Gut microbiota differences in stunted and normal-lenght children aged 36-45 months in East Nusa Tenggara, Indonesia

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Surono IS, Popov I, Verbruggen S, Verhoeven J, Kusumo PD, Venema K
Journal
PloS one
Year
2024
The role of the gut microbiota in energy metabolism of the host has been established, both in overweight/obesity, as well as in undernutrition/stunting. Dysbiosis of the gut microbiota may predispose to stunting. The aim of this study was to compare the gut microbiota composition of stunted Indonesian children and non-stunted children between 36 and 45 months from two sites on the East Nusa Tenggara (ENT) islands. Fecal samples were collected from 100 stunted children and 100 non-stunted children in Kupang and North Kodi. The gut microbiota composition was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. Moreover, fecal SCFA concentrations were analyzed. The microbiota composition was correlated to anthropometric parameters and fecal metabolites. The phyla Bacteroidetes (Bacteroidota; q = 0.014) and Cyanobacteria (q = 0.049) were significantly higher in stunted children. Three taxa at genus levels were consistently significantly higher in stunted children at both sampling sites, namely Lachnoclostridium, Faecalibacterium and Veillonella (q < 7 * 10-4). These and 9 other taxa positively correlated to the z-score length-for-age (zlen), while 11 taxa negatively correlated with zlen. Several taxa also correlated with sanitary parameters, some of which were also significantly different between the two groups. All three fecal SCFA concentrations (acetate, propionate and butyrate) and their total were lower in stunted children compared to non-stunted children, although not significant for butyrate, indicating lower energy-extraction by the gut microbiota. Also, since SCFA have been shown to be involved in gut barrier function, barrier integrity may be affected in the stunted children. It remains to be seen if the three taxa are involved in stunting, or are changed due to e.g. differences in diet, hygiene status, or other factors. The observed differences in this study do not agree with our previous observations in children on Java, Indonesia. There are differences in infrastructure facilities such as clean water and sanitation on ENT and Java, which may contribute to the differences observed. The role of the gut microbiota in stunting therefore requires more in depth studies. Trial registration: the trial was registered at ClinicalTrials.gov with identifier number NCT05119218.

Experiment 1


Needs review

Curated date: 2025/02/22

Curator: An05hka

Revision editor(s): An05hka

Subjects

Location of subjects
Indonesia
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
Short stature Decreased body height,Height less than 3rd percentile,Short stature,Small stature,Stature below 3rd percentile,short stature
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Length children
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stunted Length children
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Stunted length children aged 36–45 months
Group 0 sample size Number of subjects in the control (unexposed) group
100
Group 1 sample size Number of subjects in the case (exposed) group
100

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
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

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Needs review

Curated date: 2025/02/23

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 4.

Description: Boxplots of the 3 taxa at genus level that were significantly different between non-stunted and stunted children.

Abundance in Group 1: increased abundance in Stunted Length children

NCBI Quality ControlLinks
Faecalibacterium
Lachnoclostridium
Veillonella

Revision editor(s): An05hka

Experiment 2


Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Length children in Kupang
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stunted Length children in Kupang
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Stunted length children aged 36–45 months from Kupang
Group 0 sample size Number of subjects in the control (unexposed) group
50
Group 1 sample size Number of subjects in the case (exposed) group
50

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 4.

Description: Boxplots of the 3 taxa at genus level that were significantly different (Kruskal-Wallis analysis, with Benjamini-Hochberg FDR correction) between non-stunted and stunted children of Kupang.

Abundance in Group 1: increased abundance in Stunted Length children in Kupang

NCBI Quality ControlLinks
Faecalibacterium
Veillonella
Lachnoclostridium

Revision editor(s): An05hka

Experiment 3


Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Length children from North Kodi
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stunted Length children from North Kodi
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Stunted length children aged 36–45 months from North Kodi

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 4.

Description: Boxplots of the 3 taxa at genus level that were significantly different (Kruskal-Wallis analysis, with Benjamini-Hochberg FDR correction) between non-stunted and stunted children from North Kodi

Abundance in Group 1: increased abundance in Stunted Length children from North Kodi

NCBI Quality ControlLinks
Veillonella
Faecalibacterium
Lachnoclostridium

Revision editor(s): An05hka

Experiment 4


Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Length children
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stunted Length children
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Stunted length children aged 36–45 months
Group 0 sample size Number of subjects in the control (unexposed) group
100
Group 1 sample size Number of subjects in the case (exposed) group
100

Lab analysis

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No


Signature 1

Needs review

Curated date: 2025/02/24

Curator: An05hka

Revision editor(s): An05hka

Source: Table 3.

Description: Gut microbiota composition at the phylum level

Abundance in Group 1: increased abundance in Stunted Length children

NCBI Quality ControlLinks
Bacteroidia
Cyanobacteriota

Revision editor(s): An05hka

Experiment 5


Needs review

Curated date: 2025/03/06

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body weight weight,Body weight,body weight
Group 0 name Corresponds to the control (unexposed) group for case-control studies
low Weight
Group 1 name Corresponds to the case (exposed) group for case-control studies
High Weight
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children with high weight aged 36-45 months

Lab analysis

Statistical Analysis

Statistical test
Spearman Correlation
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes


Signature 2

Needs review

Curated date: 2025/03/10

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 6 A , weight

Description: Heatmap of the taxa at genus level that were different (q < 0.05) when correlated by Spearman correlation analysis to the weight. Blue: Positive correlation; red: Negative correlation

Abundance in Group 1: decreased abundance in High Weight

NCBI Quality ControlLinks
Ruminococcaceae D5 unculturedRuminococcaceae D5 uncultured

Revision editor(s): An05hka

Experiment 6


Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body height height,Body height,body height
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low Height
Group 1 name Corresponds to the case (exposed) group for case-control studies
High Height
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children with high Height aged 36-45 months

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 6A. ,height

Description: Heatmap of the taxa at genus level that were different (q < 0.05) when correlated by Spearman correlation analysis to the Height. Blue: Positive correlation; red: Negative correlation.

Abundance in Group 1: increased abundance in High Height

NCBI Quality ControlLinks
Akkermansia
Alistipes
Anaerobutyricum hallii
Anaerostipes
Bacteroides
Bifidobacterium
Blautia
Carnobacteriaceae
Dorea
Eubacterium ventriosum
Flavonifractor
Fusicatenibacter
Gemella
Holdemania
Mediterraneibacter gnavus
Megamonas
Odoribacter
Oscillospiraceae
Parabacteroides
Peptostreptococcaceae
Subdoligranulum
Thomasclavelia
Ruminiclostridium 5Ruminiclostridium 5
Ruminococcaceae UCG-004Ruminococcaceae UCG-004
Ruminococcaceae UCG-013Ruminococcaceae UCG-013
Family XIII AD3011Family XIII AD3011

Revision editor(s): An05hka

Signature 2

Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 6A. ,height

Description: Heatmap of the taxa at genus level that were different (q < 0.05) when correlated by Spearman correlation analysis to the Height. Positive correlation; red: Negative correlation

Abundance in Group 1: decreased abundance in High Height

NCBI Quality ControlLinks
Alloprevotella
Candidatus Gastranaerophilales
Catenibacterium
Dialister
Faecalibacterium
Intestinimonas
Lachnoclostridium
Lactobacillus
Sarcina
Succinivibrio
Veillonella
Prevotella 2Prevotella 2
Prevotella 9Prevotella 9
Prevotellaceae NK3b31 groupPrevotellaceae NK3b31 group
Prevotellaceae D5 unculturedPrevotellaceae D5 uncultured
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
Ruminococcaceae D5 unculturedRuminococcaceae D5 uncultured

Revision editor(s): An05hka

Experiment 7


Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body mass index BMI,Quetelet's Index,Body mass index,body mass index
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low BMI
Group 1 name Corresponds to the case (exposed) group for case-control studies
High BMI
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children with high Body Mass Index (BMI) aged 36-45 months

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified


Signature 1

Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 6A., BMI

Description: Heatmap of the taxa at genus level that were different (q < 0.05) when correlated by Spearman correlation analysis to the BMI. Positive correlation; red: Negative correlation

Abundance in Group 1: increased abundance in High BMI

NCBI Quality ControlLinks
Alloprevotella
Candidatus Gastranaerophilales
Prevotella 2Prevotella 2
Prevotella 9Prevotella 9
Prevotellaceae NK3b31 groupPrevotellaceae NK3b31 group
Prevotellaceae D5 unculturedPrevotellaceae D5 uncultured
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Lactobacillus
Sarcina
Dorea
Intestinimonas
Catenibacterium
Lachnoclostridium
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
Faecalibacterium
Dialister
Veillonella
Succinivibrio

Revision editor(s): An05hka

Signature 2

Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Source: Figure 6A., BMI

Description: Heatmap of the taxa at genus level that were different (q < 0.05) when correlated by Spearman correlation analysis to the BMI. Positive correlation; red: Negative correlation

Abundance in Group 1: decreased abundance in High BMI

NCBI Quality ControlLinks
Akkermansia
Alistipes
Anaerobutyricum hallii
Anaerostipes
Bacteroides
Bifidobacterium
Blautia
Carnobacteriaceae
Dorea
Eubacterium ventriosum
Flavonifractor
Fusicatenibacter
Gemella
Holdemania
Mediterraneibacter gnavus
Megamonas
Odoribacter
Oscillospiraceae
Parabacteroides
Peptostreptococcaceae
Subdoligranulum
Thomasclavelia
Ruminococcaceae UCG-004Ruminococcaceae UCG-004
Ruminococcaceae UCG-013Ruminococcaceae UCG-013
Ruminiclostridium 5Ruminiclostridium 5
Ruminococcaceae D5 unculturedRuminococcaceae D5 uncultured
Family XIII AD3011Family XIII AD3011

Revision editor(s): An05hka

Experiment 8


Needs review

Curated date: 2025/03/12

Curator: An05hka

Revision editor(s): An05hka

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body height height,Body height,body height
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low Height
Group 1 name Corresponds to the case (exposed) group for case-control studies
High Height
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children with high Height aged 36-45 months.
  • Data was Z-score Transformed

Lab analysis

Statistical Analysis