Therapeutics

Bifidobacterium breve A1

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Overview

Name: Bifidobacterium breve A1
Synonyms: MCC1274, B. breve
Therapy Type: Supplement, Dietary (timeline)
Target Type: Other (timeline)
Condition(s): Mild Cognitive Impairment
U.S. FDA Status: Mild Cognitive Impairment (Phase 2)
Company: Morinaga Milk Industry Co., Ltd

Background

Bifidobacterium breve A1 is a proprietary strain of probiotic bacteria isolated from the intestinal tract of an infant. A main component of the human gut microbiome, Bifidobacteria species form part of  many probiotic supplements widely used to treat gastrointestinal and other ailments (see WebMD). Bifidobacteria are associated with anti-inflammatory and immune-modulatory effects that are generally thought to promote health, but are not understood in detail.

Some studies have reported that intestinal flora influence microglia activity, brain amyloid deposition, and cognition in mouse models of Alzheimer’s disease and in people, implying a potential for probiotic use in preventing dementia (Apr 2020 conference news; Cattaneo et al., 2017).

In preclinical work, feeding mice Bifidobacterium breve A1 prevented cognitive deficits after brain injection of Aβ peptide. Probiotic treatment suppressed Aβ-mediated induction of inflammatory and immune genes in the hippocampus.  (Kobayashi et al., 2017).

Several different probiotic mixtures containing Bifidobacterium yielded broadly similar results in rodent models (Mehrabadi and Sadr, 2020; Wang et al., 2020; Yang et al., 2020; Rezaeiasl et al. 2019).

The mechanisms by which probiotic supplementation affects the brain remains to be clarified. In Kobayashi et al., 2017, the effects of B. breve were partially mimicked by giving mice non-viable bacteria, or the bacterial metabolic product acetate.

Findings

A double-blind trial, conducted in 38 cognitively normal Japanese people in their 60s and 70s, evaluated whether a 12-week regimen of probiotic Bifidobacteria supplementation combined with resistance training exercise improved cognitive functions and other health outcomes. The combined intervention was reported to have led to improvement on the Japanese version of the MoCA screen, as well as lower depression/anxiety scores and body mass index, over placebo (Inoue et al., 2018). 

In an open-label pilot study in Japan, 27 elderly people with mild cognitive impairment took capsules of B. breve A1 daily for 24 weeks. Nineteen completed the study. Their Mini-Mental State Exam (MMSE) scores improved, as did measures of mood and gastrointestinal function (Kobayashi et al., 2019).

A subsequent double-blind trial enrolled 121 elderly Japanese with self-reported memory complaints and MMSE scores between 22 and 27. They ingested two capsules per day of freeze-dried B. breve, containing a total of 2 x 1010 viable bacteria, or placebo, for 12 weeks. Dual endpoints were change in the Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and MMSE. The treatment had no effect overall, as the placebo and B. breve groups improved equally on both measures. When the investigators analyzed subgroups with high RBANS (above 41, in the cognitively normal range), or low RBANS (below 41, in the MCI range) scores at baseline,  the latter showed improvement on the MMSE compared with placebo (Kobayashi et al., 2019).

A second placebo-controlled study in Japan enrolled 80 people age 50 to 79 with suspected mild cognitive impairment and RBANS scores between 11 and 45. Participants received the same daily B. breve or placebo regimen as the previous trial, for 16 weeks. The primary endpoint was change in Japanese RBANS; the Japanese version of the MCI screen (JMCIS) was a secondary measure. All but one person completed the study, with no adverse events reported. Treatment resulted in a 17.6-point improvement in RBANS, compared with a 5.9-point improvement in the placebo group. Treatment was associated with score increases over placebo in immediate memory, visuospatial/constructional, and delayed memory subscales. The JMCIS showed a trend toward more improvement in treated versus placebo (Xiao et al., 2020).

No completed or ongoing B. brevis A1 trials are found in registries. Other Bifidobacterium strains are being evaluated in registered trials for obesity and other metabolic disorders, gastrointestinal conditions, and autism. For more details, see clinicaltrials.gov.

Last Updated: 16 Jul 2020

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References

News Citations

  1. ‘Working from Home’: Do Gut Microbes Hold Sway Over Glia, Aβ?

Paper Citations

  1. Inoue T, Kobayashi Y, Mori N, Sakagawa M, Xiao JZ, Moritani T, Sakane N, Nagai N. Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects. Benef Microbes. 2018 Dec 7;9(6):843-853. Epub 2018 Sep 10 PubMed.
  2. Kobayashi Y, Kinoshita T, Matsumoto A, Yoshino K, Saito I, Xiao JZ. Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study. J Prev Alzheimers Dis. 2019;6(1):70-75. PubMed.
  3. Kobayashi Y, Kuhara T, Oki M, Xiao JZ. Effects of Bifidobacterium breve A1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial. Benef Microbes. 2019 May 28;10(5):511-520. Epub 2019 May 15 PubMed.
  4. Xiao J, Katsumata N, Bernier F, Ohno K, Yamauchi Y, Odamaki T, Yoshikawa K, Ito K, Kaneko T. Probiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2020;77(1):139-147. PubMed.
  5. Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C, Bianchetti A, Volta GD, Turla M, Cotelli MS, Gennuso M, Prelle A, Zanetti O, Lussignoli G, Mirabile D, Bellandi D, Gentile S, Belotti G, Villani D, Harach T, Bolmont T, Padovani A, Boccardi M, Frisoni GB, INDIA-FBP Group. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017 Jan;49:60-68. Epub 2016 Aug 31 PubMed.
  6. Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A, Kondo T, Abe K, Xiao JZ. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease. Sci Rep. 2017 Oct 18;7(1):13510. PubMed.
  7. Mehrabadi S, Sadr SS. Assessment of Probiotics Mixture on Memory Function, Inflammation Markers, and Oxidative Stress in an Alzheimer's Disease Model of Rats. Iran Biomed J. 2020 Jul;24(4):220-8. Epub 2020 Feb 29 PubMed.
  8. Wang F, Xu T, Zhang Y, Zheng T, He Y, He F, Jiang Y. Long-term combined administration of Bifidobacterium bifidum TMC3115 and Lactobacillus plantarum 45 alleviates spatial memory impairment and gut dysbiosis in APP/PS1 mice. FEMS Microbiol Lett. 2020 Apr 1;367(7) PubMed.
  9. Yang X, Yu D, Xue L, Li H, Du J. Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Acta Pharm Sin B. 2020 Mar;10(3):475-487. Epub 2019 Jul 7 PubMed.
  10. Rezaeiasl Z, Salami M, Sepehri G. The Effects of Probiotic Lactobacillus and Bifidobacterium Strains on Memory and Learning Behavior, Long-Term Potentiation (LTP), and Some Biochemical Parameters in β-Amyloid-Induced Rat's Model of Alzheimer's Disease. Prev Nutr Food Sci. 2019 Sep;24(3):265-273. Epub 2019 Sep 30 PubMed.

External Citations

  1. clinicaltrials.gov
  2. WebMD

Further Reading

Papers

  1. Krüger JF, Hillesheim E, Pereira AC, Camargo CQ, Rabito EI. Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2020 Jun 18; PubMed.
  2. Xu M, Mo X, Huang H, Chen X, Liu H, Peng Z, Chen L, Rong S, Yang W, Xu S, Liu L. Yeast β-glucan alleviates cognitive deficit by regulating gut microbiota and metabolites in Aβ1-42-induced AD-like mice. Int J Biol Macromol. 2020 Oct 15;161:258-270. Epub 2020 Jun 6 PubMed.
  3. Wang H, Lee IS, Braun C, Enck P. Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review. J Neurogastroenterol Motil. 2016 Oct 30;22(4):589-605. PubMed.