Understanding the Effects of Metabolites on the Gut Microbiome and Severe Acute Pancreatitis

Shijie Ye, Chenli Si, Jie Deng, Xiaohu Chen, Lingming Kong, Xiang Zhou, Weiming Wang, Shijie Ye, Chenli Si, Jie Deng, Xiaohu Chen, Lingming Kong, Xiang Zhou, Weiming Wang

Abstract

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. The severity is classified as mild (MAP), moderately severe (MSAP), or severe (SAP). In patients with SAP, organ dysfunction can occur in the early stage of the disease course, accompanied by secondary infection, with a mortality rate of 36%-50%. In the late stage SAP, infection-related complications caused by pancreatic necrotic tissue and peripancreatic effusion are the main causes of death in patients. Dysbacteriosis of intestinal microflora, barrier dysfunction of intestinal mucosa, and translocation of enteric bacteria are considered to be the main causes of infection of pancreatic necrotic tissue and peripancreatic effusion. During the past few years, increasing attention has been paid to the metabolic activities of intestinal microflora in SAP, which plays an important role in the metabolic activities of the human body. This review is aimed at bringing together the most recent findings and advances regarding the gut microbial community and associated gut microbial community metabolites and illustrating the role of these metabolites in disease progression in severe acute pancreatitis. We hope that this review will provide new ideas and schemes for the treatment of SAP in the clinical settings.

Conflict of interest statement

All authors declare no potential conflicts of interest.

Copyright © 2021 Shijie Ye et al.

References

    1. Pang Y., Kartsonaki C., Turnbull I., et al. Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: a prospective cohort study of 0.5 million people. PLOS Medicine . 2018;15(8):p. e1002618. doi: 10.1371/journal.pmed.1002618.
    1. Gukovskaya A. S., Gorelick F. S., Groblewski G. E., et al. Recent insights into the pathogenic mechanism of pancreatitis: role of acinar cell organelle disorders. Pancreas . 2019;48(4):459–470. doi: 10.1097/MPA.0000000000001298.
    1. Rakonczay Z. J., Hegyi P., Takács T., McCarroll J., Saluja A. K. The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut . 2008;57(2):259–267. doi: 10.1136/gut.2007.124115.
    1. Habtezion A. Inflammation in acute and chronic pancreatitis. Current Opinion in Gastroenterology . 2015;31(5):395–399. doi: 10.1097/MOG.0000000000000195.
    1. Banks P. A., Bollen T. L., Dervenis C., et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut . 2013;62(1):102–111. doi: 10.1136/gutjnl-2012-302779.
    1. Lankisch P. G., Apte M., Banks P. A. Acute pancreatitis. Lancet . 2015;386(9988):85–96. doi: 10.1016/S0140-6736(14)60649-8.
    1. Wang F., Li Q., Wang C., Tang C., Li J. Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion injury. PLoS One . 2012;7(7, article e42027) doi: 10.1371/journal.pone.0042027.
    1. Tan C., Ling Z., Huang Y., et al. Dysbiosis of intestinal microbiota associated with inflammation involved in the progression of acute pancreatitis. Pancreas . 2015;44(6):868–875. doi: 10.1097/MPA.0000000000000355.
    1. Gómez-Hurtado I., Santacruz A., Peiró G., et al. Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis. PLoS One . 2011;6(7, article e23037) doi: 10.1371/journal.pone.0023037.
    1. Liu J., Huang L., Luo M., Xia X. Bacterial translocation in acute pancreatitis. Critical Reviews in Microbiology . 2019;45(5-6):539–547. doi: 10.1080/1040841X.2019.1621795.
    1. Portelli M., Jones C. D. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary & Pancreatic Diseases International . 2017;16(2):155–159. doi: 10.1016/S1499-3872(16)60163-7.
    1. Del V. B. G., Gesuale C., Varanese M., Monteleone G., Paoluzi O. A. Idiopathic acute pancreatitis: a review on etiology and diagnostic work-up. Clinical Journal of Gastroenterology . 2019;12(6):511–524. doi: 10.1007/s12328-019-00987-7.
    1. Roberts S. E., Morrison-Rees S., John A., Williams J. G., Brown T. H., Samuel D. G. The incidence and aetiology of acute pancreatitis across Europe. Pancreatology . 2017;17(2):155–165. doi: 10.1016/j.pan.2017.01.005.
    1. De-Madaria E., Capurso G. COVID-19 and acute pancreatitis: examining the causality. Nature Reviews. Gastroenterology & Hepatology . 2021;18(1):3–4. doi: 10.1038/s41575-020-00389-y.
    1. Yang A. L., McNabb-Baltar J. Hypertriglyceridemia and acute pancreatitis. Pancreatology . 2020;20(5):795–800. doi: 10.1016/j.pan.2020.06.005.
    1. Boxhoorn L., Voermans R. P., Bouwense S. A., et al. Acute pancreatitis. Lancet . 2020;396(10252):726–734. doi: 10.1016/S0140-6736(20)31310-6.
    1. Lee P. J., Papachristou G. I. New insights into acute pancreatitis. Nature Reviews. Gastroenterology & Hepatology . 2019;16(8):479–496. doi: 10.1038/s41575-019-0158-2.
    1. Das N. K., Schwartz A. J., Barthel G., et al. Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metabolism . 2020;31(1):115–130.e6. doi: 10.1016/j.cmet.2019.10.005.
    1. Tang D., Chen X., Kang R., Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Research . 2021;31(2):107–125. doi: 10.1038/s41422-020-00441-1.
    1. Zheng J., Conrad M. The metabolic underpinnings of ferroptosis. Cell Metabolism . 2020;32(6):920–937. doi: 10.1016/j.cmet.2020.10.011.
    1. Nicholson J. K., Holmes E., Kinross J., et al. Host-gut microbiota metabolic interactions. Science . 2012;336(6086):1262–1267. doi: 10.1126/science.1223813.
    1. Diamant M., Blaak E. E., de Vos W. M. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obesity Reviews . 2011;12(4):272–281. doi: 10.1111/j.1467-789X.2010.00797.x.
    1. Tremaroli V., Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature . 2012;489(7415):242–249. doi: 10.1038/nature11552.
    1. Schmidt T., Raes J., Bork P. The human gut microbiome: from association to modulation. Cell . 2018;172(6):1198–1215. doi: 10.1016/j.cell.2018.02.044.
    1. O'Hara A. M., Shanahan F. The gut flora as a forgotten organ. EMBO Reports . 2006;7(7):688–693. doi: 10.1038/sj.embor.7400731.
    1. Aagaard K., Ma J., Antony K. M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Science Translational Medicine . 2014;6(237):p. 237ra65. doi: 10.1126/scitranslmed.3008599.
    1. Jiménez E., Fernández L., Marín M. L., et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Current Microbiology . 2005;51(4):270–274. doi: 10.1007/s00284-005-0020-3.
    1. DiGiulio D. B., Romero R., Amogan H. P., et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One . 2008;3(8, article e3056) doi: 10.1371/journal.pone.0003056.
    1. Yatsunenko T., Rey F. E., Manary M. J., et al. Human gut microbiome viewed across age and geography. Nature . 2012;486(7402):222–227. doi: 10.1038/nature11053.
    1. Ursell L. K., Clemente J. C., Rideout J. R., Gevers D., Caporaso J. G., Knight R. The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. The Journal of Allergy and Clinical Immunology . 2012;129(5):1204–1208. doi: 10.1016/j.jaci.2012.03.010.
    1. Nagpal R., Yadav H. Bacterial translocation from the gut to the distant organs: an overview. Annals of Nutrition & Metabolism . 2017;71(Suppl 1):11–16. doi: 10.1159/000479918.
    1. Frossard J. L., Steer M. L., Pastor C. M. Acute pancreatitis. Lancet . 2008;371(9607):143–152. doi: 10.1016/S0140-6736(08)60107-5.
    1. Wen W., Zheng H., Jiang Y., et al. Effect of intestinal epithelial autophagy on bacterial translocation in severe acute pancreatitis. Clinics and Research in Hepatology and Gastroenterology . 2017;41(6):703–710. doi: 10.1016/j.clinre.2017.03.007.
    1. Li Q., Wang C., Tang C., He Q., Li N., Li J. Bacteremia in patients with acute pancreatitis as revealed by 16S ribosomal RNA gene-based techniques. Critical Care Medicine . 2013;41(8):1938–1950. doi: 10.1097/CCM.0b013e31828a3dba.
    1. Vancamelbeke M., Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Review of Gastroenterology & Hepatology . 2017;11(9):821–834. doi: 10.1080/17474124.2017.1343143.
    1. 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. PLoS One . 2017;12(4, article e0176583) doi: 10.1371/journal.pone.0176583.
    1. Zhu Y., He C., Li X., et al. Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. Journal of Gastroenterology . 2019;54(4):347–358. doi: 10.1007/s00535-018-1529-0.
    1. Tian R., Tan J. T., Wang R. L., Xie H., Qian Y. B., Yu K. L. The role of intestinal mucosa oxidative stress in gut barrier dysfunction of severe acute pancreatitis. European Review for Medical and Pharmacological Sciences . 2013;17(3):349–355.
    1. Bunker J. J., Flynn T. M., Koval J. C., et al. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin a. Immunity . 2015;43(3):541–553. doi: 10.1016/j.immuni.2015.08.007.
    1. Bunker J. J., Bendelac A. IgA responses to microbiota. Immunity . 2018;49(2):211–224. doi: 10.1016/j.immuni.2018.08.011.
    1. Macpherson A. J., Yilmaz B., Limenitakis J. P., Ganal-Vonarburg S. C. IgA function in relation to the intestinal microbiota. Annual Review of Immunology . 2018;36(1):359–381. doi: 10.1146/annurev-immunol-042617-053238.
    1. Li X., He C., Li N., et al. The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice. Gut Microbes . 2020;11(6):1774–1789. doi: 10.1080/19490976.2020.1770042.
    1. van Dijk S. M., Hallensleben N., van Santvoort H. C., et al. Acute pancreatitis: recent advances through randomised trials. Gut . 2017;66(11):2024–2032. doi: 10.1136/gutjnl-2016-313595.
    1. Zerem E. Treatment of severe acute pancreatitis and its complications. World Journal of Gastroenterology . 2014;20(38):13879–13892. doi: 10.3748/wjg.v20.i38.13879.
    1. Capurso G., Zerboni G., Signoretti M., et al. Role of the gut barrier in acute pancreatitis. Journal of Clinical Gastroenterology . 2012;46(Suppl):S46–S51. doi: 10.1097/MCG.0b013e3182652096.
    1. Sah R. P., Garg P., Saluja A. K. Pathogenic mechanisms of acute pancreatitis. Current Opinion in Gastroenterology . 2012;28(5):507–515. doi: 10.1097/MOG.0b013e3283567f52.
    1. Bongaerts G. P., Severijnen R. S. A reassessment of the PROPATRIA study and its implications for probiotic therapy. Nature Biotechnology . 2016;34(1):55–63. doi: 10.1038/nbt.3436.
    1. Besselink M. G. H., van Santvoort H. C., Buskens E., et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet . 2008;371(9613):651–659. doi: 10.1016/S0140-6736(08)60207-X.
    1. Kamada N., Kim Y. G., Sham H. P., et al. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science . 2012;336(6086):1325–1329. doi: 10.1126/science.1222195.
    1. Macia L., Tan J., Vieira A. T., et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nature Communications . 2015;6(1):p. 6734. doi: 10.1038/ncomms7734.
    1. Venegas D. P., De la Fuente M. K., Landskron G., et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in Immunology . 2019;10:p. 277. doi: 10.3389/fimmu.2019.00277.
    1. Louis P., Flint H. J. Formation of propionate and butyrate by the human colonic microbiota. Environmental Microbiology . 2017;19(1):29–41. doi: 10.1111/1462-2920.13589.
    1. de Aguiar V. T., Tarling E. J., Edwards P. A. Pleiotropic roles of bile acids in metabolism. Cell Metabolism . 2013;17(5):657–669. doi: 10.1016/j.cmet.2013.03.013.
    1. Wahlstrom A., Sayin S. I., Marschall H. U., Backhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metabolism . 2016;24(1):41–50. doi: 10.1016/j.cmet.2016.05.005.
    1. Tofalo R., Cocchi S., Suzzi G. Polyamines and gut microbiota. Frontiers in Nutrition . 2019;6:p. 16. doi: 10.3389/fnut.2019.00016.
    1. Chen J., Rao J. N., Zou T., et al. Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity. American Journal of Physiology. Gastrointestinal and Liver Physiology . 2007;293(3):G568–G576. doi: 10.1152/ajpgi.00201.2007.
    1. Roager H. M., Licht T. R. Microbial tryptophan catabolites in health and disease. Nature Communications . 2018;9(1):p. 3294. doi: 10.1038/s41467-018-05470-4.
    1. Dodd D., Spitzer M. H., Van Treuren W., et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature . 2017;551(7682):648–652. doi: 10.1038/nature24661.
    1. Gao J., Li Y., Wan Y., et al. A novel postbiotic from Lactobacillus rhamnosus GG with a beneficial effect on intestinal barrier function. Frontiers in Microbiology . 2019;10:p. 477. doi: 10.3389/fmicb.2019.00477.
    1. Breyner N. M., Michon C., de Sousa C. S., et al. Microbial anti-inflammatory molecule (MAM) from Faecalibacterium prausnitzii shows a protective effect on DNBS and DSS-induced colitis model in mice through inhibition of NF-κB pathway. Frontiers in Microbiology . 2017;8 doi: 10.3389/fmicb.2017.00114.
    1. Morrison D. J., Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes . 2016;7(3):189–200. doi: 10.1080/19490976.2015.1134082.
    1. Louis P., Young P., Holtrop G., Flint H. J. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA: acetate CoA-transferase gene. Environmental Microbiology . 2010;12(2):304–314. doi: 10.1111/j.1462-2920.2009.02066.x.
    1. Tan J., McKenzie C., Potamitis M., Thorburn A. N., Mackay C. R., Macia L. The role of short-chain fatty acids in health and disease. Advances in Immunology . 2014;121:91–119. doi: 10.1016/B978-0-12-800100-4.00003-9.
    1. Richards J. L., Yap Y. A., McLeod K. H., Mackay C. R., Marino E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunology. . 2016;5(5, article e82) doi: 10.1038/cti.2016.29.
    1. Zeng H., Umar S., Rust B., Lazarova D., Bordonaro M. Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation, and cancer. International Journal of Molecular Sciences . 2019;20(5):p. 1214. doi: 10.3390/ijms20051214.
    1. Singh N., Gurav A., Sivaprakasam S., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity . 2014;40(1):128–139. doi: 10.1016/j.immuni.2013.12.007.
    1. Zhao Y., Chen F., Wu W., et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunology . 2018;11(3):752–762. doi: 10.1038/mi.2017.118.
    1. Liu H., Wang J., He T., et al. Butyrate: a double-edged sword for health? Advances in Nutrition . 2018;9(1):21–29. doi: 10.1093/advances/nmx009.
    1. Bultman S. J. Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention. Clinical Cancer Research . 2014;20(4):799–803. doi: 10.1158/1078-0432.CCR-13-2483.
    1. Geirnaert A., Calatayud M., Grootaert C., et al. Butyrate-producing bacteria supplemented in vitro to Crohn's disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Scientific Reports . 2017;7(1):p. 11450. doi: 10.1038/s41598-017-11734-8.
    1. D’Souza W. N., Douangpanya J., Mu S., et al. Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses. PLoS One . 2017;12(7, article e0180190) doi: 10.1371/journal.pone.0180190.
    1. Riviere A., Selak M., Lantin D., Leroy F., De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Frontiers in Microbiology . 2016;7:p. 979. doi: 10.3389/fmicb.2016.00979.
    1. Wang H. B., Wang P. Y., Wang X., Wan Y. L., Liu Y. C. Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription. Digestive Diseases and Sciences . 2012;57(12):3126–3135. doi: 10.1007/s10620-012-2259-4.
    1. Cani P. D., Bibiloni R., Knauf C., et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes . 2008;57(6):1470–1481. doi: 10.2337/db07-1403.
    1. Tolhurst G., Heffron H., Lam Y. S., et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes . 2012;61(2):364–371. doi: 10.2337/db11-1019.
    1. Paassen N. B.-v., Vincent A., Puiman P. J., et al. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. The Biochemical Journal . 2009;420(2):211–219. doi: 10.1042/BJ20082222.
    1. Sayin S. I., Wahlström A., Felin J., et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metabolism . 2013;17(2):225–235. doi: 10.1016/j.cmet.2013.01.003.
    1. Gai Z., Visentin M., Gui T., et al. Effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-kB signaling, and hepatic inflammation. Molecular Pharmacology . 2018;94(2):802–811. doi: 10.1124/mol.117.111047.
    1. Pickard J. M., Zeng M. Y., Caruso R., Nunez G. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunological Reviews . 2017;279(1):70–89. doi: 10.1111/imr.12567.
    1. Ridlon J. M., Kang D. J., Hylemon P. B. Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research . 2006;47(2):241–259. doi: 10.1194/jlr.R500013-JLR200.
    1. Buffie C. G., Bucci V., Stein R. R., et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature . 2015;517(7533):205–208. doi: 10.1038/nature13828.
    1. Inagaki T., Moschetta A., Lee Y. K., et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proceedings of the National Academy of Sciences of the United States of America . 2006;103(10):3920–3925. doi: 10.1073/pnas.0509592103.
    1. Song X., Sun X., Oh S. F., et al. Microbial bile acid metabolites modulate gut RORγ(+) regulatory T cell homeostasis. Nature . 2020;577(7790):410–415. doi: 10.1038/s41586-019-1865-0.
    1. Jia W., Xie G., Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nature Reviews. Gastroenterology & Hepatology . 2018;15(2):111–128. doi: 10.1038/nrgastro.2017.119.
    1. Lajczak-McGinley N. K., Porru E., Fallon C. M., et al. The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis. Physiological Reports . 2020;8(12, article e14456) doi: 10.14814/phy2.14456.
    1. Yang H., Zhou H., Zhuang L., et al. Plasma membrane-bound G protein-coupled bile acid receptor attenuates liver ischemia/reperfusion injury via the inhibition of toll-like receptor 4 signaling in mice. Liver Transplantation . 2017;23(1):63–74. doi: 10.1002/lt.24628.
    1. Igarashi K., Kashiwagi K. Modulation of cellular function by polyamines. The International Journal of Biochemistry & Cell Biology . 2010;42(1):39–51. doi: 10.1016/j.biocel.2009.07.009.
    1. Ramos-Molina B., Queipo-Ortuño M. I., Lambertos A., Tinahones F. J., Peñafiel R. Dietary and gut microbiota polyamines in obesity- and age-related diseases. Frontiers in Nutrition . 2019;6:p. 24. doi: 10.3389/fnut.2019.00024.
    1. Di Martino M. L., Campilongo R., Casalino M., Micheli G., Colonna B., Prosseda G. Polyamines: emerging players in bacteria-host interactions. International Journal of Medical Microbiology . 2013;303(8):484–491. doi: 10.1016/j.ijmm.2013.06.008.
    1. Igarashi K., Kashiwagi K. Characteristics of cellular polyamine transport in prokaryotes and eukaryotes. Plant Physiology and Biochemistry . 2010;48(7):506–512. doi: 10.1016/j.plaphy.2010.01.017.
    1. Sansonetti P. J. Shigellosis: an old disease in new clothes? PLoS Medicine . 2006;3(9, article e354) doi: 10.1371/journal.pmed.0030354.
    1. Kibe R., Kurihara S., Sakai Y., et al. Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Scientific Reports . 2015;4(1) doi: 10.1038/srep04548.
    1. Nakamura A., Ooga T., Matsumoto M. Intestinal luminal putrescine is produced by collective biosynthetic pathways of the commensal microbiome. Gut Microbes . 2019;10(2):159–171. doi: 10.1080/19490976.2018.1494466.
    1. Timmons J., Chang E. T., Wang J. Y., Rao J. N. Polyamines and gut mucosal homeostasis. J Gastrointest Dig Syst . 2013;2
    1. Yu T. X., Wang P. Y., Rao J. N., et al. Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function. Nucleic Acids Research . 2011;39(19):8472–8487. doi: 10.1093/nar/gkr567.
    1. Liu L., Guo X., Rao J. N., et al. Polyamines regulate E-cadherin transcription through c-Myc modulating intestinal epithelial barrier function. American Journal of Physiology. Cell Physiology . 2009;296(4):C801–C810. doi: 10.1152/ajpcell.00620.2008.
    1. Biczó G., Hegyi P., Sinervirta R., et al. Characterization of polyamine homeostasis in l-ornithine-induced acute pancreatitis in rats. Pancreas . 2010;39(7):1047–1056. doi: 10.1097/MPA.0b013e3181d3cdf0.
    1. Postler T. S., Ghosh S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metabolism . 2017;26(1):110–130. doi: 10.1016/j.cmet.2017.05.008.
    1. Matsumoto M., Kurihara S., Kibe R., Ashida H., Benno Y. Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PLoS One . 2011;6(8, article e23652) doi: 10.1371/journal.pone.0023652.
    1. Zelante T., Iannitti R. G., Cunha C., et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity . 2013;39(2):372–385. doi: 10.1016/j.immuni.2013.08.003.
    1. Thorburn A. N., Macia L., Mackay C. R. Diet, metabolites, and "western-lifestyle" inflammatory diseases. Immunity . 2014;40(6):833–842. doi: 10.1016/j.immuni.2014.05.014.
    1. Venkatesh M., Mukherjee S., Wang H., et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity . 2014;41(2):296–310. doi: 10.1016/j.immuni.2014.06.014.
    1. Lamas B., Richard M. L., Leducq V., et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nature Medicine . 2016;22(6):598–605. doi: 10.1038/nm.4102.
    1. Shimada Y., Kinoshita M., Harada K., et al. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS One . 2013;8(11, article e80604) doi: 10.1371/journal.pone.0080604.
    1. Haase S., Haghikia A., Wilck N., Muller D. N., Linker R. A. Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology . 2018;154(2):230–238. doi: 10.1111/imm.12933.
    1. Wlodarska M., Luo C., Kolde R., et al. Indoleacrylic Acid Produced by Commensal _Peptostreptococcus_ Species Suppresses Inflammation. Cell Host Microbe . 2017;22(1):25–37.e6. doi: 10.1016/j.chom.2017.06.007.
    1. Bansal T., Alaniz R. C., Wood T. K., Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proceedings of the National Academy of Sciences of the United States of America . 2010;107(1):228–233. doi: 10.1073/pnas.0906112107.
    1. Wilck N., Matus M. G., Kearney S. M., et al. Salt-responsive gut commensal modulates T (H)17 axis and disease. Nature . 2017;551(7682):585–589. doi: 10.1038/nature24628.
    1. Noack M., Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmunity Reviews . 2014;13(6):668–677. doi: 10.1016/j.autrev.2013.12.004.
    1. Williams B. B., Van Benschoten A. H., Cimermancic P., et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host & Microbe . 2014;16(4):495–503. doi: 10.1016/j.chom.2014.09.001.
    1. Mawe G. M., Hoffman J. M. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nature Reviews. Gastroenterology & Hepatology . 2013;10(8):473–486. doi: 10.1038/nrgastro.2013.105.
    1. Lee D. K., Jang S., Kim M. J., et al. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines. BMC Cancer . 2008;8(1):p. 310. doi: 10.1186/1471-2407-8-310.
    1. Hidalgo-Cantabrana C., Delgado S., Ruiz L., Ruas-Madiedo P., Sánchez B., Margolles A. Bifidobacteria and Their Health-Promoting Effects. Microbiology Spectrum . 2017;5(3) doi: 10.1128/microbiolspec.BAD-0010-2016.
    1. Castro-Bravo N., Wells J. M., Margolles A., Ruas-Madiedo P. Interactions of surface exopolysaccharides from Bifidobacterium and Lactobacillus within the intestinal environment. Frontiers in Microbiology . 2018;9:p. 2426. doi: 10.3389/fmicb.2018.02426.
    1. Bauerl C., Perez-Martinez G., Yan F., Polk D. B., Monedero V. Functional analysis of the p40 and p75 proteins from Lactobacillus casei BL23. Journal of Molecular Microbiology and Biotechnology . 2011;19(4):231–241. doi: 10.1159/000322233.
    1. Singh R., Chandrashekharappa S., Bodduluri S. R., et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nature Communications . 2019;10(1):p. 89. doi: 10.1038/s41467-018-07859-7.

Source: PubMed

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