Journal Home Online First Current Issue Archive For Authors Journal Information 中文版

Engineering >> 2021, Volume 7, Issue 3 doi: 10.1016/j.eng.2020.06.026

Lactobacillus plantarum CCFM8610 Alleviates Irritable Bowel Syndrome and Prevents Gut Microbiota Dysbiosis: A Randomized, Double-blind, Placebo-controlled, Pilot Clinical Trial

a State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
b School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
c Hwa Chong Institution (College), Singapore 269734, Singapore
d International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122 China
e National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
f Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China
g (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
h The Tinghu People's Hospital, Yancheng 224002, China
i Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China

Received: 2020-04-09 Revised: 2020-05-17 Accepted: 2020-06-18 Available online: 2020-12-24

Next Previous

Abstract

Irritable bowel syndrome with diarrhea (IBS-D) is chronic intestinal dysfunction with diarrhea and other complicated clinical symptoms, and it has a great impact on the daily life and mental state of patients. Some studies have reported that ingestion of probiotics can significantly alleviate a variety of intestinal diseases. The purpose of this study was to investigate the IBS-D-alleviating effects of a probiotic strain, Lactobacillus plantarum CCFM8610, with multiple health-promoting effects. The study was a 12-week, randomized, double-blind, placebo-controlled, pilot clinical trial. Seventy-five patients were randomly assigned to receive the placebo, oligosaccharides, or L. plantarum CCFM8610 (1 × 1010 colony-forming units (CFU) per day), with a 2-week run-in period, an 8-week intervention period, and a 2-week follow-up observation period. The patients' clinical symptoms and quality of life were examined by the IBS symptom severity scale (IBS-SSS) and the IBS quality of life scale (IBS-QOL). Changes in gut microbiota composition and diversity were measured at the end of the intervention period. The oral administration of L. plantarum CCFM8610 significantly decreased the IBS-SSS and IBS-QOL scores, reduced IBS-D symptom severity, recovered gut microbiota diversity, decreased the relative abundance of bloating-related genus Methanobrevibacter, and increased the relative abundance of butyric acid-producing genera, including Anaerostipes, Anaerotruncus, Bifidobacterium, Butyricimonas, and Odoribacter. These findings suggest that ingestion of L. plantarum CCFM8610 can significantly alleviate clinical symptoms and gut microbiota dysbiosis in IBS-D patients. The IBS-D-alleviating effect of L. plantarum CCFM8610 may be related to the increase in the relative abundance of butyric acid-producing genera in the intestine.

Figures

Fig. 1

Fig. 2

Fig. 3

Fig. 4

References

[ 1 ] Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol 2016;1(2):133–46. link1

[ 2 ] Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 2012;10(7):712–21. link1

[ 3 ] Shin A, Ballou S, Camilleri M, Xu H, Lembo A. Information- and health-care seeking behaviors in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. In press.

[ 4 ] Longo DL, Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med 2017;376(26):2566–78. link1

[ 5 ] Singh P, Staller K, Barshop K, Dai E, Newman J, Yoon S, et al. Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation. World J Gastroenterol 2015;21 (26):8103–9. link1

[ 6 ] Lin S, Mooney PD, Kurien M, Aziz I, Leeds JS, Sanders DS. Prevalence, investigational pathways and diagnostic outcomes in differing irritable bowel syndrome subtypes. Eur J Gastroenterol Hepatol 2014;26(10):1176–80. link1

[ 7 ] Ding Y. Sustainable management and action in China under the increasing risks of global climate change. Engineering 2018;4(3):301–5. link1

[ 8 ] Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 2019;6(3):211–24. link1

[ 9 ] Grabauskas G, Wu X, Gao J, Li JY, Turgeon DK, Owyang C. Prostaglandin E2, produced by mast cells in colon tissues from patients with irritable bowel syndrome, contributes to visceral hypersensitivity in mice. Gastroenterology 2020;158(8):2195–207.e6. link1

[10] Coëffier M, Gloro R, Boukhettala N, Aziz M, Lecleire S, Vandaele N, et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010;105(5):1181–8. link1

[11] Rajilic´ -Stojanovic´ M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011;141 (5):1792–801. link1

[12] Liu Y, Zhang L, Wang X, Wang Z, Zhang J, Jiang R, et al. Similar fecal microbiota signatures in patients with diarrhea-predominant irritable bowel syndrome and patients with depression. Clin Gastroenterol Hepatol 2016;14 (11):1602–11. link1

[13] Özogul F, Hamed I. The importance of lactic acid bacteria for the prevention of bacterial growth and their biogenic amines formation: a review. Crit Rev Food Sci Nutr 2018;58(10):1660–70. link1

[14] Natividad JM, Lamas B, Pham HP, Michel ML, Rainteau D, Bridonneau C, et al. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nat Commun 2018;9(1):1–15. link1

[15] Kuhn KA, Schulz HM, Regner EH, Severs EL, Hendrickson JD, Mehta G, et al. Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity. Mucosal Immunol 2018;11(2):357–68. link1

[16] Fukui H, Oshima T, Tanaka Y, Oikawa Y, Makizaki Y, Ohno H, et al. Effect of probiotic Bifidobacterium bifidum G9-1 on the relationship between gut microbiota profile and stress sensitivity in maternally separated rats. Sci Rep 2018;8(1):12384. link1

[17] Lu YM, Xie JJ, Peng CG, Wang BH, Wang KC, Li LJ. Enhancing clinical efficacy through the gut microbiota: a new field of traditional Chinese medicine. Engineering 2019;5(1):40–9. link1

[18] Sun YY, Li M, Li YY, Li LX, Zhai WZ, Wang P, et al. The effect of Clostridium butyricum on symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. Sci Rep 2018;8(1):2964. link1

[19] Andresen V, Gschossmann J, Layer P. Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Lancet Gastroenterol Hepatol 2020;5(7):658–66. link1

[20] Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, 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(2):448–59. link1

[21] Martoni CJ, Srivastava S, Leyer GJ. Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12 improve abdominal pain severity and symptomology in irritable bowel syndrome: randomized controlled trial. Nutrients 2020;12(2):363. link1

[22] Liu Y, Sheng Y, Pan Q, Xue Y, Yu L, Tian F, et al. Identification of the key physiological characteristics of Lactobacillus plantarum strains for ulcerative colitis alleviation. Food Funct 2020;11(2):1279–91. link1

[23] Zhai Q, Gong X, Wang C, Zhao J, Zhang H, Tian F, et al. Food-borne patulin toxicity is related to gut barrier disruption and can be prevented by docosahexaenoic acid and probiotic supplementation. Food Funct 2019;10 (3):1330–9. link1

[24] Fang Z, Lu W, Zhao J, Zhang H, Qian L, Wang Q, et al. Probiotics modulate the gut microbiota composition and immune responses in patients with atopic dermatitis: a pilot study. Eur J Nutr 2020;59:2119–30. link1

[25] Niv E, Naftali T, Hallak R, Vaisman N. The efficacy of Lactobacillus reuteri ATCC 55730 in the treatment of patients with irritable bowel syndrome—a double blind, placebo-controlled, randomized study. Clin Nutr 2005;24 (6):925–31. link1

[26] Wang L, Pan M, Li D, Yin Y, Jiang T, Fang S, et al. Metagenomic insights into the effects of oligosaccharides on the microbial composition of cecal contents in constipated mice. J Funct Foods 2017;38:486–96. link1

[27] Wu RY, Määttänen P, Napper S, Scruten E, Li B, Koike Y, et al. Non-digestible oligosaccharides directly regulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota. Microbiome 2017;5 (1):135. link1

[28] Liu Y, Gibson GR, Walton GE. An in vitro approach to study effects of prebiotics and probiotics on the faecal microbiota and selected immune parameters relevant to the elderly. PLoS ONE 2016;11(9):e0162604. link1

[29] Silk D, Davis A, Vulevic J, Tzortzis G, Gibson G. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2009;29(5):508–18. link1

[30] Wilson B, Rossi M, Dimidi E, Whelan K. Prebiotics in irritable bowel syndrome and other functional bowel disorders in adults: a systematic review and metaanalysis of randomized controlled trials. Am J Clin Nutr 2019;109 (4):1098–111. link1

[31] Buono JL, Carson RT, Flores NM. Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea. Health Qual Life Outcomes 2017;15(1):35. link1

[32] Brenner DM, Sayuk GS. Current US Food and Drug Administration-approved pharmacologic therapies for the treatment of irritable bowel syndrome with diarrhea. Adv Ther 2020;37(1):83–96. link1

[33] Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. J Neurogastroenterol 2016;22(4):558–74. link1

[34] Zielin´ ska A, Sałaga M, Włodarczyk M, Fichna J. Chronic abdominal pain in irritable bowel syndrome—current and future therapies. Expert Rev Clin Pharmacol 2018;11(7):729–39. link1

[35] Wang H, Gong J, Wang W, Long Y, Fu X, Fu Y, et al. Are there any different effects of Bifidobacterium, Lactobacillus and Streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model?. PLoS ONE 2014;9(3):e90153. link1

[36] Liu YW, Wang YP, Yen HF, Liu PY, Tzeng WJ, Tsai CF, et al. Lactobacillus plantarum PS128 ameliorated visceral hypersensitivity in rats through the gut–brain axis. Probiotics Antimicro 2020;12(3):980–93.

[37] Goebel-Stengel M, Stengel A, Schmidtmann M, Van Der Voort I, Kobelt P, Mönnikes H. Unclear abdominal discomfort: pivotal role of carbohydrate malabsorption. J Neurogastroenterol 2014;20(2):228–35. link1

[38] Zhang S, Xu Z, Qin L, Kong J. Low-sugar yogurt making by the co-cultivation of Lactobacillus plantarum WCFS1 with yogurt starter cultures. J Dairy Sci 2020;103(4):3045–54. link1

[39] Dimitrovski D, Velickova E, Dimitrovska M, Langerholc T, Winkelhausen E. Synbiotic functional drink from jerusalem artichoke juice fermented by probiotic Lactobacillus plantarum PCS26. J Food Sci Technol 2016;53 (1):766–74. link1

[40] Zhai Q, Wang G, Zhao J, Liu X, Tian F, Zhang H, et al. Protective effects of Lactobacillus plantarum CCFM8610 against acute cadmium toxicity in mice. Appl Environ Microbiol 2013;79(5):1508–15. link1

[41] Tavel ME. The placebo effect: the good, the bad, and the ugly. Am J Med 2014;127(6):484–8. link1

[42] Ballou S, McMahon C, Lee HN, Katon J, Shin A, Rangan V, et al. Effects of irritable bowel syndrome on daily activities vary among subtypes based on results from the IBS in America survey. Clin Gastroenterol Hepatol 2019;17 (12):2471–8. link1

[43] Cryan JF, O’Riordan KJ, Cowan CS, Sandhu KV, Bastiaanssen TF, Boehme M, et al. The microbiota–gut–brain axis. Physiol Rev 2019;99(4):1877–2013. link1

[44] Fond G, Loundou A, Hamdani N, Boukouaci W, Dargel A, Oliveira J, et al. Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci 2014;264(8):651–60. link1

[45] Turna J, Kaplan KG, Patterson B, Bercik P, Anglin R, Soreni N, et al. Higher prevalence of irritable bowel syndrome and greater gastrointestinal symptoms in obsessive-compulsive disorder. J Psychiatr Res 2019;118:1–6. link1

[46] Liu RT, Walsh RF, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev 2019;102:13–23. link1

[47] Gu Y, Zhou G, Huang S, Wang B, Cao H. The potential role of gut mycobiome in irritable bowel syndrome. Front Microbiol 2019;10:1894. link1

[48] Carroll IM, Ringel-Kulka T, Keku TO, Chang YH, Packey CD, Sartor RB, et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J PhysiolGastr Liver Physiol 2011;301(5):G799–807. link1

[49] De Palma G, Lynch MD, Lu J, Dang VT, Deng Y, Jury J, et al. Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Sci Transl Med 2017;9(379): eaaf6397. link1

[50] Chung CS, Chang PF, Liao CH, Lee TH, Chen Y, Lee YC, et al. Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects. Scand J Gastroenterol 2016;51(4):410–9. link1

[51] Nagel R, Traub RJ, Allcock RJ, Kwan MM, Bielefeldt-Ohmann H. Comparison of faecal microbiota in Blastocystis-positive and Blastocystis-negative irritable bowel syndrome patients. Microbiome 2016;4(1):47. link1

[52] Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology 2017;152(1):111–23. link1

[53] Seo M, Heo J, Yoon J, Kim SY, Kang YM, Yu J, et al. Methanobrevibacter attenuation via probiotic intervention reduces flatulence in adult human: a non-randomised paired-design clinical trial of efficacy. PLoS ONE 2017;12(9): e0184547. link1

[54] Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L. Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. Mol Cancer Res 2003;1(11):855–62. link1

[55] Fachi JL, de Souza FJ, Pral LP, da Silva BK, Corrêa RO, de Andrade MCP, et al. Butyrate protects mice from Clostridium difficile-induced colitis through an HIF-1-dependent mechanism. Cell Reports 2019;27(3):750–61. link1

[56] Krokowicz L, Kaczmarek BF, Krokowicz P, Stojcev Z, Mackiewicz J, Walkowiak J, et al. Sodium butyrate and short chain fatty acids in prevention of travellers’ diarrhoea: a randomized prospective study. Travel Med Infect Dis 2014;12 (2):183–8. link1

[57] Schroeder FA, Lin CL, Crusio WE, Akbarian S. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 2007;62(1):55–64. link1

[58] Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: the bread and butter of the microbiota– gut–brain axis? Neurochem Int 2016;99:110–32. link1

[59] Pozuelo M, Panda S, Santiago A, Mendez S, Accarino A, Santos J, et al. Reduction of butyrate- and methane-producing microorganisms in patients with irritable bowel syndrome. Sci Rep 2015;5(1):12693. link1

[60] Liu H, Wang J, He T, Becker S, Zhang G, Li D, et al. Butyrate: a double-edged sword for health? Adv Nutr 2018;9(1):21–9. link1

[61] Sloan TJ, Jalanka J, Major GA, Krishnasamy S, Pritchard S, Abdelrazig S, et al. A low FODMAP diet is associated with changes in the microbiota and reduction in breath hydrogen but not colonic volume in healthy subjects. PLoS ONE 2018;13(7):e0201410. link1

[62] Chang L, Chey WD, Harris L, Olden K, Surawicz C, Schoenfeld P. Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data. Am J Gastroenterol 2006;101(5):1069–79. link1

[63] Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 2016;374(3):242–53. link1

[64] Yelin I, Flett KB, Merakou C, Mehrotra P, Stam J, Snesrud E, et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat Med 2019;25(11):1728–32. link1

[65] Dauby N. Risks of Saccharomyces boulardii-containing probiotics for the prevention of Clostridium difficile infection in the elderly. Gastroenterology 2017;153(5):1450–1. link1

[66] Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis 2015;60 Suppl 2:S129–34. link1

[67] Costa RL, Moreira J, Lorenzo A, Lamas CC. Infectious complications following probiotic ingestion: a potentially underestimated problem? A systematic review of reports and case series. BMC Complement Altern Med 2018;18 (1):329. link1

[68] Rossi F, Amadoro C, Colavita G. Members of the Lactobacillus genus complex (LGC) as opportunistic pathogens: a review. Microorganisms 2019;7(5):126. link1

[69] Zhai Q, Liu Y, Wang C, Zhao J, Zhang H, Tian F, et al. Increased cadmium excretion due to oral administration of Lactobacillus plantarum strains by regulating enterohepatic circulation in mice. J Agric Food Chem 2019;67 (14):3956–65. link1

Related Research