Gut microbiota patterns associated with duration of diarrhea in children under five years of age in Ethiopia

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Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Dennis S. Nielsin, Getnet tesfaw, Nina langeland, abigail c. mapes, alemseged abdissa, ashley kates, dawd s. siraj, nasia safdar, zeleke mekonnen
Journal
Nature communications
Year
2024
Pages:
First page:
Keywords:
acute diarrhea, diarrhea, gut microbiota, Prolonged or persistent Diarrhea (ProPD)
Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (<7 days’ duration) is decreasing, but prolonged (7-13 days) and persistent (≥14 days of duration) diarrhea remains a massive challenge. Here, we use a case-control study to decipher if fecal gut microbiota compositional differences between Ethiopian children with acute (n=554) or prolonged/persistent (n=95) diarrhea and frequency-matched non-diarrheal controls (n=663) are linked to diarrheal etiology. We show that diarrhea cases are associated with lower bacterial diversity and enriched in Escherichia spp., Campylobacter spp., and Streptococcus spp. Further, diarrhea cases are depleted in gut commensals such as Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus, with depletion being most pronounced in prolonged/persistent cases, suggesting that prolonged duration of diarrhea is accompanied by depletion of gut commensals and that re-establishing these via e.g., microbiota-directed food supplements offer a potential treatment strategy.

Experiment 1


Needs review

Curated date: 2025/01/23

Curator:

Revision editor(s):

Subjects

Location of subjects
Ethiopia
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
Diarrhea Diarrhea,Diarrhoea,Watery stool,diarrhea
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-diarrheal controls.
Group 1 name Corresponds to the case (exposed) group for case-control studies
Diarrhea
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The aim of our study was to decipher what differentiates the GM of children with diarrhea (AD and ProPD) from healthy controls
Group 0 sample size Number of subjects in the control (unexposed) group
663
Group 1 sample size Number of subjects in the case (exposed) group
650

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
DESeq2
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: "frequency" 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.frequency
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
breast feeding

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: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4a

Description: Diarrhea cases compared with non-diarrheal controls

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
Escherichia sp.
Campylobacter sp.
Streptococcus sp.
Haemophilus parainfluenzae

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4a

Description: Diarrhea cases compared with non-diarrheal controls

Abundance in Group 1: decreased abundance in

NCBI Quality ControlLinks
Bacteroides fragilis
Prevotella corporis
Faecalibacterium prausnitzii
Dialister succinatiphilus

Revision editor(s): Miss Lulu

Experiment 2


Needs review

Curated date: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Acute Diarrhea
Group 1 sample size Number of subjects in the case (exposed) group
554

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
-V4

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
breast feeding, age, Confounders controlled for: "enrollment season" 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.enrollment season, Confounders controlled for: "enrollment site" 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.enrollment site, sex, Confounders controlled for: "WAM Index" 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.WAM Index

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: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4b and Figure 7

Description: AD cases compared with non-diarrheal controls

Abundance in Group 1: increased abundance in Acute Diarrhea

NCBI Quality ControlLinks
Escherichia sp.
Campylobacter sp.
Streptococcus sp.

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4b and Figure 7

Description: AD cases compared with non-diarrheal controls

Abundance in Group 1: decreased abundance in Acute Diarrhea

NCBI Quality ControlLinks
Faecalibacterium prausnitzii
Prevotella corporis

Revision editor(s): Miss Lulu

Experiment 3


Needs review

Curated date: 2025/01/23

Curator:

Revision editor(s):

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Prolonged or persistent Diarrhea (ProPD)
Group 1 sample size Number of subjects in the case (exposed) group
95

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, breast feeding, sex, Confounders controlled for: "enrollment season" 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.enrollment season, Confounders controlled for: "enrollment site" 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.enrollment site, Confounders controlled for: "WAM Index" 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.WAM Index

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: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4c and Figure 8

Description: ProPD cases compared with non-diarrheal controls

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
Escherichia sp.
Campylobacter sp.
Streptococcus sp.

Revision editor(s): Miss Lulu

Experiment 4


Needs review

Curated date: 2025/01/23

Curator:

Revision editor(s):

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Acute Diarrhea
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The aim of our study was to decipher what differentiates the GM of children with Prolonged or persistent diarrhea (ProPD) as compared with Acute Diarrhea
Group 0 sample size Number of subjects in the control (unexposed) group
554

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
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: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4d and Figure 9

Description: ProPD cases compared with AD cases

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
unclassified Lactobacillus
Limosilactobacillus mucosae

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/01/23

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4d and Figure 9

Description: ProPD cases compared with AD cases

Abundance in Group 1: decreased abundance in

NCBI Quality ControlLinks
Faecalibacterium prausnitzii
Akkermansia muciniphila
Anaerostipes hadrus
unclassified Coriobacteriaceae
unclassified Bacteroides

Revision editor(s): Miss Lulu