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

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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


Needs review

Curated date: 2024/07/15

Curator: JoyceQ

Revision editor(s): JoyceQ

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 decline measurement Cognitive decline measurement,cognitive decline measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo group
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
Participants who received L. rhamnosus GG (LGG) supplementation
Group 0 sample size Number of subjects in the control (unexposed) group
83
Group 1 sample size Number of subjects in the case (exposed) group
86
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
90

Lab analysis

Sequencing type
PCR
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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).
centered log-ratio
Statistical test
ANCOM
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

Needs review

Curated date: 2024/08/01

Curator: JoyceQ

Revision editor(s): JoyceQ

Source: Figure 3A and B

Description: "Relative abundance and predicted functional pathways by cognitive status (A) Univariate comparison analysis showing a significant difference in the relative abundance of Prevotella between cognitively intact and impaired groups (KruskaleWallis Adj. p 1⁄4 0.0136). (B) Random Forest analysis between cognitive groups at the genus level (tree n 1⁄4 5000). Genera were ranked by their contributions to classification accuracy (Mean Decrease Accuracy). Extended error bar plot of PICRUSt2 predictions using Welch's test of C ECs and D KOs. All p values were corrected using Benjamin-Hochberg correction."

Abundance in Group 1: increased abundance in Probiotic group

NCBI Quality ControlLinks
Prevotella

Revision editor(s): JoyceQ

Signature 2

Needs review

Curated date: 2024/08/02

Curator: JoyceQ

Revision editor(s): JoyceQ

Source: Results 3.5

Description:

Abundance in Group 1: increased abundance in Probiotic group

NCBI Quality ControlLinks
ProteobacteriaProteobacteria
Gammap- roteobacteriaGammap- roteobacteria
Burkholderiales
Sutterellaceae
Parasutterella
Bacteroidaceae
Bacteroides
PrevotellaceaPrevotellacea
Prevotella
Lachnospiraceae
Clostridium methylpentosum groupClostridium methylpentosum group
Neg- ativbacillusNeg- ativbacillus

Revision editor(s): JoyceQ