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

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Tesfaw G, Siraj DS, Abdissa A, Jakobsen RR, Johansen ØH, Zangenberg M, Hanevik K, Mekonnen Z, Langeland N, Bjørang O, Safdar N, Mapes AC, Kates A, Krych L, Castro-Mejía JL, Nielsen DS
Journal
Nature communications
Year
2024
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


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/04

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

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
healthy 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
Children under 5 years with Acute(AD) and Prolonged or persistent diarrhea(ProPD)
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).
raw counts
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
age, time, region of residence, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, time, breast feeding, education level, geographic area, sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/04

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Source: Supplementary Table 1

Description: This is a box plot that compares the relative abundance of bacterial taxa in Ethiopian children with diarrhea (both acute and prolonged/persistent) to that in non-diarrheal controls.

Abundance in Group 1: increased abundance in Diarrhea

NCBI Quality ControlLinks
Escherichia sp.
Haemophilus parainfluenzae
Ligilactobacillus ruminis
Veillonella dispar
unclassified Bacteria
unclassified Campylobacter
unclassified Enterobacteriaceae
unclassified Streptococcus

Revision editor(s): Cateline Ouma, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/09

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Source: Figure 4a, Supplementary Table 1

Description: This is a box plot that shows the differential abundance between children with diarrhea (AD and ProPD) and healthy controls.

Abundance in Group 1: decreased abundance in Diarrhea

NCBI Quality ControlLinks
Bacteroides fragilis
Dialister succinatiphilus
Faecalibacterium prausnitzii
Gemmiger formicilis
Ligilactobacillus ruminis
Segatella copri
Succinivibrio dextrinosolvens
unclassified Coriobacteriaceae
unclassified Lachnospiraceae
unclassified Lactobacillus
unclassified Mitsuokella
unclassified Prevotellaceae

Revision editor(s): Cateline Ouma, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/09

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Controls
Group 1 name Corresponds to the case (exposed) 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
Children under 5 years with acute diarrhea that lasted less than 7 days prior to enrollment into the study
Group 1 sample size Number of subjects in the case (exposed) group
554

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/09

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Source: Figure 4b, Supplementary Table 2

Description: A box plot comparing the relative abundance of taxa in children with acute diarrhea (AD) and non-diarrheal controls

Abundance in Group 1: increased abundance in Acute Diarrhea

NCBI Quality ControlLinks
Escherichia sp.
Haemophilus parainfluenzae
Veillonella dispar
unclassified Bacteria
unclassified Bifidobacterium
unclassified Campylobacter
unclassified Streptococcus
Ligilactobacillus ruminis

Revision editor(s): Cateline Ouma, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/09

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Source: Figure 4b, Supplementary Table 2

Description: A box plot comparing the relative abundance of taxa in children with acute diarrhea (AD) and non-diarrheal controls

Abundance in Group 1: decreased abundance in Acute Diarrhea

NCBI Quality ControlLinks
Bacteroides fragilis
Dialister succinatiphilus
Faecalibacterium prausnitzii
Gemmiger formicilis
Segatella copri
Succinivibrio dextrinosolvens
unclassified Coriobacteriaceae
unclassified Lachnospiraceae
unclassified Lactobacillus
unclassified Mitsuokella

Revision editor(s): Cateline Ouma, Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/10

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Prolonged or Persistent Diarrhea
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A combination of children whose diarrhea lasted for 7-13 days (Prolonged Diarrhea) and those whose diarrhea lasted for 14 days or longer (Persistent Diarrhea).
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, time, breast feeding, geographic area, sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/11

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Rahila

Source: Figure 4c, Supplementary table 3

Description: DESEq2 differential abundance of taxa in children with prolonged or persistent diarrhea (ProPD) and non-diarrheal controls.

Abundance in Group 1: increased abundance in Prolonged or Persistent Diarrhea

NCBI Quality ControlLinks
Escherichia sp.
Limosilactobacillus mucosae
Veillonella dispar
unclassified Bacteria
unclassified Campylobacter
unclassified Streptococcus
Mediterraneibacter gnavus

Revision editor(s): Cateline Ouma, Rahila

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/11

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Rahila, Peace Sandy

Source: Figure 4c, Supplementary table 3

Description: DESeq2 analysis of differentially abundant taxa

Abundance in Group 1: decreased abundance in Prolonged or Persistent Diarrhea

NCBI Quality ControlLinks
Anaerostipes hadrus
Bacteroides fragilis
Dialister succinatiphilus
Faecalibacterium prausnitzii
Gemmiger formicilis
Leyella stercorea
Roseburia inulinivorans
unclassified Bacteroides
unclassified Coriobacteriaceae
unclassified Mitsuokella
unclassified Clostridium

Revision editor(s): Cateline Ouma, Rahila, Peace Sandy

Experiment 4


Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/15

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

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
Combined cases of prolonged diarrhea (7-13 days) and persistent diarrhea (≥14 days)
Group 0 sample size Number of subjects in the control (unexposed) group
554

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, time, breast feeding, education level, geographic area, sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/15

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma

Source: Figure 4d, Supplementary Table 4

Description: A box plot showing differential abundance of taxa in ProPD cases versus AD cases.

Abundance in Group 1: increased abundance in Prolonged or Persistent Diarrhea

NCBI Quality ControlLinks
unclassified Lactobacillus

Revision editor(s): Cateline Ouma

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-29

Curated date: 2024/10/15

Curator: Cateline Ouma

Revision editor(s): Cateline Ouma, Peace Sandy

Source: Figure 4d, Supplementary Table 4

Description: A box plot comparing the relative abundance of taxa in ProPD cases versus AD cases

Abundance in Group 1: decreased abundance in Prolonged or Persistent Diarrhea

NCBI Quality ControlLinks
Anaerostipes hadrus
Faecalibacterium prausnitzii
unclassified Coriobacteriaceae
unclassified Bacteroides

Revision editor(s): Cateline Ouma, Peace Sandy