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

Study information

Needs review

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

36228569

DOI Digital object identifier for electronic documents.

10.1016/j.clnu.2022.09.012

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

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Curated date: 2024/07/15

Curator: JoyceQ

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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

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Curated date: 2024/08/01

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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 Control	Links
Prevotella

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Signature 2

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Source: Results 3.5

Description:

Abundance in Group 1: increased abundance in Probiotic group

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

Revision editor(s): JoyceQ