The gut microbiome, mild cognitive impairment, and probiotics: A randomized clinical trial in middle-aged and older adults

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-23
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Aljumaah MR, Bhatia U, Roach J, Gunstad J, Azcarate Peril MA
Journal
Clinical nutrition (Edinburgh, Scotland)
Year
2022
Keywords:
Cogitative aging, Gut microbiome, Lactobacillus rhamnosus GG, Prevotella, Psychobiotics
BACKGROUND: Advancing age coincides with changes in the gut microbiome and a decline in cognitive ability. Psychobiotics are microbiota-targeted interventions that can result in mental health benefits and protect the aging brain. This study investigated the gut microbiome composition and predicted microbial functional pathways of middle-aged and older adults that met criteria for mild cognitive impairment (MCI), compared to neurologically healthy individuals, and investigated the impact of probiotic Lactobacillus rhamnosus GG (LGG) in a double-blind, placebo-controlled, randomized clinical trial. A total of 169 community-dwelling middle-aged (52-59 years) and older adults (60-75 years) received a three-month intervention and were randomized to probiotic and placebo groups. Participants were further subdivided based on cognitive status into groups with intact or impaired cognition and samples were collected at baseline and post supplementation. RESULTS: Microbiome analysis identified Prevotella ruminicola, Bacteroides thetaiotaomicron, and Bacteroides xylanisolvens as taxa correlated with MCI. Differential abundance analysis at baseline identified Prevotella as significantly more prevalent in MCI subjects compared to cognitively intact subjects (ALDEx2 P = 0.0017, ANCOM-BC P = 0.0004). A decrease in the relative abundance of the genus Prevotella and Dehalobacterium in response to LGG supplementation in the MCI group was correlated with an improved cognitive score. CONCLUSIONS: Our study points to specific members of the gut microbiota correlated with cognitive performance in middle-aged and older adults. Should findings be replicated, these taxa could be used as key early indicators of MCI and manipulated by probiotics, prebiotics, and symbiotics to promote successful cognitive aging. Registered under ClinicalTrials.gov Identifier no. NCT03080818.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/07/15

Curator: JoyceQ

Revision editor(s): JoyceQ, Victoria

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
Cognitively Intact Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Cognitively Impaired Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of 23 patients with cognitive impairment.
Group 0 sample size Number of subjects in the control (unexposed) group
60
Group 1 sample size Number of subjects in the case (exposed) group
23

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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/08/01

Curator: JoyceQ

Revision editor(s): JoyceQ, Victoria

Source: Figure 2C

Description: Cladogram and linear discriminant analysis of effect size (Lefse) showing biomarker taxa associated with cognitively intact and impaired individuals. The Lefse analysis included non-probiotic groups only.

Abundance in Group 1: increased abundance in Cognitively Impaired Group

NCBI Quality ControlLinks
Phocaeicola coprocola
Phocaeicola massiliensis
Prevotella
Prevotellaceae
Verrucomicrobiota
unclassified Prevotella
uncultured organism
Prevotellaceae NK3B1 groupPrevotellaceae NK3B1 group

Revision editor(s): JoyceQ, Victoria

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/08/02

Curator: JoyceQ

Revision editor(s): JoyceQ, Rahila, Victoria

Source: Figure 2C

Description: Cladogram and linear discriminant analysis of effect size (Lefse) showing biomarker taxa associated with cognitively intact and impaired individuals. The Lefse analysis included non-probiotic groups only.

Abundance in Group 1: decreased abundance in Cognitively Impaired Group

NCBI Quality ControlLinks
Pseudomonadota
Phocaeicola vulgatus

Revision editor(s): JoyceQ, Rahila, Victoria

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Placebo Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients in this group received two Culturelle Placebo Veggie capsules containing microcrystalline cellulose, which the gut microbiota cannot ferment.
Group 0 sample size Number of subjects in the control (unexposed) group
169
Group 1 sample size Number of subjects in the case (exposed) group
83

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: increased abundance in Placebo Group

NCBI Quality ControlLinks
[Ruminococcus] torques group[Ruminococcus] torques group
uncultured organism

Revision editor(s): Victoria

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: decreased abundance in Placebo Group

NCBI Quality ControlLinks
environmental samples

Revision editor(s): Victoria

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Probiotic Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients in this group received an LGG supplement in the form of two Culturelle Vegetarian Capsules containing a 10 billion CFU blend of L. rhamnosus GG and 200mg prebiotic inulin from chicory root extract.
Group 1 sample size Number of subjects in the case (exposed) group
86

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: increased abundance in Probiotic Group

NCBI Quality ControlLinks
uncultured bacterium
Lactobacillus
Lactobacillaceae
Veilonellales selenomonadalesVeilonellales selenomonadales
unidentified
Mogibacterium

Revision editor(s): Victoria

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: decreased abundance in Probiotic Group

NCBI Quality ControlLinks
environmental samples

Revision editor(s): Victoria

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo Group
Group 0 sample size Number of subjects in the control (unexposed) group
83

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: increased abundance in Probiotic Group

NCBI Quality ControlLinks
Lactobacillus
Mogibacterium
uncultured bacterium
unidentified
Veilonellales selenomonadalesVeilonellales selenomonadales
Lactobacillaceae

Revision editor(s): Victoria

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-10-23

Curated date: 2024/10/23

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5D

Description: Cladogram and Linear Discriminant Analysis of effect size (Lefse) showing biomarker taxa for each group.

Abundance in Group 1: decreased abundance in Probiotic Group

NCBI Quality ControlLinks
uncultured organism
[Ruminococcus] torques group[Ruminococcus] torques group

Revision editor(s): Victoria