Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Ni Lochlainn M, Bowyer RCE, Moll JM, García MP, Wadge S, Baleanu AF, Nessa A, Sheedy A, Akdag G, Hart D, Raffaele G, Seed PT, Murphy C, Harridge SDR, Welch AA, Greig C, Whelan K, Steves CJ
Journal
Nature communications
Year
2024
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Experiment 1


Needs review

Curated date: 2024/10/07

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, MyleeeA

Subjects

Location of subjects
United Kingdom
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
Diet Dietary,Diets,Diet,diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo group (End of study)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prebiotic group (End of study)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Subjects who received prebiotic supplements (inulin and fructo-oligosaccharides) along with BCAA (branched-chain amino acid) supplementation and resistance exercise and follow up was done after 12 weeks.
Group 0 sample size Number of subjects in the control (unexposed) group
34
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months.

Lab analysis

Sequencing type
WMS
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
Linear Regression
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
Matched on Factors on which subjects have been matched on in a case-control study
Matched on: "twin pairs" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.twin pairs
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, diet, sex, Confounders controlled for: "appetite score" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.appetite score, Confounders controlled for: "zygosity" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.zygosity


Signature 1

Needs review

Curated date: 2024/10/07

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, Rahila, Chrisawoke

Source: Figure 2

Description: Twin-paired group comparisons between prebiotic and placebo supplements, including data from the end of the study or the difference between baseline and end of study.

Abundance in Group 1: increased abundance in Prebiotic group (End of study)

NCBI Quality ControlLinks
Actinomycetes
Actinomycetota
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium

Revision editor(s): Rukaya-lab, Rahila, Chrisawoke

Signature 2

Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Source: Figure 2

Description: Twin-paired group comparisons between prebiotic and placebo supplements, including data from the end of the study or the difference between baseline and end of study.

Abundance in Group 1: decreased abundance in Prebiotic group (End of study)

NCBI Quality ControlLinks
Bacillota
Bacteroidales
Clostridia
Eubacteriales
Merdimmobilis
Merdimmobilis hominis

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Experiment 2


Needs review

Curated date: 2024/10/08

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo (change between baseline and study end)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prebiotic(change between baseline and study end)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Subjects who received prebiotic supplements (inulin and fructo-oligosaccharides) along with BCAA (branched-chain amino acid) supplementation and resistance exercise and follow up was done after 12 weeks. Study end was adjusted for baseline in this experiment.
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "time point" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.time point, Confounders controlled for: "twin pair" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.twin pair


Signature 1

Needs review

Curated date: 2024/10/08

Curator: Rukaya-lab

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Source: Figure 2

Description: Twin-paired group comparisons between prebiotic and placebo supplements, including data from the end of the study or the difference between baseline and end of study.

Abundance in Group 1: increased abundance in Prebiotic(change between baseline and study end)

NCBI Quality ControlLinks
Bifidobacterium
Bifidobacteriaceae
Bifidobacteriales
Actinomycetes

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Signature 2

Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Source: Figure 2

Description: Twin-paired group comparisons between prebiotic and placebo supplements, including data from the end of the study or the difference between baseline and end of study.

Abundance in Group 1: decreased abundance in Prebiotic(change between baseline and study end)

NCBI Quality ControlLinks
Acidaminococcales
Anaeromassilibacillus
Bacillota
Bacteroidales
Bacteroidota
Clostridia
Deltaproteobacteria
Desulfovibrionales
Eubacteriales
Eubacterium sp. AF17-7
Lactobacillales
Merdimmobilis
Merdimmobilis hominis

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Experiment 3


Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Placebo
Group 1 name Corresponds to the case (exposed) group for case-control studies
End of Study Placebo
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Week 12 (End of study) participants who received protein (BCAA) supplement powder combined with a placebo supplement (maltodextrin).
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
34

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "baseline microbiota" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.baseline microbiota, Confounders controlled for: "zygosity" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.zygosity

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, Rahila, Chrisawoke

Source: Figure S6

Description: Significant Microbiota Features between Baseline and Study End

Abundance in Group 1: increased abundance in End of Study Placebo

NCBI Quality ControlLinks
Actinomyces graevenitzii

Revision editor(s): Rukaya-lab, Rahila, Chrisawoke

Experiment 4


Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): Rukaya-lab, MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Prebiotic
Group 1 name Corresponds to the case (exposed) group for case-control studies
End of study Prebiotic
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Week 12 (End of study) participants who received daily prebiotic supplementation (inulin and fructo-oligosaccharides) along with branched-chain amino acids (BCAA) and resistance exercise.
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months.

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "zygosity" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.zygosity, Confounders controlled for: "baseline microbiota" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.baseline microbiota

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Source: Supplementary Figure S6

Description: Significant Microbiota Features identified between Baseline Prebiotic and Study End Prebiotic using Linear models.

Abundance in Group 1: increased abundance in End of study Prebiotic

NCBI Quality ControlLinks
Actinomyces graevenitzii
Actinomycetaceae
Actinomycetales
Actinomycetes
Actinomycetota
Anaerostipes hadrus
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Bifidobacterium dentium
Bifidobacterium longum
Candidatus Nanosynbacter
Candidatus Nanosynbacteraceae
Candidatus Nanosynbacterales
Candidatus Saccharibacteria
Candidatus Saccharimonadia
Parvimonas
Schaalia
Schaalia odontolytica
Streptococcus oralis
Anaerostipes
Intestinimonas sp. MSJ-38

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Signature 2

Needs review

Curated date: 2024/10/11

Curator: Rukaya-lab

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Source: Supplementary Figure S6

Description: Significant Microbiota Features identified between Baseline Prebiotic and Study End Prebiotic using Linear models.

Abundance in Group 1: decreased abundance in End of study Prebiotic

NCBI Quality ControlLinks
Anaeromassilibacillus
Bigyra
Clostridia
Deltaproteobacteria
Eubacterium
Merdimmobilis
Merdimmobilis hominis
Methanobacteria
Negativicutes
Ruminococcus
Waltera
[Ruminococcus] torques
Lachnospiraceae bacterium NSJ 29Lachnospiraceae bacterium NSJ 29
Clostridium sp. AF34-10BH
Methanobacteriota
Eubacterium sp. AF17-7

Revision editor(s): MyleeeA, Rahila, Chrisawoke, Rukaya-lab

Experiment 5


Needs review

Curated date: 2024/10/24

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline prebiotics and placebo
Group 1 name Corresponds to the case (exposed) group for case-control studies
End of study prebiotics and placebo
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Week 12 (End of study) participants who received protein (BCAA) supplement powder combined with a placebo supplement (maltodextrin) and daily prebiotic supplementation (inulin and fructo-oligosaccharides) along with branched-chain amino acids (BCAA) and resistance exercise.
Group 0 sample size Number of subjects in the control (unexposed) group
70
Group 1 sample size Number of subjects in the case (exposed) group
68
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 Months

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/27

Curator: Chrisawoke

Revision editor(s): Chrisawoke

Source: Figure S6

Description: Significant Microbiota Features Between Baseline and Study End

Abundance in Group 1: increased abundance in End of study prebiotics and placebo

NCBI Quality ControlLinks
Anaerostipes
Actinomyces graevenitzii
Anaerostipes hadrus
Parvimonas micra

Revision editor(s): Chrisawoke

Experiment 6


Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo (Correlated with Cognition Factor)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prebiotic (Correlated with Cognition Factor)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Week 12 (End of study) participants in prebiotic group positively correlated with Cognition Factor.
Group 0 sample size Number of subjects in the control (unexposed) group
34
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 Months.

Lab analysis

Statistical Analysis

Statistical test
Pearson Correlation


Signature 1

Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 9 and 10

Description: Microbiota features that positively correlated with Cognition Factor.

Abundance in Group 1: increased abundance in Prebiotic (Correlated with Cognition Factor)

NCBI Quality ControlLinks
Veillonellaceae
Veillonellales
Coriobacteriales
Actinomycetota

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 9 and 10

Description: Microbiota features that Negatively correlated with Cognition Factor.

Abundance in Group 1: decreased abundance in Prebiotic (Correlated with Cognition Factor)

NCBI Quality ControlLinks
Lacrimispora

Revision editor(s): MyleeeA

Experiment 7


Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Placebo (Correlated with Chair Rise time)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prebiotic (Correlated with Chair Rise time)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Week 12 (End of study) participants in prebiotic group positively correlated with Chair Rise time (CST).
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 Months

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA, Chrisawoke

Source: Supplementary Figure 8

Description: Microbiota features that Positively correlated with Physical Activity (Chair Rise Time).

Abundance in Group 1: increased abundance in Prebiotic (Correlated with Chair Rise time)

NCBI Quality ControlLinks
Acidaminococcus
Acidaminococcus intestini
Anaeromassilibacillus sp. An250
Bacillales
Bittarella massiliensis (ex Durand et al. 2017)
Blautia producta
Citrobacter freundii
Clostridiales bacterium CCNA10
Clostridium sp. AT4
Coprobacillus
Coprobacillus cateniformis
Dysosmobacter welbionis
Enterocloster
Enterocloster aldenensis
Eubacteriales Family XIII. Incertae Sedis
Faecalicatena
Faecalitalea
Faecalitalea cylindroides
Flavonifractor
Flavonifractor plautii
Hoylesella timonensis
Hungatella hathewayi
Hydrogeniiclostridium
Hydrogeniiclostridium mannosilyticum
Klebsiella oxytoca
Lactiplantibacillus
Lactiplantibacillus paraplantarum
Lactobacillus gasseri
Limosilactobacillus
Limosilactobacillus fermentum
Mediterraneibacter gnavus
Merdimonas faecis
Porphyromonas somerae
Prevotella corporis
Rubneribacter badeniensis
Ruthenibacterium
Ruthenibacterium lactatiformans
Schaalia turicensis
Sellimonas
Sellimonas intestinalis
Solobacterium
Solobacterium moorei
Streptococcus mutans
Streptococcus thermophilus
Thomasclavelia ramosa
Thomasclavelia spiroformis
[Clostridium] innocuum
[Clostridium] scindens
[Clostridium] symbiosum
[Collinsella] massiliensis
[Ruminococcus] torques
Agathobaculum faecis
Wansuia hejianensis

Revision editor(s): MyleeeA, Chrisawoke

Signature 2

Needs review

Curated date: 2024/10/25

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 8

Description: Microbiota features that Negatively correlated with Physical Activity (Chair Rise Time).

Abundance in Group 1: decreased abundance in Prebiotic (Correlated with Chair Rise time)

NCBI Quality ControlLinks
Acetivibrio
Agathobaculum butyriciproducens
Akkermansia
Anaerotignum
Anaerotignum faecicola
Blautia glucerasea
Butyricimonas
Christensenellales
Coprococcus
Coprococcus eutactus
Dorea formicigenerans
Dorea sp. AF36-15AT
Eubacterium ramulus
Eubacterium sp. AF17-7
Faecalibacterium
Faecalimonas
Faecalimonas umbilicata
Gemmiger
Gemmiger formicilis
Lachnospira
Oscillibacter
Parabacteroides merdae
Phocaeicola
Subdoligranulum
Verrucomicrobiales
Victivallales
Victivallis
Blautia sp. AF34-10
Clostridium sp. AF37-5
Faecalibacterium longum
Thomasclavelia saccharogumia
Faecalibacterium sp. CLA -AA-H233Faecalibacterium sp. CLA -AA-H233
Intestinimonas sp. MSJ-38
Roseburia sp. OM04-15AA
Clostridium sp. TM06-18
Blautia sp. SG-772
Clostridium sp. OF03-18AA
Subdoligranulum sp. APC924/74
Candidatus Borkfalkia
Massilicoli
Faecalibacillus
Waltera

Revision editor(s): MyleeeA