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Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment.
EBioMedicine. 2019 Sep; 47:529-542.E

Abstract

BACKGROUND

Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers.

METHODS

A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ± 6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid β (Aβ)-40 and Aβ-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions.

FINDINGS

At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate.

INTERPRETATION

The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF.

Authors+Show Affiliations

Department of Internal Medicine-Molecular Medicine, Winston-Salem, NC, USA; Department of Microbiology and Immunology, Winston-Salem, NC, USA.Department of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA.Department of Internal Medicine-Molecular Medicine, Winston-Salem, NC, USA; Department of Microbiology and Immunology, Winston-Salem, NC, USA.Department of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: suzcraft@wakehealth.edu.Department of Internal Medicine-Molecular Medicine, Winston-Salem, NC, USA; Department of Microbiology and Immunology, Winston-Salem, NC, USA. Electronic address: hyadav@wakehealth.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31477562

Citation

Nagpal, Ravinder, et al. "Modified Mediterranean-ketogenic Diet Modulates Gut Microbiome and Short-chain Fatty Acids in Association With Alzheimer's Disease Markers in Subjects With Mild Cognitive Impairment." EBioMedicine, vol. 47, 2019, pp. 529-542.
Nagpal R, Neth BJ, Wang S, et al. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019;47:529-542.
Nagpal, R., Neth, B. J., Wang, S., Craft, S., & Yadav, H. (2019). Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment. EBioMedicine, 47, 529-542. https://doi.org/10.1016/j.ebiom.2019.08.032
Nagpal R, et al. Modified Mediterranean-ketogenic Diet Modulates Gut Microbiome and Short-chain Fatty Acids in Association With Alzheimer's Disease Markers in Subjects With Mild Cognitive Impairment. EBioMedicine. 2019;47:529-542. PubMed PMID: 31477562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment. AU - Nagpal,Ravinder, AU - Neth,Bryan J, AU - Wang,Shaohua, AU - Craft,Suzanne, AU - Yadav,Hariom, Y1 - 2019/08/30/ PY - 2019/03/30/received PY - 2019/08/06/revised PY - 2019/08/14/accepted PY - 2019/9/4/pubmed PY - 2020/2/6/medline PY - 2019/9/4/entrez KW - Alzheimer KW - Dementia KW - Diet KW - High fat KW - Ketogenic KW - Microbiota KW - Nutrition KW - Short-chain fatty acids SP - 529 EP - 542 JF - EBioMedicine JO - EBioMedicine VL - 47 N2 - BACKGROUND: Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers. METHODS: A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ± 6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid β (Aβ)-40 and Aβ-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. FINDINGS: At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. INTERPRETATION: The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/31477562/Modified_Mediterranean_ketogenic_diet_modulates_gut_microbiome_and_short_chain_fatty_acids_in_association_with_Alzheimer's_disease_markers_in_subjects_with_mild_cognitive_impairment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(19)30554-7 DB - PRIME DP - Unbound Medicine ER -