Full Text:   <416>

Summary:  <69>

CLC number: 

On-line Access: 2024-04-07

Received: 2023-01-31

Revision Accepted: 2023-07-29

Crosschecked: 2024-04-07

Cited: 0

Clicked: 597

Citations:  Bibtex RefMan EndNote GB/T7714


Yulin GUO


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.4 P.271-279


Impacts of pancreatic exocrine insufficiency on gut microbiota

Author(s):  Yulin GUO, Feng CAO, Fei LI

Affiliation(s):  Department of General Surgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China; more

Corresponding email(s):   feili36@ccmu.edu.cn

Key Words:  Pancreatic exocrine insufficiency, Gut microbiota, Gut microbiome, Pancreatic enzyme replacement therapy

Share this article to: More |Next Article >>>

Yulin GUO, Feng CAO, Fei LI. Impacts of pancreatic exocrine insufficiency on gut microbiota[J]. Journal of Zhejiang University Science B, 2024, 25(4): 271-279.

@article{title="Impacts of pancreatic exocrine insufficiency on gut microbiota",
author="Yulin GUO, Feng CAO, Fei LI",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Impacts of pancreatic exocrine insufficiency on gut microbiota
%A Yulin GUO
%A Feng CAO
%A Fei LI
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 4
%P 271-279
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300070

T1 - Impacts of pancreatic exocrine insufficiency on gut microbiota
A1 - Yulin GUO
A1 - Feng CAO
A1 - Fei LI
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 4
SP - 271
EP - 279
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300070

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.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AdolphTE, MayrL, GrabherrF, et al., 2019. Pancreas‒microbiota cross talk in health and disease. Annu Rev Nutr, 39:249-266.

[2]AhujaM, SchwartzDM, TandonM, 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.

[3]BlakeAB, GuardBC, HonnefferJB, et al., 2019. Altered microbiota, fecal lactate, and fecal bile acids in dogs with gastrointestinal disease. PLoS ONE, 14(10):e0224454.

[4]BucklandAG, HeeleyEL, WiltonDC, 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.

[5]CampoL, EiselerS, ApfelT, et al., 2019. Fatty liver disease and gut microbiota: a comprehensive update. J Clin Transl Hepatol, 7(1):56-60.

[6]CasellasF, GuarnerL, VaqueroE, et al., 1998. Hydrogen breath test with glucose in exocrine pancreatic insufficiency. Pancreas, 16(4):481-486.

[7]ChairatanaP, ChuHT, CastilloPA, et al., 2016. Proteolysis triggers self-assembly and unmasks innate immune function of a human α-defensin peptide. Chem Sci, 7(3):1738-1752.

[8]DermadiD, ValoS, OllilaS, et al., 2017. Western diet deregulates bile acid homeostasis, cell proliferation, and tumorigenesis in colon. Cancer Res, 77(12):3352-3363.

[9]DuncanSH, LouisP, ThomsonJM, et al., 2009. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol, 11(8):2112-2122.

[10]DuttaSK, AnandK, GadaczTR, 1986. Bile salt malabsorption in pancreatic insufficiency secondary to alcoholic pancreatitis. Gastroenterology, 91(5):1243-1249.

[11]ForsmarkCE, 2018. Diagnosis and management of exocrine pancreatic insufficiency. Curr Treat Options Gastroenterol, 16(3):306-315.

[12]FrostF, KacprowskiT, RühlemannM, et al., 2019. Impaired exocrine pancreatic function associates with changes in intestinal microbiota composition and diversity. Gastroenterology, 156(4):1010-1015.

[13]FrostF, WeissFU, SendlerM, 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.

[14]GirdharK, SotoM, HuangQ, et al., 2022. Gut microbiota regulate pancreatic growth, exocrine function, and gut hormones. Diabetes, 71(5):945-960.

[15]HollemansRA, HallenslebenNDL, MagerDJ, et al., 2018. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis. Pancreatology, 18(3):253-262.

[16]HuanCM, KimD, OuPQ, et al., 2016. Mechanisms of interleukin-22’s beneficial effects in acute pancreatitis. World J Gastrointest Pathophysiol, 7(1):108-116.

[17]IovannaJ, FrigerioJM, DusettiN, et al., 1993. Lithostathine, an inhibitor of CaCO3, crystal growth in pancreatic juice, induces bacterial aggregation. Pancreas, 8(5):597-601.

[18]IsaiahA, ParambethJC, SteinerJM, et al., 2017. The fecal microbiome of dogs with exocrine pancreatic insufficiency. Anaerobe, 45:50-58.

[19]KellerJ, LayerP, 2005. Human pancreatic exocrine response to nutrients in health and disease. Gut, 54(S6):vi1-vi28.

[20]KempeneersMA, AliUA, IssaY, et al., 2020. Natural course and treatment of pancreatic exocrine insufficiency in a nationwide cohort of chronic pancreatitis. Pancreas, 49(2):242-248.

[21]KościuczukEM, LisowskiP, JarczakJ, et al., 2012. Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep, 39(12):10957-10970.

[22]LeeAA, BakerJR, WamstekerEJ, 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.

[23]LembckeB, KrausB, LankischPG, 1985. Small intestinal function in chronic relapsing pancreatitis. Hepatogastroenterology, 32(3):149-151.

[24]LiQR, WangCY, TangC, 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.

[25]LöhrJM, OliverMR, FrulloniL, 2013. Synopsis of recent guidelines on pancreatic exocrine insufficiency. United European Gastroenterol J, 1(2):79-83.

[26]LuWW, ChenX, NiJL, 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.

[27]MadsenJL, GraffJ, PhilipsenEK, 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.

[28]McCarlCA, PicardC, KhalilS, 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.

[29]NieYF, HuJ, YanXH, 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.

[30]NishiyamaH, NagaiT, KudoM, et al., 2018. Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice. Biochem Biophys Res Commun, 495(1):273-279.

[31]PetrovMS, 2019. Metabolic trifecta after pancreatitis: exocrine pancreatic dysfunction, altered gut microbiota, and new-onset diabetes. Clin Transl Gastroenterol, 10(10):e00086.

[32]PietznerM, BuddeK, RühlemannM, et al., 2021. Exocrine pancreatic function modulates plasma metabolites through changes in gut microbiota composition. J Clin Endocrinol Metab, 106(5):e2290-e2298.

[33]QinJJ, LiRQ, RaesJ, et al., 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285):59-65.

[34]ReijndersD, GoossensGH, HermesGDA, 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.

[35]RitzS, HahnD, WamiHT, 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.

[36]SandJ, NordbackI, 2009. Acute pancreatitis: risk of recurrence and late consequences of the disease. Nat Rev Gastroenterol Hepatol, 6(8):470-477.

[37]SeekatzAM, SchnizleinMK, KoenigsknechtMJ, et al., 2019. Spatial and temporal analysis of the stomach and small-intestinal microbiota in fasted healthy humans. mSphere, 4(2):e00126-19.

[38]SekirovI, RussellSL, AntunesLCM, et al., 2010. Gut microbiota in health and disease. Physiol Rev, 90(3):859-904.

[39]SeroussiE, BlumSE, KrifucksO, et al., 2018. Application of pancreatic phospholipase A2 for treatment of bovine mastitis. PLoS ONE, 13(8):e0203132.

[40]ShaoJW, GeTT, ChenSZ, et al., 2021. Role of bile acids in liver diseases mediated by the gut microbiome. World J Gastroenterol, 27(22):3010-3021.

[41]ShinJH, SeeleyRJ, 2019. Reg3 proteins as gut hormones? Endocrinology, 160(6):1506-1514.

[42]SileikieneV, MosenthinR, TafajM, 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.

[43]SimpsonKW, BattRM, JonesD, 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.

[44]SunJ, FurioL, MecheriR, 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.

[45]TanCC, LingZX, HuangY, et al., 2015. Dysbiosis of intestinal microbiota associated with inflammation involved in the progression of acute pancreatitis. Pancreas, 44(6):868-875.

[46]ThomasPD, ForbesA, GreenJ, et al., 2003. Guidelines for the investigation of chronic diarrhoea, 2nd edition. Gut, 52(S5):v1-v15.

[47]ThomasRM, JobinC, 2020. Microbiota in pancreatic health and disease: the next frontier in microbiome research. Nat Rev Gastroenterol Hepatol, 17:53-64.

[48]TilgH, AdolphTE, 2017. Beyond digestion: the pancreas shapes intestinal microbiota and immunity. Cell Metab, 25(3):495-496.

[49]TrespiE, FerrieriA, 1999. Intestinal bacterial overgrowth during chronic pancreatitis. Curr Med Res Opin, 15(1):47-52.

[50]VangaRR, TanselA, SidiqS, 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.

[51]WestermarckE, MyllysV, AhoM, 1993. Effect of treatment on the jejunal and colonic bacterial flora of dogs with exocrine pancreatic insufficiency. Pancreas, 8(5):559-562.

[52]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.

[53]ZarrinparA, ChaixA, YoosephS, et al., 2014. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab, 20(6):1006-1017.

[54]ZhangZW, TanakaI, PanZ, et al., 2022. Intestinal homeostasis and inflammation: gut microbiota at the crossroads of pancreas‒intestinal barrier axis. Eur J Immunol, 52(7):1035-1046.

[55]ZhouCH, MengYT, XuJJ, et al., 2020. Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis. Pancreatology, 20(1):16-24.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE