The small bowel microbiome changes significantly with age and aspects of the ageing process

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Leite G, Pimentel M, Barlow GM, Mathur R
Journal
Microbial cell (Graz, Austria)
Year
2022
Keywords:
age, aging, coliforms, concomitant diseases, medication use, proteobacteria, small intestinal microbiome
Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer's disease and Parkinson's disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the 'ageing process' (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes. These changes may contribute to changes in human health that occur during the ageing process.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2023/10/18

Curator: Davvve

Revision editor(s): Davvve, ChiomaBlessing

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
Small intestine Anterior intestine,Intestinum tenue,Mid intestine,Small bowel,Small intestine,small intestine
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Aging ageing,AGING BIOL,Aging, Biological,BIOL AGING,Biological Aging,Senescence,Aging,aging
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Group 1- youngest age group (18 to 35 years old)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Group 4- oldest age group (66 to 80 years old. elderly people)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This is the oldest age advanced group from the study
Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
82
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
V3-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
PLS-DA (Partial least square discriminant analysis)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.0001
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2023/10/19

Curator: Davvve

Revision editor(s): Davvve, ChiomaBlessing

Source: Figure S6 + Results (text): Page 6, under sub-heading "Microbiome differences are most pronounced between younger (group 1) and elderly (group 4) adults."

Description: Variable importance in projection (VIP) selected during PLS-DA analysis of families in the duodenal microbiome of subjects in Groups 4 compared to Group 1.

Abundance in Group 1: increased abundance in Group 4- oldest age group (66 to 80 years old. elderly people)

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Clostridiaceae
Desulfovibrionaceae
Enterobacteriaceae
Enterococcaceae
Klebsiella
Lactobacillus
Lactobacillaceae
Escherichia

Revision editor(s): Davvve, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2024/01/30

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure S6

Description: Variable importance in projection (VIP) selected during PLS-DA analysis of families in the duodenal microbiome of subjects in Groups 4 compared to Group 1.

Abundance in Group 1: decreased abundance in Group 4- oldest age group (66 to 80 years old. elderly people)

NCBI Quality ControlLinks
Actinomycetaceae
Carnobacteriaceae
Erysipelotrichaceae
Lachnospiraceae
Leptotrichiaceae
Moraxellaceae
Paraprevotella
Peptostreptococcaceae
Porphyromonadaceae
Prevotellaceae
Pseudomonadaceae
Spirochaetaceae
Tissierellaceae
unclassified Mogibacterium
unclassified Paraprevotella
F16F16

Revision editor(s): ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2024/01/30

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Group 2, 3 and 4 - older age groups (36 to 50 years old; 51 to 65 years old and 66 to 80 years old.)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
These are the remaining 3 groups of subjects grouped according to advancing chronological age (N= 41, 36 to 50 years old; N= 96, 51 to 65 years old and N= 82, 66 to 80 years old).
Group 1 sample size Number of subjects in the case (exposed) group
219

Lab analysis

Statistical Analysis

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)?
No
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "number of medications used" 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.number of medications used, Confounders controlled for: "number of concomitant diseases" 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.number of concomitant diseases

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2024/01/30

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table S2

Description: Facultative and strict anaerobic genera in the duodenal microbiome of older subjects from groups 2, 3, and 4, when compared to group 1

Abundance in Group 1: increased abundance in Group 2, 3 and 4 - older age groups (36 to 50 years old; 51 to 65 years old and 66 to 80 years old.)

NCBI Quality ControlLinks
Actinobacillus
Bacteroides
Escherichia
Lactobacillus

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-30

Curated date: 2024/01/30

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table S2

Description: Facultative and strict anaerobic genera in the duodenal microbiome of older subjects from groups 2, 3, and 4, when compared to group 1

Abundance in Group 1: decreased abundance in Group 2, 3 and 4 - older age groups (36 to 50 years old; 51 to 65 years old and 66 to 80 years old.)

NCBI Quality ControlLinks
Lysobacteraceae

Revision editor(s): ChiomaBlessing