Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2754–2764 | Cite as

Probiotics Ameliorate Stool Consistency in Patients with Chronic Constipation: A Randomized, Double-Blind, Placebo-Controlled Study

  • Jin Young Yoon
  • Jae Myung ChaEmail author
  • Ju Kyoung Oh
  • Pei Lei Tan
  • Sae Hun KimEmail author
  • Min Seob Kwak
  • Jung Won Jeon
  • Hyun Phil Shin
Original Article



The efficacy of probiotics for improving clinical symptoms, altering the fecal microbiota, and regulating serum immune cytokine levels was investigated in patients with irritable bowel syndrome-constipation (IBS-C) or functional constipation (FC).


A randomized, double-blind, placebo-controlled trial was conducted at Kyung Hee University Hospital between October 2016 and February 2017. Consecutive 18–75-year-old patients with diagnosis of IBS-C or FC (based on Rome IV criteria) consumed probiotics (3.0 × 108 CFU/g Streptococcus thermophilus MG510 and 1.0 × 108 CFU/g Lactobacillus plantarum LRCC5193) or a placebo daily for 4 weeks (weeks 1–4) and were followed up for a 4-week washout period without intervention (weeks 5–8). The primary outcomes of the study were Bristol Stool Form Scale and Complete Spontaneous Bowel Movements (CSBM). Efficacy was assessed by per protocol.


Stool consistency measured by the Bristol Stool Form Scale was significantly better in the probiotic group (n = 88) than in the placebo group (n = 83) at 4 and 8 weeks (3.7 ± 1.1 vs. 3.1 ± 1.1 at 8 weeks, P = 0.002). No significant difference was found in CSBM. The quality of life was significantly better in the probiotic group than in the placebo group at 4 weeks (P = 0.044) and 8 weeks (P = 0.049). The relative abundance of L. plantarum among the fecal microbiomes was significantly greater in the probiotic group than in the placebo group at 4 weeks (P = 0.029). However, the levels of other microbiomes and of serum cytokines (IL-10/IL-12 ratio and TNF-α) did not differ significantly between the two groups.


Probiotics significantly ameliorated stool consistency in patients with chronic constipation. In addition, the beneficial effect of L. plantarum on stool consistency remained after the probiotic supplementation was discontinued. The mechanism whereby probiotics benefit patients with chronic constipation should be clarified in further studies.


Probiotics Irritable bowel syndrome Constipation Lactobacillus plantarum 



This study was financially supported by Lotte Confectionery Co., Ltd, Korea.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Singh G, Lingala V, Wang H, et al. Use of health care resources and cost of care for adults with constipation. Clin Gastroenterol Hepatol. 2007;5:1053–1058.CrossRefPubMedGoogle Scholar
  2. 2.
    Ford AC, Quigley EM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1547–1561.CrossRefPubMedGoogle Scholar
  3. 3.
    Mearin F, Lacy BE, Chang Let al. Bowel disorders. Gastroenterology. Epub. 02/18/2016.Google Scholar
  4. 4.
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.CrossRefPubMedGoogle Scholar
  5. 5.
    Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007;25:599–608.CrossRefPubMedGoogle Scholar
  6. 6.
    Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133:24–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Attaluri A, Jackson M, Valestin J, Rao SS. Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am J Gastroenterol. 2010;105:1407–1411.CrossRefPubMedGoogle Scholar
  8. 8.
    O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–551.CrossRefPubMedGoogle Scholar
  9. 9.
    Begtrup LM, de Muckadell OB, Kjeldsen J, Christensen RD, Jarbol DE. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome—a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol. 2013;48:1127–1135.CrossRefPubMedGoogle Scholar
  10. 10.
    Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ. A randomized, double-blind, placebo-controlled multicenter trial of saccharomyces boulardii in irritable bowel syndrome: effect on quality of life. J Clin Gastroenterol. 2011;45:679–683.CrossRefPubMedGoogle Scholar
  11. 11.
    Cui S, Hu Y. Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Int J Clin Exp Med. 2012;5:238–244.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Guglielmetti S, Mora D, Gschwender M, Popp K. Randomised clinical trial: bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:1123–1132.CrossRefPubMedGoogle Scholar
  13. 13.
    Hong KS, Kang HW, Im JP, et al. Effect of probiotics on symptoms in Korean adults with irritable bowel syndrome. Gut Liver. 2009;3:101–107.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Simren M, Ohman L, Olsson J, et al. Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome—a randomized, double-blind, controlled study. Aliment Pharmacol Ther. 2010;31:218–227.CrossRefPubMedGoogle Scholar
  15. 15.
    Sondergaard B, Olsson J, Ohlson K, Svensson U, Bytzer P, Ekesbo R. Effects of probiotic fermented milk on symptoms and intestinal flora in patients with irritable bowel syndrome: a randomized, placebo-controlled trial. Scand J Gastroenterol. 2011;46:663–672.CrossRefPubMedGoogle Scholar
  16. 16.
    Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:1581–1590.CrossRefPubMedGoogle Scholar
  17. 17.
    Williams EA, Stimpson J, Wang D, et al. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2009;29:97–103.CrossRefPubMedGoogle Scholar
  18. 18.
    Enck P, Junne F, Klosterhalfen S, Zipfel S, Martens U. Therapy options in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2010;22:1402–1411.PubMedGoogle Scholar
  19. 19.
    Possemiers S, Marzorati M, Verstraete W, Van de Wiele T. Bacteria and chocolate: a successful combination for probiotic delivery. Int J Food Microbiol. 2010;141:97–103.CrossRefPubMedGoogle Scholar
  20. 20.
    Videlock EJ, Cheng V, Cremonini F. Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1084–1092.CrossRefPubMedGoogle Scholar
  21. 21.
    Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome global improvement scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003;48:1317–1323.CrossRefPubMedGoogle Scholar
  22. 22.
    Wiklund IK, Fullerton S, Hawkey CJ, et al. An irritable bowel syndrome-specific symptom questionnaire: development and validation. Scand J Gastroenterol. 2003;38:947–954.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee EH, Kwon O, Hahm KB, et al. Irritable bowel syndrome-specific health-related quality of life instrument: development and psychometric evaluation. Health Qual Life Outcomes. 2016;14:22.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Drossman D, Morris CB, Hu Y, et al. Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment. Am J Gastroenterol. 2007;102:1442–1453.CrossRefPubMedGoogle Scholar
  25. 25.
    Solem CT, Patel H, Mehta S, Mody R, Macahilig C, Gao X. Treatment patterns, symptom reduction, quality of life, and resource use associated with lubiprostone in irritable bowel syndrome constipation subtype. Curr Med Res Opin. 2016;32:899–905.CrossRefPubMedGoogle Scholar
  26. 26.
    Lee J, Rheem S, Yun B, et al. Effects of probiotic yoghurt on symptoms and intestinal microbiota in patients with irritable bowel syndrome. Int J Diary Technol. 2013;66:243–255.CrossRefGoogle Scholar
  27. 27.
    Design of Treatment Trials C, Irvine EJ, Whitehead WE, et al. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2006;130:1538–1551.CrossRefGoogle Scholar
  28. 28.
    Shekhar C, Monaghan PJ, Morris J, et al. Rome III functional constipation and irritable bowel syndrome with constipation are similar disorders within a spectrum of sensitization, regulated by serotonin. Gastroenterology. 2013;145:749–757.CrossRefPubMedGoogle Scholar
  29. 29.
    Wong RK, Palsson OS, Turner MJ, et al. Inability of the Rome III criteria to distinguish functional constipation from constipation-subtype irritable bowel syndrome. Am J Gastroenterol. 2010;105:2228–2234.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Schmulson MJ, Drossman DA. What is new in Rome IV. J Neurogastroenterol Motil. 2017;23:151–163.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kashyap PC, Marcobal A, Ursell LK, et al. Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology. 2013;144:967–977.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62:159–176.CrossRefPubMedGoogle Scholar
  33. 33.
    Saad RJ, Rao SS, Koch KL, et al. Do stool form and frequency correlate with whole-gut and colonic transit? Results from a multicenter study in constipated individuals and healthy controls. Am J Gastroenterol. 2010;105:403–411.CrossRefPubMedGoogle Scholar
  34. 34.
    Cook SI, Sellin JH. Review article: short chain fatty acids in health and disease. Aliment Pharmacol Ther. 1998;12:499–507.CrossRefPubMedGoogle Scholar
  35. 35.
    Johansson ML, Nobaek S, Berggren A, et al. Survival of Lactobacillus plantarum DSM 9843 (299v), and effect on the short-chain fatty acid content of faeces after ingestion of a rose-hip drink with fermented oats. Int J Food Microbiol. 1998;42:29–38.CrossRefPubMedGoogle Scholar
  36. 36.
    Alander M, Satokari R, Korpela R, et al. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl Environ Microbiol. 1999;65:351–354.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Zoetendal EG, von Wright A, Vilpponen-Salmela T, Ben-Amor K, Akkermans AD, de Vos WM. Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces. Appl Environ Microbiol. 2002;68:3401–3407.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Yoon H, Park YS, Lee DH, Seo JG, Shin CM, Kim N. Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Biochem Nutr. 2015;57:129–134.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Collins JK, Dunne C, Murphy L, et al. A randomised controlled trial of a probiotic Lactobacillus strain in healthy adults: assessment of its delivery, transit, and influence on microbial flora and enteric immunity. Microb Ecol Health Dis. 2002;14:81–89.CrossRefGoogle Scholar
  40. 40.
    Johansson ML, Molin G, Jeppsson B, Nobaek S, Ahrne S, Bengmark S. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environ Microbiol. 1993;59:15–20.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Stevenson C, Blaauw R, Fredericks E, Visser J, Roux S. Randomized clinical trial: effect of Lactobacillus plantarum 299 v on symptoms of irritable bowel syndrome. Nutrition. 2014;30:1151–1157.CrossRefPubMedGoogle Scholar
  42. 42.
    Enck P, Zimmermann K, Menke G, Muller-Lissner S, Martens U, Klosterhalfen S. A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome—a randomized controlled trial with primary care physicians. Neurogastroenterol Motil. 2008;20:1103–1109.CrossRefPubMedGoogle Scholar
  43. 43.
    Enck P, Zimmermann K, Menke G, Klosterhalfen S. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009;47:209–214.CrossRefPubMedGoogle Scholar
  44. 44.
    Roberts LM, McCahon D, Holder R, Wilson S, Hobbs FD. A randomised controlled trial of a probiotic ‘functional food’ in the management of irritable bowel syndrome. BMC Gastroenterol. 2013;13:45.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Pathmakanthan S, Li CK, Cowie J, Hawkey CJ. Lactobacillus plantarum 299: beneficial in vitro immunomodulation in cells extracted from inflamed human colon. J Gastroenterol Hepatol. 2004;19:166–173.CrossRefPubMedGoogle Scholar
  46. 46.
    Bashashati M, Rezaei N, Shafieyoun A, et al. Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil. 2014;26:1036–1048.CrossRefPubMedGoogle Scholar
  47. 47.
    Pinto-Sanchez MI, Hall GB, Ghajar K, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153:448–459.CrossRefPubMedGoogle Scholar
  48. 48.
    Reichardt N, Duncan SH, Young P, et al. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014;8:1323–1335.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ramos-Romero S, Hereu M, Molinar-Toribio E, et al. Effects of the combination of omega-3 PUFAs and proanthocyanidins on the gut microbiota of healthy rats. Food Res Int. 2017;97:364–371.CrossRefPubMedGoogle Scholar
  50. 50.
    Haarman M, Knol J. Quantitative real-time PCR analysis of fecal Lactobacillus species in infants receiving a prebiotic infant formula. Appl Environ Microbiol. 2006;72:2359–2365.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Song Y, Kato N, Liu C, Matsumiya Y, Kato H, Watanabe K. Rapid identification of 11 human intestinal Lactobacillus species by multiplex PCR assays using group- and species-specific primers derived from the 16S-23S rRNA intergenic spacer region and its flanking 23S rRNA. FEMS Microbiol Lett. 2000;187:167–173.PubMedGoogle Scholar
  52. 52.
    Calles-Enriquez M, Eriksen BH, Andersen PS, et al. Sequencing and transcriptional analysis of the Streptococcus thermophilus histamine biosynthesis gene cluster: factors that affect differential hdcA expression. Appl Environ Microbiol. 2010;76:6231–6238.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Requena T, Burton J, Matsuki T, et al. Identification, detection, and enumeration of human bifidobacterium species by PCR targeting the transaldolase gene. Appl Environ Microbiol. 2002;68:2420–2427.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Guo X, Xia X, Tang R, Wang K. Real-time PCR quantification of the predominant bacterial divisions in the distal gut of Meishan and Landrace pigs. Anaerobe. 2008;14:224–228.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jin Young Yoon
    • 1
  • Jae Myung Cha
    • 1
    Email author
  • Ju Kyoung Oh
    • 2
  • Pei Lei Tan
    • 2
  • Sae Hun Kim
    • 2
    Email author
  • Min Seob Kwak
    • 1
  • Jung Won Jeon
    • 1
  • Hyun Phil Shin
    • 1
  1. 1.Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University Hospital at GangdongKyung Hee University School of MedicineSeoulRepublic of Korea
  2. 2.Department of Food Bioscience and Technology, College of Life Science and BiotechnologyKorea UniversitySeoulRepublic of Korea

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