Probiotics and Antimicrobial Proteins

, Volume 10, Issue 3, pp 466–477 | Cite as

A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

  • Matthew Corbitt
  • N. Campagnolo
  • D. Staines
  • S. Marshall-Gradisnik


Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use. Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms). The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.


Chronic fatigue syndrome Myalgic encephalomyelitis Gastrointestinal symptoms Irritable bowel symptoms Probiotics 



Gratitude is extended to Dr. Samantha Johnston for assistance with this manuscript.

Author Contributions

MC designed the study, search strategy, performed the searches and screenings, analysis, primary quality assessment, and wrote the draft and final manuscript. NC completed the secondary quality assessment and provided consultation on the writing of the manuscript. DS critically reviewed the drafts and provided input for the final manuscript. SMG supervised the study, critically reviewed the drafts and provided input for the final manuscript. MC, DS and SMG all critically reviewed the final version of the manuscript and approved it for publication.

Compliance with Ethical Standards

The lead author confirms that this manuscript is an accurate, honest and transparent account of the study undertaken and being reported, with no aspects being omitted and any discrepancies explained. The reporting of this work is compliant with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12602_2018_9397_MOESM1_ESM.docx (24 kb)
ESM 1 (DOCX 24 kb)


  1. 1.
    Campagnolo N, Johnston S, Collatz A, Staines D, Marshall-Gradisnik S (2017) Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet 30(3):247–259. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Carruthers BM, van de Sande MI, De Meirleir KL et al (2011) Myalgic encephalomyelitis: international consensus criteria: review: ME: Intl. Consensus criteria. J Intern Med 270(4):327–338. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Prins JB, van der Meer JW, Bleijenberg G (2006) Chronic fatigue syndrome. Lancet 367(9507):346–355. CrossRefPubMedGoogle Scholar
  4. 4.
    Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (1994) The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121(12):953–959. CrossRefPubMedGoogle Scholar
  5. 5.
    Johnston S, Brenu E, Staines D, Marshall-Gradisnik (2013) The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis. Clin Epidemiol:105.
  6. 6.
    Reynolds KJ, Vernon SD, Bouchery E, Reeves WC (2004) The economic impact of chronic fatigue syndrome. Cost Eff Resour Alloc 2(1):4. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S (1999) A community-based study of chronic fatigue syndrome. Arch Intern Med 159(18):2129–2137. CrossRefPubMedGoogle Scholar
  8. 8.
    Forsyth LM, Preuss HG, MacDowell AL et al (1999) Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 82(2):185–191. CrossRefPubMedGoogle Scholar
  9. 9.
    Collatz A, Johnston SC, Staines DR, Marshall-Gradisnik SM (2016) A systematic review of drug therapies for chronic fatigue syndrome/myalgic encephalomyelitis. Clin Ther 38(6):1263–1271.e9. CrossRefPubMedGoogle Scholar
  10. 10.
    Carruthers BM, Jain AK, De Meirleir KL et al (2003) Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr 11(1):7–115. CrossRefGoogle Scholar
  11. 11.
    Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC (2003) A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes 1(1):49. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Grant JE, Veldee MS, Buchwald D (1996) Analysis of dietary intake and selected nutrient concentrations in patients with chronic fatigue syndrome. J Am Diet Assoc 96(4):383–386. CrossRefPubMedGoogle Scholar
  13. 13.
    Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ (2004) The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria. Ann Epidemiol 14(2):95–100. CrossRefPubMedGoogle Scholar
  14. 14.
    Frémont M, Coomans D, Massart S, De Meirleir K (2013) High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients. Anaerobe 22:50–56. CrossRefPubMedGoogle Scholar
  15. 15.
    Aaron LA, Burke MM, Buchwald D (2000) Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med 160(2):221–227. CrossRefPubMedGoogle Scholar
  16. 16.
    Johnston SC, Staines DR, Marshall-Gradisnik SM (2016) Epidemiological characteristics of chronic fatigue syndrome/myalgic encephalomyelitis in Australian patients. Clin Epidemiol 8:97–107. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Jain AK, Carruthers BM, van de Sande MI, Barron SR, Donaldson CCS, Dunne JV, Gingrich E, Heffez DS, Leung FYK, Malone DG, Romano TJ, Russell IJ, Saul D, Seibel DG (2003) Fibromyalgia syndrome: Canadian clinical working case definition, diagnostic and treatment protocols—a consensus document. J Musculoskelet Pain 11(4):3–107. CrossRefGoogle Scholar
  18. 18.
    Abbas Z, Yakoob J, Jafri W, Ahmad Z, Azam Z, Usman MW, Shamim S, Islam M (2014) Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial. Eur J Gastroenterol Hepatol 26:630–639. CrossRefPubMedGoogle Scholar
  19. 19.
    Andriulli A, Neri M, Loguercio C, Terreni N, Merla A, Cardarella MP, Federico A, Chilovi F, Milandri GL, de Bona M, Cavenati S, Gullini S, Abbiati R, Garbagna N, Cerutti R, Grossi E (2008) Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in patients with irritable bowel syndrome: a multicenter, randomized study. J Clin Gastroenterol 42(Suppl 3 Pt 2):S218–S223. CrossRefPubMedGoogle Scholar
  20. 20.
    Begtrup LM, de Muckadell OBS, Kjeldsen J, Christensen RP, Jarbøl DE (2013) Long-term treatment with probiotics in primary care patients with irritable bowel syndrome—a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol 48(10):1127–1135. CrossRefPubMedGoogle Scholar
  21. 21.
    Cappello C, Tremolaterra F, Pascariello A, Ciacci C, Iovino P (2013) A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life. Int J Color Dis 28(3):349–358. CrossRefGoogle Scholar
  22. 22.
    Dapoigny M, Piche T, Ducrotte P, Lunaud B, Cardot JM, Bernalier-Donadille A (2012) Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study. World J Gastroenterol 18(17):2067–2075. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ducrotté P, Sawant P, Jayanthi V (2012) Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol 18(30):4012–4018. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Faghihi AH, Agah S, Masoudi M et al (2015) Efficacy of probiotic Escherichia coli Nissle 1917 in patients with irritable bowel syndrome: a double blind placebo-controlled randomized trial. Acta Medica Indones 47:201–208Google Scholar
  25. 25.
    Groeger D, O’Mahony L, Murphy EF, Bourke JF, Dinan TG, Kiely B, Shanahan F, Quigley EMM (2013) Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 4(4):325–339. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Guglielmetti S, Mora D, Gschwender M, Popp K (2011) 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 33(10):1123–1132. CrossRefPubMedGoogle Scholar
  27. 27.
    Guyonnet D, Chassany O, Ducrotte P et al (2007) Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment Pharmacol Ther 26(3):475–486. CrossRefPubMedGoogle Scholar
  28. 28.
    Kajander K, Hatakka K, Poussa T et al (2005) A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther 22(5):387–394. CrossRefPubMedGoogle Scholar
  29. 29.
    Kajander K, Myllyluoma E, Rajilić-Stojanović M et al (2008) Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther 27(1):48–57. CrossRefPubMedGoogle Scholar
  30. 30.
    Ki Cha B, Mun Jung S, Hwan Choi C, Song ID, Woong Lee H, Joon Kim H, Hyuk J, Kyung Chang S, Kim K, Chung WS, Seo JG (2012) The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol 46(3):220–227. CrossRefPubMedGoogle Scholar
  31. 31.
    Kim HJ, Camilleri M, McKinzie S et al (2003) A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 17(7):895–904. CrossRefPubMedGoogle Scholar
  32. 32.
    Kruis W, Chrubasik S, Boehm S, Stange C, Schulze J (2012) A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel syndrome. Int J Color Dis 27(4):467–474. CrossRefGoogle Scholar
  33. 33.
    Ligaarden SC, Axelsson L, Naterstad K, Lydersen S, Farup PG (2010) A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial. BMC Gastroenterol 10(1):16. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Majeed M, Nagabhushanam K, Natarajan S, Sivakumar A, Ali F, Pande A, Majeed S, Karri SK (2015) Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant irritable bowel syndrome: a double blind randomized placebo controlled pilot clinical study. Nutr J 15(1).
  35. 35.
    Mezzasalma V, Manfrini E, Ferri E, Sandionigi A, la Ferla B, Schiano I, Michelotti A, Nobile V, Labra M, di Gennaro P (2016) A randomized, double-blind, placebo-controlled trial: the efficacy of multispecies probiotic supplementation in alleviating symptoms of irritable bowel syndrome associated with constipation. Biomed Res Int 2016:4740907. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Pineton de Chambrun G, Neut C, Chau A, Cazaubiel M, Pelerin F, Justen P, Desreumaux P (2015) A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome. Dig Liver Dis 47(2):119–124. CrossRefPubMedGoogle Scholar
  37. 37.
    Ringel-Kulka T, Palsson OS, Maier D, Carroll I, Galanko JA, Leyer G, Ringel Y (2011) Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol 45(6):518–525. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Simrén M, Ohman L, Olsson J et al (2010) 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 31:218–227. CrossRefPubMedGoogle Scholar
  39. 39.
    Sisson G, Ayis S, Sherwood RA, Bjarnason I (2014) Randomised clinical trial: a liquid multi-strain probiotic vs. placebo in the irritable bowel syndrome—a 12 week double-blind study. Aliment Pharmacol Ther 40(1):51–62. CrossRefPubMedGoogle Scholar
  40. 40.
    Williams EA, Stimpson J, Wang D et al (2009) Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther 29(1):97–103. CrossRefPubMedGoogle Scholar
  41. 41.
    Zeng J, Li Y-Q, Zuo X-L et al (2008) Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 28(8):994–1002. CrossRefPubMedGoogle Scholar
  42. 42.
    Sullivan A, Nord CE, Evengård B (2009) Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J 8(1):4. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    van Rosendal SP, Osborne MA, Fassett RG, Coombes JS (2010) Guidelines for glycerol use in hyperhydration and rehydration associated with exercise. Sports Med Auckl NZ 40(2):113–129. CrossRefGoogle Scholar
  44. 44.
    Drossman DA (1999) The Rome criteria process: diagnosis and legitimization of irritable bowel syndrome. Am J Gastroenterol 94(10):2803–2807. CrossRefPubMedGoogle Scholar
  45. 45.
    Thompson WG (1999) The road to Rome. Gut 45:ii80–ii80. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Drossman DA, Hasler WL (2016) Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology 150(6):1257–1261. CrossRefPubMedGoogle Scholar
  47. 47.
    Vork L, Weerts ZZRM, Mujagic Z, Kruimel JW, Hesselink MAM, Muris JWM, Keszthelyi D, Jonkers DMAE, Masclee AAM (2017) Rome III vs Rome IV criteria for irritable bowel syndrome: a comparison of clinical characteristics in a large cohort study. Neurogastroenterol Motil 30(2).
  48. 48.
    Jason LA, Sunnquist M, Brown A, Reed J (2015) Defining essential features of myalgic encephalomyelitis and chronic fatigue syndrome. J Hum Behav Soc Environ 25(6):657–674. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Enck P, Zimmermann K, Menke G, Klosterhalfen S (2009) Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol 47(02):209–214. CrossRefPubMedGoogle Scholar
  50. 50.
    Enck P, Zimmermann K, Menke G et al (2008) 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 20(10):1103–1109. CrossRefPubMedGoogle Scholar
  51. 51.
    Kim HJ, Vazquez Roque MI, Camilleri M et al (2005) A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 17(5):687–696. CrossRefPubMedGoogle Scholar
  52. 52.
    Niedzielin K, Kordecki H, Birkenfeld B (2001) A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol 13(10):1143–1147. CrossRefPubMedGoogle Scholar
  53. 53.
    Compare D, Rocco A, Sgamato C, Coccoli P, Campo SMA, Nazionale I, Larussa T, Luzza F, Chiodini P, Nardone G (2015) Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: a randomized clinical trial. Dig Liver Dis 47(4):273–279. CrossRefPubMedGoogle Scholar
  54. 54.
    Lee J-Y, Chu S-H, Jeon JY, Lee MK, Park JH, Lee DC, Lee JW, Kim NK (2014) Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: a double-blind, randomized, placebo-controlled trial. Dig Liver Dis 46(12):1126–1132. CrossRefPubMedGoogle Scholar
  55. 55.
    Kirchgessner A (2016) The role of the microbiota and potential for dietary intervention in chronic fatigue syndrome. Gut-Brain Axis Elsevier:439–463.

Copyright information

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

Authors and Affiliations

  1. 1.National Centre for Neuroimmunology and Emerging Diseases, Menzies Health InstituteGriffith UniversityGold CoastAustralia
  2. 2.School of Medical ScienceGriffith UniversityGold CoastAustralia

Personalised recommendations