Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study

  • Yodai KobayashiEmail author
  • T. Kinoshita
  • A. Matsumoto
  • K. Yoshino
  • I. Saito
  • J.-Z. Xiao
Short Communication



We previously reported the therapeutic potential of Bifidobacterium breve A1 (B. breve A1) for preventing cognitive impairment in Alzheimer’s disease model mice, which suggested that supplementation of the probiotics could be an effective therapeutic strategy for managing cognitive function in mild cognitive impairment (MCI).

Design and Settings

We conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on elderly with MCI in Aki Orthopedics Rehabilitation Clinic in Japan.


27 participants were screened by their Mini Mental State Examination (MMSE) scores.


Cognitive function was assessed using MMSE and Digit Symbol Substitution Test (DSST) at baseline and every 8 weeks. Mental condition and quality of life for gastrointestinal symptoms were measured using the Profile of Mood States 2nd Edition (POMS2), and the Gastrointestinal Symptom Rating Scale (GSRS).


Of the 27 participants enrolled, 19 completed the study. MMSE scores were significantly increased during the intervention by mixed model Dunnett’s test and Wilcoxon signed-rank tests (+1.7, P < 0.01). POMS2 and GSRS scores were significantly improved during intervention when analyzed by Wilcoxon signed-rank tests.


The present study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function, thus suggesting the potential of B. breve A1 for improving cognitive function and maintaining quality of life of the elderly. Further randomized, double-blind placebo-controlled studies are worth conducting to examine the beneficial effect of B. breve A1.

Key words

Dementia Alzheimer’s disease Bifidobacterium cognitive impairment probiotics 


  1. 1.
    Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–2117.CrossRefGoogle Scholar
  2. 2.
    Langa KM, Chernew ME, Kabeto MU, Herzog AR, Ofstedal MB, Willis RJ et al. National estimates of the quantity and cost of informal caregiving for the elderly with dementia. J Gen Intern Med 2001; 16: 770–8.CrossRefGoogle Scholar
  3. 3.
    Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 2010; 9: 119–128.CrossRefGoogle Scholar
  4. 4.
    Petersen RC. Clinical practice. Mild cognitive impairment. N Engl J Med 2011; 364: 2227–34.Google Scholar
  5. 5.
    Ataollahi Eshkoor S, Mun CY, Ng CK, Hamid TA. Mild cognitive impairment and its management in&nbsp;older people. Clin Interv Aging 2015; 10: 687.CrossRefGoogle Scholar
  6. 6.
    Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol 2010; 7: 503–514.CrossRefGoogle Scholar
  7. 7.
    Sampson TR, Mazmanian SK. Control of Brain Development, Function, and Behavior by the Microbiome. Cell Host Microbe 2015; 17: 565–576.CrossRefGoogle Scholar
  8. 8.
    Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil 2014; 26: 510–20.CrossRefGoogle Scholar
  9. 9.
    Akbari E, Asemi Z, Daneshvar Kakhaki R, Bahmani F, Kouchaki E, Tamtaji OR et al. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci 2016; 8: 256.CrossRefGoogle Scholar
  10. 10.
    Alkasir R, Li J, Li X, Jin M, Zhu B. Human gut microbiota: the links with dementia development. Protein Cell 2017; 8: 90–102.CrossRefGoogle Scholar
  11. 11.
    Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep 2017; 7: 13510.CrossRefGoogle Scholar
  12. 12.
    Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms Underlying Inflammation in Neurodegeneration. Cell 2010; 140: 918–934.CrossRefGoogle Scholar
  13. 13.
    Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98.Google Scholar
  14. 14.
    D’Cunha NM, Georgousopoulou EN, Dadigamuwage L, et al. Effect of longterm nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. Br J Nutr. 2018;119(3):280–298.CrossRefGoogle Scholar
  15. 15.
    Izawa Y, Urakami K, Kojima T, Ohama E. Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III): Usefulness in the Early Detection of Alzheimer’s Disease. Yonago Acta Med 2009; 52: 11–20.Google Scholar
  16. 16.
    Kazuhito Y, Kazuhisa W. Profile of Mood States 2nd Edition Japanese Manual (in Japanese). Kaneko shobo, Japan.Google Scholar
  17. 17.
    Svedlund J, Sjödin I, Dotevall G. GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 1988; 33: 129–34.CrossRefGoogle Scholar
  18. 18.
    Laurence BD, Michel L. The Fall in Older Adults: Physical and Cognitive Problems. Curr Aging Sci 2017; 10: 185–200.CrossRefGoogle Scholar
  19. 19.
    Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002; 288: 1475–83.CrossRefGoogle Scholar
  20. 20.
    Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H et al. Neuroinflammation Induces Neurodegeneration. J Neurol Neurosurg spine 2016; 1.Google Scholar
  21. 21.
    Portincasa P, Maggipinto A, Berardino M, Bonfrate L, Costin S, Todarello O et al. Assessing gastrointestinal symptoms and perception, quality of life, motility, and autonomic neuropathy in clinical studies. J Gastrointestin Liver Dis 2009; 18: 205–11.Google Scholar
  22. 22.
    Kondo J, Xiao J-Z, Shirahata A, Baba M, Abe A, Ogawa K et al. Modulatory effects of Bifidobacterium longum BB536 on defecation in elderly patients receiving enteral feeding. World J Gastroenterol 2013; 19: 2162–70.CrossRefGoogle Scholar
  23. 23.
    Blum S, Schiffrin EJ. Intestinal microflora and homeostasis of the mucosal immune response: implications for probiotic bacteria? Curr Issues Intest Microbiol 2003; 4: 53–60.Google Scholar

Copyright information

© Serdi Edition 2018

Authors and Affiliations

  • Yodai Kobayashi
    • 1
    Email author
  • T. Kinoshita
    • 2
    • 3
  • A. Matsumoto
    • 4
  • K. Yoshino
    • 4
  • I. Saito
    • 2
  • J.-Z. Xiao
    • 1
  1. 1.Morinaga Milk Industry Co., Ltd., Next Generation Science InstituteKanagawaJapan
  2. 2.Department of Community Health Systems NursingEhime University Graduate School of MedicineToon, EhimeJapan
  3. 3.Institute of Community Life Sciences Co., LtdMatsuyama, EhimeJapan
  4. 4.Aki Orthopedics Rehabilitation ClinicMatsuyama, EhimeJapan

Personalised recommendations