Skip to main content
Log in

Probiotic treatment induced change of inflammation related metabolites in IBS-D patients/double-blind, randomized, placebo-controlled trial

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

There have been many studies suggesting that probiotics are effective in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). However, its mechanism of action as well as prediction of response is still to be elucidated. In the present study, to find out metabolomic characteristics of probiotic effect in IBS-D, we compared IBS symptom changes and metabolomic characteristics in the subjects’ urine samples between multi-strain probiotics (one strain of Lactobacillus sp. and four strains of Bifidobacterium sp.) group (n = 32) and placebo group (n = 31). After 8 weeks’ administration (3 times/day), dissatisfaction in bowel habits and stool frequencies were significantly improved. Also, probiotics group had significantly changed seven metabolites including palmitic acid methyl ester (PAME) and 4,6-dihydroxyquinoline, 4-(2-aminophenyl)-2,4-dioxobutanoic acid (DOBA). According to IBS-SSS and IBS-QoL questionnaires, IBS-SSS responders showed higher PAME levels and IBS-QoL responders showed lower DOBA levels. This suggests potential role of these metabolites as a biomarker to predict probiotics effect in IBS-D patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Barbara G, Cremon C, Pallotti F, De Giorgio R, Stanghellini V, Corinaldesi R. Postinfectious irritable bowel syndrome. J. Pediatr. Gastroenterol. Nutr. 48: S95-S97 (2009)

    CAS  PubMed  Google Scholar 

  • Barbara G, Cremon C. Serine proteases: new players in diarrhea-predominant irritable bowel syndrome. Gut. 57: 1035-1037 (2008)

    PubMed  Google Scholar 

  • Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 126: 693-702 (2004)

    PubMed  Google Scholar 

  • Bertini I, Calalbro A, De Carli V, Luchinat C, Nepi S, Porfirio B, Renzi D, Saccenti E, Tenori L. The metabonomic signature of celiac disease. J. Proteome. Res. 8: 170-177 (2009)

    CAS  PubMed  Google Scholar 

  • Brint EK, MacSharry J, Fanning A, Shanahan F, Quigley EM. Differential expression of toll-like receptors in patients with irritable bowel syndrome. Am. J. Gastroenterol. 106: 329-336 (2011)

    CAS  PubMed  Google Scholar 

  • Cai P, Kaphalia BS, Ansari GA. Methyl palmitate: inhibitor of phagocytosis in primary rat Kupffer cells. Toxicology. 210: 197-204 (2005)

    CAS  PubMed  Google Scholar 

  • Camilleri M. Current and future pharmacological treatments for diarrhea-predominant irritable bowel syndrome. Expert Opin. Pharmacother. 14: 1151-1160 (2013)

    CAS  PubMed  Google Scholar 

  • Cavigelli MA, Robertson GP, Klug MJ. Fatty acid methyl ester (FAME) profiles as measures of soil microbial community structure. Plant Soil. 170:99-113 (1995)

    CAS  Google Scholar 

  • Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 122: 1778-1783 (2002)

    PubMed  Google Scholar 

  • Crowell MD, Shetzline MA, Moses PL, Mawe GM, Talley NJ. Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function. Curr. Opin. Investig. Drugs. 5: 55-60 (2004)

    CAS  PubMed  Google Scholar 

  • Dabur R, Shirolkar A, Mishra V, Yadav BS. Non-invasive qualitative urinary metabolomic profiling discriminates gut microbiota derived metabolites in the moderate and chronic alcoholic cohort. Curr. Pharm. Biotechnol. 18: 1175-1189 (2017)

    CAS  PubMed  Google Scholar 

  • Dinan TG, Quigley EM, Ahmed SM, Scully P, O’Brien S, O’Mahony L, O’Mahony S, Shanahan F, Keeling PW. Hypothalamicpituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 130: 304-311 (2006)

    CAS  PubMed  Google Scholar 

  • Dunne C, Murphy L, Flynn S, O’Mahony L, O’Halloran S, Feeney M, Morrissey D, Thornton G, Fitzgerald G, Daly C, Kiely B, Quigley EM, O’Sullivan GC, Shanahan F, Collins JK. Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie. Van. Leeuwenhoek. 76: 279-292 (1999)

    CAS  PubMed  Google Scholar 

  • Ghoshal UC, Ranjan P. Post-infectious irritable bowel syndrome: the past, the present and the future. J. Gastroenterol. Hepatol. 26: 94-101 (2011)

    PubMed  Google Scholar 

  • Gwee KA, Lu CL, Ghoshal UC. Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed. J. Gastroenterol. Hepatol. 24: 1601-1607 (2009)

    PubMed  Google Scholar 

  • Hammerle CW, Surawicz CM. Updates on treatment of irritable bowel syndrome. World J. Gastroenterol. 14: 2639-2649 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Harper A, Naghibi MM, Garcha D. The role of bacteria, probiotics and diet in irritable bowel syndrome. Foods. 7: E13 (2018)

    PubMed  Google Scholar 

  • Hong KS, Kang HW, Im JP, Ji GE, Kim SG, Jung HC, Song IS, Kim JS. Effect of probiotics on symptoms in korean adults with irritable bowel syndrome. Gut Liver. 3:101-1077 (2009)

    PubMed  PubMed Central  Google Scholar 

  • Jeffery IB, Quigley EM, Öhman L, Simrén M, O’Toole PW. The microbiota link to irritable bowel syndrome: an emerging story. Gut Microbes. 3: 572-576 (2012)

    PubMed  PubMed Central  Google Scholar 

  • Keszthelyi D, Troost FJ, Masclee AA. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome. Am. J. Physiol. Gastrointest. Liver Physiol. 303: G141-G154 (2012)

    CAS  PubMed  Google Scholar 

  • Knights D, Lassen KG, Xavier RJ. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut. 62: 1505-1510 (2013)

    CAS  PubMed  Google Scholar 

  • Lee JY, Sohn KH, Rhee SH, Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 276: 16683-16689 (2001)

    CAS  PubMed  Google Scholar 

  • Malagelada JR, Malagelada C. Mechanism-oriented therapy of irritable bowel syndrome. Adv. Ther.33: 877-893 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marchesi JR, Holmes E, Khan F, Kochhar S, Scanlan P, Shanahan F, Wilson ID, Wang Y. Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J. Protrome Res. 6: 546-551 (2007)

    CAS  Google Scholar 

  • Marcobal A, Kashyap PC, Nelson TA, Aronov PA, Donia MS, Spormann A, Fischbach MA, Sonnenburg JL. A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. ISME J. 7: 1933-1943 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  • McCarthy J, O’Mahony L, O’Callaghan L, Sheil B, Vaughan EE, Fitzsimons N, Fitzgibbon J, O’Sullivan GC, Kiely B, Collins JK, Shanahan F. Double-blind, placebo-controlled trial of two probiotics strains in interleukin 10 knockout mice and mechanistic link with cytokine balance. Gut. 52: 975-980 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Hara AM. Shanahan F. Gut microbiota: mining for therapeutic potential. Clin. Gastroenterol. Hepatol. 5: 274-284 (2007)

    PubMed  Google Scholar 

  • O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O’Sullivan GC, Kiely B, Collins JK, Shanahan F, Quigley EM. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 128: 541-551 (2005)

    PubMed  Google Scholar 

  • O’Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O’Morain CA. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol. Motil. 12: 449-457 (2000)

    PubMed  Google Scholar 

  • Piche T, Saint-Paul MC, Dainese R, Marine-Barjoan E, Iannelli A, Montoya ML, Peyron JF, Czerucka D, Cherikh F, Filippi J, Tran A, Hébuterne X. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 57: 468-473 (2008)

    CAS  PubMed  Google Scholar 

  • Quigley EM. Bugs on the brain; brain in the gut-seeking explanations for common gastrointestinal symptoms. Ir. J. Med. Sci.182: 1-6 (2012)

    PubMed  Google Scholar 

  • Quigley EM, Craig OF. Irritable bowel syndrome; update on pathophysiology and management. Turk. J. Gastroenterol. 23: 313-322 (2012)

    PubMed  Google Scholar 

  • Schlüssel E, Preibisch G, Pütter S, Elstner EF. Homocysteine-induced oxidative damage: mechanisms and possible roles in neurodegenerative and atherogenic processes. Z. Naturforsch. C. 50: 699-707 (1995)

    PubMed  Google Scholar 

  • Scully P, McKernan DP, Keohane J, Groeger D, Shanahan F, Dinan TG, Quigley EM. Plasma cytokine profiles in females with irritable bowel syndrome and extra-intestinal co-morbidity. Am. J. Gastroenterol. 105: 2235-2243 (2010)

    CAS  PubMed  Google Scholar 

  • Spiller RC. Irritable bowel syndrome. Br. Med. Bull. 72: 15-29 (2004)

    PubMed  Google Scholar 

  • Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, Neal KR. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in postdysenteric irritable bowel syndrome. Gut. 47: 804-811 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Syed SK, Bui HH, Beavers LS, Farb TB, Ficorilli J, Chesterfield AK, Kuo MS, Bokvist K, Barrett DG, Efanov AM. Regulation of GPR119 receptor activity with endocannabinoid-like lipids. Am. J. Physiol. Endocrinol. Metab. 303:E1469-78 (2012)

    CAS  PubMed  Google Scholar 

  • Tagesson C, Franzén L, Dahl G, Weström B. Lysophosphatidylcholine increases rat ileal permeability to macromolecules. Gut. 26: 369-77 (1985)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Talley NJ, Butterfield J. Mast cell infiltration and degranulation in colonic mucosa in the irritable bowel syndrome. Am. J. Gastroenterol. 91: 1675-1676 (1996)

    CAS  PubMed  Google Scholar 

  • US Department of Health and Human Services (2012), Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry irritable bowel syndrome—clinical evaluation of drugs for treatment. 2012.

  • Weston AP, Biddle WL, Bhatia PS, Miner PB Jr. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig. Dis. Sci. 38: 1590-1595 (1993)

    CAS  PubMed  Google Scholar 

  • William HRT, Holmes E, Khan F, North BV, Patel VM, Marshall SE, Jewell DP, Ghosh S, Thomas HJ, Teare JP, Jakobovits S, Zeki S, Welsh KI, Taylor-Robinson SD, Orchard TR. Characterization of inflammatory bowel disease with urinary metabolic profiling. Am. J. Gastroenterol. 104: 1435-1444 (2009)

    Google Scholar 

  • Yu LM, Zhao KJ, Wang SS, Wang X, Lu B. Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome. World J. Gastroenterol. 24: 894-904 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Choi FF, Zhou Y, Leung FP, Tan S, Lin S, Xu H, Jia W, Sung JJ, Cai Z, Bian Z. Metabolite profiling of plasma and urine from rats with TNBS-induced acute colitis using UPLC-ESI-QTOF-MS-based metabonomics—a pilot study. FEBS J. 279: 2322-2338 (2012)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by research fund from the Clinical Research Institute of the Seoul National University Hospital. This work was also carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01123002)”, Rural Development Administration, Republic of Korea.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyoung Sup Hong.

Ethics declarations

Conflict of interest

The authors have no financial conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 245 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J., Cho, K., Kim, J.S. et al. Probiotic treatment induced change of inflammation related metabolites in IBS-D patients/double-blind, randomized, placebo-controlled trial. Food Sci Biotechnol 29, 837–844 (2020). https://doi.org/10.1007/s10068-019-00717-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-019-00717-2

Keywords

Navigation