Impacts of pancreatic exocrine insufficiency on gut microbiota

Yulin GUO; Feng CAO; Fei LI

doi:10.1631/jzus.B2300070

Your Location：

Home >

Browse articles >

Impacts of pancreatic exocrine insufficiency on gut microbiota

Scan for full text

Alert me when the article has been cited

Submit

Review | Updated：2024-04-07

Impacts of pancreatic exocrine insufficiency on gut microbiota
Impacts of pancreatic exocrine insufficiency on gut microbiota
胰腺外分泌功能不全对肠道微生物群的影响
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 4, Pages: 271-279(2024)
Affiliations：

1.Department of General Surgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
2.Acute Pancreatitis Clinical Center of Capital Medical University, Beijing 100053, China
Funds：
DOI：10.1631/jzus.B2300070
CLC：
CSTR：
Published： 15 April 2024 ，

Received： 31 January 2023 ，

Revised： 29 July 2023 ，

郭玉霖,曹锋,李非.胰腺外分泌功能不全对肠道微生物群的影响[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(04):271-279.

Yulin GUO, Feng CAO, Fei LI. Impacts of pancreatic exocrine insufficiency on gut microbiota. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(4):271-279(2024)
郭玉霖,曹锋,李非.胰腺外分泌功能不全对肠道微生物群的影响[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(04):271-279. DOI： 10.1631/jzus.B2300070.

Yulin GUO, Feng CAO, Fei LI. Impacts of pancreatic exocrine insufficiency on gut microbiota. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(4):271-279(2024) DOI： 10.1631/jzus.B2300070.

摘要

胰腺外分泌功能不全（PEI）可由多种疾病引起，包括慢性胰腺炎、急性胰腺炎、胰腺切除术后等。PEI其主要发病机制与胰蛋白酶合成下降、胰液流动紊乱、分泌反馈失衡有关。动物研究表明：PEI可诱导肠道细菌过度生长和生态失调，其中乳杆菌和双歧杆菌的丰度增加最为多见；肠道细菌过度生长和生态失调可通过胰酶替代治疗得到部分逆转。临床研究也证实PEI与肠道菌群失调之间存在关联。胰脏外分泌水平的下降，伴随PEI产生的十二指肠pH值的改变，以及PEI引起的胆盐吸收不良，这可能是PEI导致肠道菌群丰度和组成发生改变的潜在作用机制。反之，肠道微生物群也可能通过潜在的双向调节影响胰腺外分泌腺泡的功能。展望未来，仍需要更多的高质量研究来揭示胰腺外分泌不足对肠道微生物群影响的机制。

Abstract

Pancreatic exocrine insufficiency (PEI) can be induced by various kinds of diseases

including chronic pancreatitis

acute pancreatitis

and post-pancreatectomy. The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis

disorder of pancreatic fluid flow

and imbalance of secretion feedback. Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis

with the abundance of

Lactobacillus

and

Bifidobacterium

increasing the most

which could be partially reversed by pancreatic enzyme replacement therapy. Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota. Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota. In turn

the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk. Going forward

more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

关键词

胰腺外分泌不足肠道微生物群肠道微生物组胰酶替代疗法

Keywords

Pancreatic exocrine insufficiencyGut microbiotaGut microbiomePancreatic enzyme replacement therapy

references

Adolph TE, Mayr L, Grabherr F, et al., 2019. Pancreas‒microbiota cross talk in health and disease. Annu Rev Nutr, 39:249-266. https://doi.org/10.1146/annurev-nutr-082018-124306https://doi.org/10.1146/annurev-nutr-082018-124306

Ahuja M, Schwartz DM, Tandon M, et al., 2017. Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab, 25(3):635-646. https://doi.org/10.1016/j.cmet.2017.02.007https://doi.org/10.1016/j.cmet.2017.02.007

Blake AB, Guard BC, Honneffer JB, et al., 2019. Altered microbiota, fecal lactate, and fecal bile acids in dogs with gastrointestinal disease. PLoS ONE, 14(10):e0224454. https://doi.org/10.1371/journal.pone.0224454https://doi.org/10.1371/journal.pone.0224454

Buckland AG, Heeley EL, Wilton DC, 2000. Bacterial cell membrane hydrolysis by secreted phospholipases A2: a major physiological role of human group IIa sPLA2 involving both bacterial cell wall penetration and interfacial catalysis. Biochim Biophys Acta Mol Cell Biol Lipids, 1484(2-3):195-206. https://doi.org/10.1016/s1388-1981(00)00018-4https://doi.org/10.1016/s1388-1981(00)00018-4

Campo L, Eiseler S, Apfel T, et al., 2019. Fatty liver disease and gut microbiota: a comprehensive update. J Clin Transl Hepatol, 7(1):56-60. https://doi.org/10.14218/JCTH.2018.00008https://doi.org/10.14218/JCTH.2018.00008

Casellas F, Guarner L, Vaquero E, et al., 1998. Hydrogen breath test with glucose in exocrine pancreatic insufficiency. Pancreas, 16(4):481-486. https://doi.org/10.1097/00006676-199805000-00004https://doi.org/10.1097/00006676-199805000-00004

Chairatana P, Chu HT, Castillo PA, et al., 2016. Proteolysis triggers self-assembly and unmasks innate immune function of a human α-defensin peptide. Chem Sci, 7(3):1738-1752. https://doi.org/10.1039/C5SC04194Ehttps://doi.org/10.1039/C5SC04194E

Dermadi D, Valo S, Ollila S, et al., 2017. Western diet deregulates bile acid homeostasis, cell proliferation, and tumorigenesis in colon. Cancer Res, 77(12):3352-3363. https://doi.org/10.1158/0008-5472.CAN-16-2860https://doi.org/10.1158/0008-5472.CAN-16-2860

Duncan SH, Louis P, Thomson JM, et al., 2009. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol, 11(8):2112-2122. https://doi.org/10.1111/j.1462-2920.2009.01931.xhttps://doi.org/10.1111/j.1462-2920.2009.01931.x

Dutta SK, Anand K, Gadacz TR, 1986. Bile salt malabsorption in pancreatic insufficiency secondary to alcoholic pancreatitis. Gastroenterology, 91(5):1243-1249. https://doi.org/10.1016/s0016-5085(86)80023-3https://doi.org/10.1016/s0016-5085(86)80023-3

Forsmark CE, 2018. Diagnosis and management of exocrine pancreatic insufficiency. Curr Treat Options Gastroenterol, 16(3):306-315. https://doi.org/10.1007/s11938-018-0186-yhttps://doi.org/10.1007/s11938-018-0186-y

Frost F, Kacprowski T, Rühlemann M, et al., 2019. Impaired exocrine pancreatic function associates with changes in intestinal microbiota composition and diversity. Gastroenterology, 156(4):1010-1015. https://doi.org/10.1053/j.gastro.2018.10.047https://doi.org/10.1053/j.gastro.2018.10.047

Frost F, Weiss FU, Sendler M, et al., 2020. The gut microbiome in patients with chronic pancreatitis is characterized by significant dysbiosis and overgrowth by opportunistic pathogens. Clin Transl Gastroenterol, 11(9):e00232. https://doi.org/10.14309/ctg.0000000000000232https://doi.org/10.14309/ctg.0000000000000232

Girdhar K, Soto M, Huang Q, et al., 2022. Gut microbiota regulate pancreatic growth, exocrine function, and gut hormones. Diabetes, 71(5):945-960. https://doi.org/10.2337/db21-0382https://doi.org/10.2337/db21-0382

Hollemans RA, Hallensleben NDL, Mager DJ, et al., 2018. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis. Pancreatology, 18(3):253-262. https://doi.org/10.1016/j.pan.2018.02.009https://doi.org/10.1016/j.pan.2018.02.009

Huan CM, Kim D, Ou PQ, et al., 2016. Mechanisms of interleukin-22’s beneficial effects in acute pancreatitis. World J Gastrointest Pathophysiol, 7(1):108-116. https://doi.org/10.4291/wjgp.v7.i1.108https://doi.org/10.4291/wjgp.v7.i1.108

Iovanna J, Frigerio JM, Dusetti N, et al., 1993. Lithostathine, an inhibitor of CaCO3, crystal growth in pancreatic juice, induces bacterial aggregation. Pancreas, 8(5):597-601. https://doi.org/10.1097/00006676-199309000-00011https://doi.org/10.1097/00006676-199309000-00011

Isaiah A, Parambeth JC, Steiner JM, et al., 2017. The fecal microbiome of dogs with exocrine pancreatic insufficiency. Anaerobe, 45:50-58. https://doi.org/10.1016/j.anaerobe.2017.02.010https://doi.org/10.1016/j.anaerobe.2017.02.010

Keller J, Layer P, 2005. Human pancreatic exocrine response to nutrients in health and disease. Gut, 54(S6):vi1-vi28. https://doi.org/10.1136/gut.2005.065946https://doi.org/10.1136/gut.2005.065946

Kempeneers MA, Ali UA, Issa Y, et al., 2020. Natural course and treatment of pancreatic exocrine insufficiency in a nationwide cohort of chronic pancreatitis. Pancreas, 49(2):242-248. https://doi.org/10.1097/MPA.0000000000001473https://doi.org/10.1097/MPA.0000000000001473

Kościuczuk EM, Lisowski P, Jarczak J, et al., 2012. Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep, 39(12):10957-10970. https://doi.org/10.1007/s11033-012-1997-xhttps://doi.org/10.1007/s11033-012-1997-x

Lee AA, Baker JR, Wamsteker EJ, et al., 2019. Small intestinal bacterial overgrowth is common in chronic pancreatitis and associates with diabetes, chronic pancreatitis severity, low zinc levels, and opiate use. Am J Gastroenterol, 114(7):1163-1171. https://doi.org/10.14309/ajg.0000000000000200https://doi.org/10.14309/ajg.0000000000000200

Lembcke B, Kraus B, Lankisch PG, 1985. Small intestinal function in chronic relapsing pancreatitis. Hepatogastroenterology, 32(3):149-151.

Li QR, Wang CY, Tang C, et al., 2013. Bacteremia in patients with acute pancreatitis as revealed by 16S ribosomal RNA gene-based techniques. Crit Care Med, 41(8):1938-1950. https://doi.org/10.1097/CCM.0b013e31828a3dbahttps://doi.org/10.1097/CCM.0b013e31828a3dba

Löhr JM, Oliver MR, Frulloni L, 2013. Synopsis of recent guidelines on pancreatic exocrine insufficiency. United European Gastroenterol J, 1(2):79-83. https://doi.org/10.1177/2050640613476500https://doi.org/10.1177/2050640613476500

Lu WW, Chen X, Ni JL, et al., 2021. The role of gut microbiota in the pathogenesis and treatment of acute pancreatitis: a narrative review. Ann Palliat Med, 10(3):3445-3451. https://doi.org/10.21037/apm-21-429https://doi.org/10.21037/apm-21-429

Madsen JL, Graff J, Philipsen EK, et al., 2003. Bile acid malabsorption or disturbed intestinal permeability in patients treated with enzyme substitution for exocrine pancreatic insufficiency is not caused by bacterial overgrowth. Pancreas, 26(2):130-133. https://doi.org/10.1097/00006676-200303000-00007https://doi.org/10.1097/00006676-200303000-00007

McCarl CA, Picard C, Khalil S, et al., 2009. ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia. J Allergy Clin Immunol, 124(6):1311-1318.e7. https://doi.org/10.1016/j.jaci.2009.10.007https://doi.org/10.1016/j.jaci.2009.10.007

Nie YF, Hu J, Yan XH, 2015. Cross-talk between bile acids and intestinal microbiota in host metabolism and health. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 16(6):436-446. https://doi.org/10.1631/jzus.B1400327https://doi.org/10.1631/jzus.B1400327

Nishiyama H, Nagai T, Kudo M, et al., 2018. Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice. Biochem Biophys Res Commun, 495(1):273-279. https://doi.org/10.1016/j.bbrc.2017.10.130https://doi.org/10.1016/j.bbrc.2017.10.130

Petrov MS, 2019. Metabolic trifecta after pancreatitis: exocrine pancreatic dysfunction, altered gut microbiota, and new-onset diabetes. Clin Transl Gastroenterol, 10(10):e00086. https://doi.org/10.14309/ctg.0000000000000086https://doi.org/10.14309/ctg.0000000000000086

Pietzner M, Budde K, Rühlemann M, et al., 2021. Exocrine pancreatic function modulates plasma metabolites through changes in gut microbiota composition. J Clin Endocrinol Metab, 106(5):e2290-e2298. https://doi.org/10.1210/clinem/dgaa961https://doi.org/10.1210/clinem/dgaa961

Qin JJ, Li RQ, Raes J, et al., 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285):59-65. https://doi.org/10.1038/nature08821https://doi.org/10.1038/nature08821

Reijnders D, Goossens GH, Hermes GDA, et al., 2016. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: a randomized double-blind placebo-controlled trial. Cell Metab, 24(1):63-74. https://doi.org/10.1016/j.cmet.2016.06.016https://doi.org/10.1016/j.cmet.2016.06.016

Ritz S, Hahn D, Wami HT, et al., 2020. Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency. Microb Cell Fact, 19:221. https://doi.org/10.1186/s12934-020-01482-2https://doi.org/10.1186/s12934-020-01482-2

Sand J, Nordback I, 2009. Acute pancreatitis: risk of recurrence and late consequences of the disease. Nat Rev Gastroenterol Hepatol, 6(8):470-477. https://doi.org/10.1038/nrgastro.2009.106https://doi.org/10.1038/nrgastro.2009.106

Seekatz AM, Schnizlein MK, Koenigsknecht MJ, et al., 2019. Spatial and temporal analysis of the stomach and small-intestinal microbiota in fasted healthy humans. mSphere, 4(2):e00126-19. https://doi.org/10.1128/mSphere.00126-19https://doi.org/10.1128/mSphere.00126-19

Sekirov I, Russell SL, Antunes LCM, et al., 2010. Gut microbiota in health and disease. Physiol Rev, 90(3):859-904. https://doi.org/10.1152/physrev.00045.2009https://doi.org/10.1152/physrev.00045.2009

Seroussi E, Blum SE, Krifucks O, et al., 2018. Application of pancreatic phospholipase A2 for treatment of bovine mastitis. PLoS ONE, 13(8):e0203132. https://doi.org/10.1371/journal.pone.0203132https://doi.org/10.1371/journal.pone.0203132

Shao JW, Ge TT, Chen SZ, et al., 2021. Role of bile acids in liver diseases mediated by the gut microbiome. World J Gastroenterol, 27(22):3010-3021. https://doi.org/10.3748/wjg.v27.i22.3010https://doi.org/10.3748/wjg.v27.i22.3010

Shin JH, Seeley RJ, 2019. Reg3 proteins as gut hormones? Endocrinology, 160(6):1506-1514. https://doi.org/10.1210/en.2019-00073https://doi.org/10.1210/en.2019-00073

Sileikiene V, Mosenthin R, Tafaj M, et al., 2005. Effect of short chain fatty acids infused intraileally on interdigestive exocrine pancreatic secretions in growing pigs. J Anim Physiol Anim Nutr (Berl), 89(7-8): 253-259. https://doi.org/10.1111/j.1439-0396.2005.00511.xhttps://doi.org/10.1111/j.1439-0396.2005.00511.x

Simpson KW, Batt RM, Jones D, et al., 1990. Effects of exocrine pancreatic insufficiency and replacement therapy on the bacterial flora of the duodenum in dogs. Am J Vet Res, 51(2):203-206.

Sun J, Furio L, Mecheri R, et al., 2015. Pancreatic β-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota. Immunity, 43(2):304-317. https://doi.org/10.1016/j.immuni.2015.07.013https://doi.org/10.1016/j.immuni.2015.07.013

Tan CC, Ling ZX, Huang Y, et al., 2015. Dysbiosis of intestinal microbiota associated with inflammation involved in the progression of acute pancreatitis. Pancreas, 44(6):868-875. https://doi.org/10.1097/MPA.0000000000000355https://doi.org/10.1097/MPA.0000000000000355

Thomas PD, Forbes A, Green J, et al., 2003. Guidelines for the investigation of chronic diarrhoea, 2nd edition. Gut, 52(S5):v1-v15. https://doi.org/10.1136/gut.52.suppl_5.v1https://doi.org/10.1136/gut.52.suppl_5.v1

Thomas RM, Jobin C, 2020. Microbiota in pancreatic health and disease: the next frontier in microbiome research. Nat Rev Gastroenterol Hepatol, 17:53-64. https://doi.org/10.1038/s41575-019-0242-7https://doi.org/10.1038/s41575-019-0242-7

Tilg H, Adolph TE, 2017. Beyond digestion: the pancreas shapes intestinal microbiota and immunity. Cell Metab, 25(3):495-496. https://doi.org/10.1016/j.cmet.2017.02.018https://doi.org/10.1016/j.cmet.2017.02.018

Trespi E, Ferrieri A, 1999. Intestinal bacterial overgrowth during chronic pancreatitis. Curr Med Res Opin, 15(1):47-52. https://doi.org/10.1185/03007999909115173https://doi.org/10.1185/03007999909115173

Vanga RR, Tansel A, Sidiq S, et al., 2018. Diagnostic performance of measurement of fecal elastase-1 in detection of exocrine pancreatic insufficiency: systematic review and meta-analysis. Clin Gastroenterol Hepatol, 16(8):1220-1228.e4. https://doi.org/10.1016/j.cgh.2018.01.027https://doi.org/10.1016/j.cgh.2018.01.027

Westermarck E, Myllys V, Aho M, 1993. Effect of treatment on the jejunal and colonic bacterial flora of dogs with exocrine pancreatic insufficiency. Pancreas, 8(5):559-562. https://doi.org/10.1097/00006676-199309000-00005https://doi.org/10.1097/00006676-199309000-00005

Working Party of the Australasian Pancreatic Club, 2016. Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency. Pancreatology, 16(2):164-180. https://doi.org/10.1016/j.pan.2015.12.006https://doi.org/10.1016/j.pan.2015.12.006

Zarrinpar A, Chaix A, Yooseph S, et al., 2014. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab, 20(6):1006-1017. https://doi.org/10.1016/j.cmet.2014.11.008https://doi.org/10.1016/j.cmet.2014.11.008

Zhang ZW, Tanaka I, Pan Z, et al., 2022. Intestinal homeostasis and inflammation: gut microbiota at the crossroads of pancreas‒intestinal barrier axis. Eur J Immunol, 52(7):1035-1046. https://doi.org/10.1002/eji.202149532https://doi.org/10.1002/eji.202149532

Zhou CH, Meng YT, Xu JJ, et al., 2020. Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis. Pancreatology, 20(1):16-24. https://doi.org/10.1016/j.pan.2019.11.013https://doi.org/10.1016/j.pan.2019.11.013

More>

Views

Downloads

CSCD

Tools

Publicity Resources

Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases

Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress

Related Author

No data

Related Institution

School of Medicine, Southeast University

Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital

State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University

School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji’nan

School of Traditional Chinese Medicine,Shandong Co-Innovation Center of Classic Traditional Chinese Medicine Formula, Shandong University of Traditional Chinese Medicine, Ji’nan

Address：Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou, China Postal code：310027
Tel：+86-571-87952783 Email：cjzhang@zju.edu.cn
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰