Effects of proton pump inhibitor on the human gut microbiome profile in multi-ethnic groups in Singapore

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Koo SH, Deng J, Ang DSW, Hsiang JC, Lee LS, Aazmi S, Mohamed EHM, Yang H, Yap SY, Teh LK, Salleh MZ, Lee EJD, Ang TL
Journal
Singapore medical journal
Year
2019
Keywords:
gastroesophageal reflux disease, gastrointestinal microbiome, omeprazole
INTRODUCTION: The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. CONCLUSION: The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-17

Curated date: 2024/03/06

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Subjects

Location of subjects
Singapore
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
Health study participation health questionnaire participation,health survey participation,Health study participation,health study participation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Day 1 participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
Day 7 participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The day participants stopped the course of Omeprazole at therapeutic dose (20mg daily)
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
34
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

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
Kruskall-Wallis
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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2.0

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
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-17

Curated date: 2024/03/06

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5a (3rd Cladogram)

Description: Significant taxa abundance in participants at Day 7 after a course of Omeprazole (20 mg) compared to Day 1

Abundance in Group 1: increased abundance in Day 7 participants

NCBI Quality ControlLinks
Bacilli
Johnsonella
Lactobacillales
Streptococcaceae
Streptococcus
Streptococcus parasanguinis
Veillonella
Veillonella atypica
Veillonella dispar
Veillonella montpellierensis
Veillonella parvula
Streptococcus vestibularis
Ligilactobacillus salivarius
Lelliottia amnigena
Enterobacter ludwigii
Enterobacter
Haemophilus parainfluenzae
Pasteurellaceae
Pasteurellales
Veillonella denticariosi
Johnsonella ignava
Prevotella bivia

Revision editor(s): Deacme, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-17

Curated date: 2024/03/06

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5a (3rd Cladogram)

Description: Significant taxa abundance in participants at Day 7 after a course of Omeprazole (20 mg) compared to Day 1

Abundance in Group 1: decreased abundance in Day 7 participants

NCBI Quality ControlLinks
Collinsella tanakaei
Thermoanaerobacterales
Enterobacteriaceae
Enterobacterales
Gammaproteobacteria

Revision editor(s): Deacme, ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-17

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Day 7
Group 1 name Corresponds to the case (exposed) group for case-control studies
Day 14
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The day that marked the 7th day after participants stopped the course of Omeprazole at therapeutic dose (20mg daily)

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 ChiomaBlessing on 2024-3-17

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5a (2nd Cladogram)

Description: Significant taxa abundance in participants at Day 14 after they stopped the course of Omeprazole (20 mg) compared to Day 7

Abundance in Group 1: increased abundance in Day 14

NCBI Quality ControlLinks
Anaerostipes
Anaerotruncus
Anaerotruncus colihominis
Bacteroidales
Bacteroidia
Turicibacter
Turicibacteraceae
TuricibacteralesTuricibacterales

Revision editor(s): Deacme, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-17

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5a (2nd cladogram)

Description: Significant taxa abundance in participants at Day 14 after they stopped the course of Omeprazole (20 mg) compared to Day 7

Abundance in Group 1: decreased abundance in Day 14

NCBI Quality ControlLinks
Bacilli
Enterobacter
Enterobacterales
Enterobacteriaceae
Erwinia
Erwinia billingiae
Gammaproteobacteria
Haemophilus parainfluenzae
Lactobacillales
Lelliottia amnigena
Mannheimia
Pasteurellaceae
Pasteurellales
Streptococcaceae
Streptococcus
Streptococcus parasanguinis
Veillonella
Veillonella atypica
Veillonella denticariosi
Veillonella montpellierensis
Caldilineaceae
Caldilinea
Caldilineales
Anaerolineae
Caldilinea tarbellica
Ligilactobacillus salivarius
Johnsonella ignava
Johnsonella
Veillonella dispar
Veillonella parvula
Enterobacter soli
Haemophilus
Mannheimia caviae

Revision editor(s): Deacme, ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Chinese participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
Indian participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants who belong to the Indian ethnic group
Group 0 sample size Number of subjects in the control (unexposed) group
12
Group 1 sample size Number of subjects in the case (exposed) group
10

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 ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5b (1st cladogram)

Description: Significant taxa abundance in participants of Indian descent compared to participants of Chinese descent

Abundance in Group 1: increased abundance in Indian participants

NCBI Quality ControlLinks
Erysipelothrix

Revision editor(s): Deacme, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5b (1st cladogram)

Description: Significant taxa abundance in participants of Indian descent compared to participants of Chinese descent

Abundance in Group 1: decreased abundance in Indian participants

NCBI Quality ControlLinks
Anaerotruncus colihominis
Verrucomicrobiaceae
Akkermansia muciniphila
Verrucomicrobiales
Fusobacterium naviforme

Revision editor(s): Deacme, ChiomaBlessing

Experiment 6


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Indian participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
Malay participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants who belong to the Malay ethnic group
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
12

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 ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5b (1st cladogram)

Description: Significant taxa abundance in participants of Malay descent compared to participants of Indian descent

Abundance in Group 1: increased abundance in Malay participants

NCBI Quality ControlLinks
Sutterella stercoricanis
Klebsiella granulomatis

Revision editor(s): Deacme, ChiomaBlessing

Experiment 7


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Male participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
Female participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants who identify with the female gender
Group 0 sample size Number of subjects in the control (unexposed) group
16
Group 1 sample size Number of subjects in the case (exposed) group
18

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 ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5c

Description: Significant taxa abundance in Female participants compared to Male participants

Abundance in Group 1: increased abundance in Female participants

NCBI Quality ControlLinks
Acidaminococcus intestini
Bacteroides clarus
Bacteroides thetaiotaomicron
Bacteroides xylanisolvens
Hoylesella buccalis
Sphingobacteriaceae
Sphingobacteriales
Sphingobacteriia
Sphingobacterium
Sphingobacterium shayense

Revision editor(s): Deacme, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-18

Curated date: 2024/03/07

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Source: Fig 5c

Description: Significant taxa abundance in Female participants compared to Male participants

Abundance in Group 1: decreased abundance in Female participants

NCBI Quality ControlLinks
Anaerolineae
Caldilinea
Caldilinea tarbellica
Caldilineaceae
Caldilineales
Lactobacillaceae
Lactobacillus
Oribacterium
Oribacterium sinus
Fusobacterium naviforme

Revision editor(s): Deacme, ChiomaBlessing

The taxa of Proteobacteria phylum, Gammaproteobacteria class, Enterobacteriales order and Enterobacteriaceae family were only associated with the Day 7 group when it was compared to the Day 14 group, but not when the Day 7 group was compared to that from Day 1 (data not shown).

There was a significant increase in the relative abundance of the Bacilli class, Lactobacillales order, Streptococcaceae family, Streptococcus and Veillonella genera and Streptococcus vestibularis and Veillonella dispar species immediately after PPI use (Day 7), which diminished seven days after stopping omeprazole on Day 14.

Bacteroidetes phylum was associated with the Day 14 group when findings from that day were compared to those from Day 1 and Day 7 (data not shown).