Research Paper Volume 12, Issue 23 pp 24371—24393

Mental awareness improved mild cognitive impairment and modulated gut microbiome

Wei Wei Thwe Khine1,2, , Miao Lian Voong1, , Ted Kheng Siang Ng3, , Lei Feng3,4, , Grishma Avinash Rane5, , Alan Prem Kumar5,6,7, , Ee Heok Kua3,4, , Ratha Mahendran8, , Rathi Mahendran3,4,9, *, , Yuan-Kun Lee1,8, *, ,

  • 1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
  • 2 Functional Foods Forum, Faculty of Medicine, University of Turku, Turku 20014, Finland
  • 3 Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117549, Singapore
  • 4 Department of Psychological Medicine, National University Hospital, Singapore 119228, Singapore
  • 5 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
  • 6 Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
  • 7 Medical Sciences Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
  • 8 Department of Surgery, National University Hospital, Singapore 119228, Singapore
  • 9 Duke-NUS Medical School, Singapore 169857, Singapore
* Equal contribution

Received: April 30, 2020       Accepted: November 13, 2020       Published: December 9, 2020
How to Cite

Copyright: © 2020 Khine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


There is ample scientific and clinical evidence of the effects of gut microbiota on the brain but no definitive evidence that the brain can affect changes in gut microbiota under the bi-directional gut-brain axis concept. As there is no pharmacotherapeutic intervention for the early stages of cognitive decline, research has focused on cognitive stimulation in reversing or slowing the impairment. Elderly patients diagnosed with mild cognitive impairment underwent a randomized-control trial of mindful awareness practice. Neuropsychological assessments, inflammatory markers, and gut microbiota profiles were tested. Here, we report that their cognitive impairment was improved and associated with changes in gut bacterial profile. A cognition-score-dependent-abundance was observed in Ruminococcus vs Recognition Trials (RT), Digit Span Backward (DSB), Semantic Fluency Span (SFS) and Memory Domain (MD); Coprococcus vs DSB, Color Trails Test 2 (CTT2) and Block Design (BD); Parabacteroides vs DSB and SFS; Fusobacterium vs DSB and CTT2; Enterobacteriaceae vs BD and SFS; Ruminococcaceae vs DSB; Phascolarctobacterium vs MD. The study showed for the first-time, alteration in the cognitive capacity leading to the corresponding changes in microbiota profiles. This strongly suggests that signals from the different segments of brain could dictate directly or indirectly the abundances of specific gut microbes.


RT: Recognition Trials; DSB: Digit Span Backward; SFS: Semantic Fluency Span; MD: Memory Domain; CTT2: Color Trails Test 2; BD: Block Design; MCI: Mild Cognitive Impairment; DSM: Diagnostic and statistical manual of mental disorders; GI: Gastrointestinal tract; MAP: Mindful Awareness Program; db-RDA: Distance-based redundancy analysis; PCoA: Principal coordinates analysis; BDNF: Brain-derived neurotrophic factor; TL: Telomere length; DHEAS: Dehydroepiandrosterone sulfate; CRP: C-reactive protein; IL: Interleukin; IL-1β: Interleukin-1 beta; TNFα: Tumor necrosis factor alpha; IFNγ: Interferon gamma; GM-CSG: Granulocyte-macrophage colony-stimulating factor; fMRI: functional Magnetic Resonance Imaging; TaRA: Training and Research Academy; DSM: Diagnostic and Statistical Manual of Mental Disorders; FFQ: Food Frequency Questionnaire; MMSE: Mini-Mental State Examination; CDR: Clinical Dementia Rating; RAVLT: Rey Auditory Verbal Learning Test; GDS: Geriatric Depression Scale; GAI: Geriatric Anxiety Index; EDTA: Ethylenediaminetetraacetic acid; TRF: Telomere restriction fragment; ELISA: Enzyme-linked Immunosorbent Assay; PBS: Phosphate buffered saline; TE: Tris-EDTA; DNA: Double-stranded Nucleic Acid; rRNA: ribosomal ribonucleic acid; PCR: Polymerase Chain Reaction; PAL: Pooled Amplicon Library; QIIME: Quantitative insights into microbial ecology; OTU: Operational taxonomical unit; PMSF: Phenylmethylsulfonyl fluoride; BSA: Bovine serum albumin; PERMANOVA: Permutational multivariate analysis of variance.