of 60 AP patients and 20 healthy volunteers were enrolled. Among the AP patients, 20 were mild AP, 20 were moderately severe AP, and 20 were severe AP. During hospitalization, 22 cases were transferred to ICU, while 38 cases were not. In α diversity analysis, the Shannon index of AP patients was significant decreased compared to healthy volunteers (P < 0.05). β diversity of the two groups was significantly different. At the phylum, family, genus and species levels, there were also significant differences in the microbiome composition between the two groups. Linear discriminant analysis effect size analysis revealed that g_Escherichia-Shigella, g_Enterococcus, and f_Enterococcaceae were dominant in AP patients while g_Blautia, and g_Bifidobacterium were dominant in healthy volunteers. Function analysis found that multiple amino acid biosynthesis pathways were blocked in gut microbiome of AP patients, and potential pathogenicity and migration ability of gut microbiome increased significantly. In subgroup analysis, g_Enterococcus was increased and g_Bacteroidaceae was decreased in ICU patients compared to non-ICU patients. Based on the probability of disease index, the ROC curve showed that the area under the curve for identifying AP patients and AP patients transferred to ICU were 0.996 and 0.743.
Conclusions The pathogenic bacteria increased and the beneficial bacteria decreased in the gut microbiome of AP patients. Changes in gut microbiota are related to the severity of AP disease and therefore have the potential to be used as novel biomarkers for AP.
- acute pancreatitis,
- gut microbiome,
- biomarker,
- functional prediction

FullText(HTML)

References (38)

References

[1]	Iannuzzi JP, King JA, Leong JH, et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis[J]. Gastroenterology, 2022, 162: 122-134. DOI: 10.1053/j.gastro.2021.09.043
[2]	Portelli M, Jones CD. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management[J]. Hepatobiliary Pancreat Dis Int, 2017, 16: 155-159. DOI: 10.1016/S1499-3872(16)60163-7
[3]	Lee PJ, Papachristou GI. New insights into acute pancreatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16: 479-496. DOI: 10.1038/s41575-019-0158-2
[4]	Mederos MA, Reber HA, Girgis MD. Acute Pancreatitis: A Review[J]. JAMA, 2021, 325: 382-390. DOI: 10.1001/jama.2020.20317
[5]	Yu S, Xiong Y, Fu Y, et al. Shotgun metagenomics reveals significant gut microbiome features in different grades of acute pancreatitis[J]. Microb Pathog, 2021, 154: 104849. DOI: 10.1016/j.micpath.2021.104849
[6]	Yu S, Xiong Y, Xu J, et al. Identification of Dysfunctional Gut Microbiota Through Rectal Swab in Patients with Different Severity of Acute Pancreatitis[J]. Dig Dis Sci, 2020, 65: 3223-3237. DOI: 10.1007/s10620-020-06061-4
[7]	Zhu Y, He C, Li X, et al. Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice[J]. J Gastroenterol, 2019, 54: 347-358. DOI: 10.1007/s00535-018-1529-0
[8]	Li XY, He C, Zhu Y, et al. Role of gut microbiota on intestinal barrier function in acute pancreatitis[J]. World J Gastroenterol, 2020, 26: 2187-2193. DOI: 10.3748/wjg.v26.i18.2187
[9]	龚亮, 宋晓, 苏磊, 等. 急性胰腺炎肠道微生态的研究进展[J]. 中华临床营养杂志, 2021, 29: 308-314. DOI: 10.3760/cma.j.cn115822-20210901-00171 Gong L, Song X, Su L, et al. The research progress on gut microbiota in acute pancreatitis[J]. Zhonghua Linchuang Yingyang Zazhi, 2021, 29: 308-314. DOI: 10.3760/cma.j.cn115822-20210901-00171
[10]	中华医学会消化病学分会胰腺疾病学组, 《中华胰腺病杂志》编委会, 《中华消化杂志》编委会. 中国急性胰腺炎诊治指南(2019年, 沈阳)[J]. 中华消化杂志, 2019, 39: 721-730. DOI: 10.3760/cma.j.issn.0254-1432.2019.11.001 Pancreas Study Group, Chinese Society of Gastroenterology, Chinese Medical Association, Editorial Board of Chinese Journal of Pancreatology, Editorial Board of Chinese Journal of Digestion. Chinese guidelines for the management of acute pancreatitis(Shenyang, 2019)[J]. Zhongguo Xiaohua Zazhi, 2019, 39: 721-730. DOI: 10.3760/cma.j.issn.0254-1432.2019.11.001
[11]	王佩, 马良坤, 刘俊涛. 早/中孕期孕妇肠道菌群差异及其与妊娠期糖尿病的关系: 前瞻性队列研究[J]. 协和医学杂志, 2021, 12: 721-728. DOI: 10.12290/xhyxzz.20200122 Wang P, Ma LK, Liu JT, et al. Difference in Gut Microbiota between the First and the Second Trimester of Pregnancy and the Association of Gut Microbiota with Gestational Diabetes Mellitus: A Prospective Cohort Study. [J]. Xiehe Yixe Zahi, 2021, 12: 721-728. DOI: 10.12290/xhyxzz.20200122
[12]	Bozzi Cionci N, Baffoni L, Gaggia F, et al. Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases[J]. Nutrients, 2018, 10: 1723. DOI: 10.3390/nu10111723
[13]	Tan C, Ling Z, Huang Y, et al. Dysbiosis of Intestinal Microbiota Associated With Inflammation Involved in the Progression of Acute Pancreatitis[J]. Pancreas, 2015, 44: 868-875. DOI: 10.1097/MPA.0000000000000355
[14]	Chen J, Huang C, Wang J, et al. Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats[J]. PLoS One, 2017, 12: e0176583. DOI: 10.1371/journal.pone.0176583
[15]	Zhang XM, Zhang ZY, Zhang CH, et al. Intestinal Microbial Community Differs between Acute Pancreatitis Patients and Healthy Volunteers[J]. Biomed Environ Sci, 2018, 31: 81-86.
[16]	Mei QX, Hu JH, Huang ZH, et al. Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis[J]. Acta Pharmacol Sin, 2021, 42: 942-953. DOI: 10.1038/s41401-020-00581-5
[17]	Akshintala VS, Talukdar R, Singh VK, et al. The Gut Microbiome in Pancreatic Disease[J]. Clin Gastroenterol Hepatol, 2019, 17: 290-295. DOI: 10.1016/j.cgh.2018.08.045
[18]	Li Q, Wang C, Tang C, et al. Bacteremia in patients with acute pancreatitis as revealed by 16S ribosomal RNA gene-based techniques [J]. Crit Care Med, 2013, 41: 1938-1950. DOI: 10.1097/CCM.0b013e31828a3dba
[19]	Schmidt PN, Roug S, Hansen EF, et al. Spectrum of microorganisms in infected walled-off pancreatic necrosis- impact on organ failure and mortality[J]. Pancreatology, 2014, 14: 444-449. DOI: 10.1016/j.pan.2014.09.001
[20]	Kim SG, Becattini S, Moody TU, et al. Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus[J]. Nature, 2019, 572: 665-669. DOI: 10.1038/s41586-019-1501-z
[21]	Liu X, Mao B, Gu J, et al. Blautia-a new functional genus with potential probiotic properties? [J]. Gut Microbes, 2021, 13: 1-21.
[22]	中华预防医学会微生态学分会. 中国消化道微生态调节剂临床应用专家共识(2016版)[J]. 中华消化杂志, 2016, 36: 793-804. DOI: 10.3760/cma.j.issn.0254-1432.2016.12.001 Chinese Society of Microecology, Chinese Preventive Medicine Association. Chinese expert consensus on clinical application of microecological agent in digestive tract(2016 version)[J]. Zhonghua Xiaohua Zazhi, 2016, 36: 793-804. DOI: 10.3760/cma.j.issn.0254-1432.2016.12.001
[23]	Van den Berg F, Van Dalen D, Hyoju SK, et al. Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate[J]. Gut, 2021, 70: 915-927. DOI: 10.1136/gutjnl-2019-320430
[24]	Sugahara H, Odamaki T, Fukuda S, et al. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community[J]. Sci Rep, 2015, 5: 13548. DOI: 10.1038/srep13548
[25]	陈国榕, 吴东. 肠道菌群代谢产物丁酸减轻重症急性胰腺炎相关肺损伤的机制[J]. 中华临床营养杂志, 2020, 28: 363-367. DOI: 10.3760/cma.j.cn115822-20201227-00283 Chen GR, Wu D. Mechanism of the intestinal microbial metabolite butyrate in attenuating severe acute pancreatitis associated lung injury[J]. Zhonghua Linchuang Yingyang Zazhi, 2020, 28: 363-367. DOI: 10.3760/cma.j.cn115822-20201227-00283
[26]	Elfar M, Gaber L W, Sabek O, et al. The inflammatory cascade in acute pancreatitis: relevance to clinical disease[J]. Surg Clin North Am, 2007, 87: 1325-1340. DOI: 10.1016/j.suc.2007.09.002
[27]	Roth E, Zöch G, Schulz F, et al. Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis[J]. Clin Chem, 1985, 31: 1305-1309. DOI: 10.1093/clinchem/31.8.1305
[28]	Zaporozhchenko BS, Shilov VI. Changes in free amino acid plasma levels in patients with acute pancreatitis and their correction with early parenteral feeding[J]. Klin Khir, 2000(1): 13-15.
[29]	Sandstrom P, Trulsson L, Gasslander T, et al. Serum amino acid profile in patients with acute pancreatitis[J]. Amino Acids, 2008, 35: 225-231. DOI: 10.1007/s00726-007-0557-5
[30]	Adrych K, Smoczynski M, Stojek M, et al. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis[J]. World J Gastroenterol, 2010, 16: 4422-4427. DOI: 10.3748/wjg.v16.i35.4422
[31]	Jabłońska B, Mrowiec S. Nutritional Support in Patients with Severe Acute Pancreatitis-Current Standards[J]. Nutrients, 2021, 13: 1498. DOI: 10.3390/nu13051498
[32]	Al-Malki AL. Suppression of acute pancreatitis by L-lysine in mice[J]. BMC Complement Altern Med, 2015, 15: 193. DOI: 10.1186/s12906-015-0729-x
[33]	Sandstrom P, Brooke-Smith ME, Thomas AC, et al. Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis[J]. Pancreas, 2005, 30: e10-e15.
[34]	Zhang X, Jin T, Shi N, et al. Mechanisms of Pancreatic Injury Induced by Basic Amino Acids Differ Between L-Arginine, L-Ornithine, and L-Histidine[J]. Front Physiol, 2018, 9: 1922.
[35]	Saka M, Tüzün A, Ateᶊ Y, et al. Acute pancreatitis possibly due to arginine use: a case report[J]. Turk J Gastroenterol, 2004, 15: 56-58.
[36]	Smotkin J, Tenner S. Laboratory diagnostic tests in acute pancreatitis[J]. J Clin Gastroenterol, 2002, 34: 459-462. DOI: 10.1097/00004836-200204000-00018
[37]	Werner G, Klare I, Fleige C, et al. Vancomycin-resistant vanB-type Enterococcus faecium isolates expressing varying levels of vancomycin resistance and being highly prevalent among neonatal patients in a single ICU[J]. Antimicrob Resist Infect Control, 2012, 1: 21. DOI: 10.1186/2047-2994-1-21
[38]	Bassis CM, Moore NM, Lolans K, et al. Comparison of stool versus rectal swab samples and storage conditions on bacterial community profiles[J]. BMC Microbiol, 2017, 17: 78. DOI: 10.1186/s12866-017-0983-9

Cited By

Cited by

Periodical cited type(8)

1.	张福兴，俞唐唐，祝凯，陈明彤. 大柴胡汤加味联合芒硝外敷治疗急性胰腺炎的疗效观察及对炎症因子、胃肠激素、肠黏膜屏障功能和肠道菌群的影响. 中国中医药科技. 2024(03): 443-446 .
2.	葛佩鑫，贾博宜，张乃卫，张巧妍，张晓娜，郝少东，姜贤洋，关毅攀，程红杰. 胰瘅膏对急性胰腺炎大鼠肠道菌群及功能的影响. 中国中医急症. 2024(05): 790-795 .
3.	杨好，张敏，张博兴，宋亮. 肠道微环境影响急性胰腺炎的研究进展. 现代消化及介入诊疗. 2024(07): 876-880 .
4.	朱悦楠，李爱春，沈施恩，沈建伟. 急性胰腺炎基于肠道菌群和衍生代谢物的微环境变化及相关治疗策略. 中华胰腺病杂志. 2024(05): 387-392 .
5.	马增慧，马雪妮，苟铃珠，田文集，韩梦宇，张德奎. 急性胰腺炎严重程度预测的新型生物学标志物. 医学研究杂志. 2024(11): 155-159 .
6.	胡波，齐凌，卢玮，李菲. 血液病住院患者感染肠道致病菌的临床特点及危险因素. 检验医学与临床. 2023(06): 753-757 .
7.	梅道菊，喻露. 通腑清胰加减方中药灌肠在重症急性胰腺炎中的应用价值. 新疆医科大学学报. 2023(02): 244-248 .
8.	石靖祎，宿美玲，王立伟，刘倬希. 中药清肝利胆汤在重症急性胰腺炎治疗中的作用. 中外医疗. 2023(20): 181-185 .

Other cited types(5)

Get Citation

PDF

XML

Article Metrics

Article views (4325) PDF downloads (132) Cited by(13)

Address：	Room 302,Third Floor,Building 7, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, China
Tel：	010-69154261/4262
E - mail：	medj@pumch.cn mjpumch@126.com
Copyright of website：	Editorial Office of Medical Journal of Peking Union Medical College Hospital

Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study

Abstract

References

Cited by

Periodical cited type(8)

Other cited types(5)

Catalog

Article Metrics

Related

Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study

Abstract

References

Cited by

Periodical cited type(8)

Other cited types(5)

Catalog

Article Metrics

Related

Export File

Citation

Format

Content