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
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Nagpal R, Neth BJ, Wang S, Craft S, Yadav H
Journal
EBioMedicine
Year
2019
Keywords:
Alzheimer, Dementia, Diet, High fat, Ketogenic, Microbiota, Nutrition, Short-chain fatty acids
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 Aß-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.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Cognitive impairment Abnormality of cognition,Cognitive abnormality,Cognitive defects,Cognitive deficits,Cognitive impairment,Intellectual impairment,cognitive impairment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Cognitive Normal
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mild Cognitive Impairment
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early Mild Cognitive Impairment (diagnosed using ADNI-2 criteria) randomly assigned to either a modified Mediterranean-ketogenic diet (MMKD) or an American heart association diet (AHAD) group
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
- Group 1 sample size Number of subjects in the case (exposed) group
- 11
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Fig. 1d-n and Result text
Description: Differences in the gut microbiome between subjects clinically diagnosed with mild cognitive impairment (MCI) versus cognitively normal (CN) counterparts.
Abundance in Group 1: increased abundance in Mild Cognitive Impairment
| NCBI | Quality Control | Links |
|---|---|---|
| Coprococcus | ||
| Enterobacteriaceae | ||
| Phascolarctobacterium | ||
| Pseudomonadota | ||
| MogibacteriaceaeMogibacteriaceae |
Revision editor(s): MyleeeA, Welile, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Fig. 1d-n and Result text
Description: Differences in the gut microbiome between subjects clinically diagnosed with mild cognitive impairment (MCI) versus cognitively normal (CN) counterparts.
Abundance in Group 1: decreased abundance in Mild Cognitive Impairment
| NCBI | Quality Control | Links |
|---|---|---|
| Dialister |
Revision editor(s): MyleeeA, Scholastica
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Post American heart association diet (AHAD) in MCI
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post modified Mediterranean-ketogenic diet (MMKD) in MCI
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants diagnosed with early mild cognitive impairment (MCI) at endpoint of the modified Mediterranean-ketogenic diet (MMKD) intervention
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Fig. 4 and Text
Description: Significant bacterial taxa at endpoint American heart association diet (Post-AHAD) intervention compared to endpoint modified Mediterranean-ketogenic diet (Post-MMKD) intervention
Abundance in Group 1: decreased abundance in Post modified Mediterranean-ketogenic diet (MMKD) in MCI
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacteriaceae | ||
| Bifidobacterium |
Revision editor(s): MyleeeA, Scholastica
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Post American heart association diet (AHAD) in CN and MCI
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post modified Mediterranean-ketogenic diet (MMKD) in CN and MCI
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- All Participants including cognitively normal (CN) and those diagnosed with early mild cognitive impairment (MCI) at endpoint of the modified Mediterranean-ketogenic diet (MMKD) intervention
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
- Group 1 sample size Number of subjects in the case (exposed) group
- 17
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Fig. 4
Description: Significant bacterial taxa at endpoint American heart association diet (Post-AHAD) intervention compared to endpoint modified Mediterranean-ketogenic diet (Post-MMKD) intervention
Abundance in Group 1: decreased abundance in Post modified Mediterranean-ketogenic diet (MMKD) in CN and MCI
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacteriaceae | ||
| Bifidobacterium |
Revision editor(s): MyleeeA, Scholastica
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre modified Mediterranean-ketogenic diet (MMKD) in CN and MCI
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Suppl. Fig.4.
Description: Lefse analysis showing bacterial taxa contributing to the microbiome difference at baseline (pre) compared to endpoint (post) modified Mediterranean-ketogenic diet (MMKD)
Abundance in Group 1: increased abundance in Post modified Mediterranean-ketogenic diet (MMKD) in CN and MCI
| NCBI | Quality Control | Links |
|---|---|---|
| Lactococcus |
Revision editor(s): MyleeeA, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-5-28
Source: Suppl. Fig.4.
Description: Lefse analysis showing bacterial taxa contributing to the microbiome difference at baseline (pre) compared to endpoint (post) modified Mediterranean-ketogenic diet (MMKD)
Abundance in Group 1: decreased abundance in Post modified Mediterranean-ketogenic diet (MMKD) in CN and MCI
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Bifidobacteriaceae | ||
| Bifidobacteriales | ||
| Bifidobacterium |
Revision editor(s): Scholastica
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