Maternal balanced energy-protein supplementation reshapes the maternal gut microbiome and enhances carbohydrate metabolism in infants: a randomized controlled trial

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Deng L, Taelman S, Olm MR, Toe LC, Balini E, Ouédraogo LO, Bastos-Moreira Y, Argaw A, Tesfamariam K, Sonnenburg ED, Hanley-Cook GT, Ouédraogo M, Ganaba R, Van Criekinge W, Huybregts L, Stock M, Kolsteren P, Sonnenburg JL, Lachat C, Dailey-Chwalibóg T
Journal
Nature communications
Year
2025
Balanced energy-protein (BEP) supplementation during pregnancy and lactation can improve birth outcomes and infant growth, with the gut microbiome as a potential mediator. The MISAME-III randomized controlled trial (ClinicalTrial.gov: NCT03533712) assessed the effect of BEP supplementation, provided during pregnancy and the first six months of lactation, on small-for-gestational age prevalence and length-for-age Z-scores at six months in rural Burkina Faso. Nested within MISAME-III, this sub-study examines the impact of BEP supplementation on maternal and infant gut microbiomes and their mediating role in birth outcomes and infant growth. A total of 152 mother-infant dyads (n = 71 intervention, n = 81 control) were included for metagenomic sequencing, with stool samples collected at the second and third trimesters, and at 1-2 and 5-6 months postpartum. BEP supplementation significantly altered maternal gut microbiome diversity, composition, and function, particularly those with immune-modulatory properties. Pathways linked to lipopolysaccharide biosynthesis were depleted and the species Bacteroides fragilis was enriched in BEP-supplemented mothers. Maternal BEP supplementation also accelerated infant microbiome changes and enhanced carbohydrate metabolism. Causal mediation analyses identified specific taxa mediating the effect of BEP on birth outcomes and infant growth. These findings suggest that maternal supplementation modulates gut microbiome composition and influences early-life development in resource-limited settings.

Experiment 1


Needs review

Curated date: 2025/04/03

Curator: Joiejoie

Revision editor(s): Joiejoie

Subjects

Location of subjects
Burkina Faso
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
Balanced reciprocal translocation Balanced reciprocal translocation,balanced reciprocal translocation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother / Infant Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother / Infant Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of taxa shared between mothers and infants across time points from third trimester, 1-2 months and 5–6 months postpartum.
Group 0 sample size Number of subjects in the control (unexposed) group
131
Group 1 sample size Number of subjects in the case (exposed) group
122

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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).
log transformation
Statistical test
ANCOM-BC2
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

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

Signature 1

Needs review

Curated date: 2025/04/07

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 3C

Description: Relative abundance of taxa shared between mothers and infants across time points

Abundance in Group 1: increased abundance in Mother / Infant Intervention

NCBI Quality ControlLinks
Bacteroides fragilis
Escherichia coli
Bacteroides fragilis ABacteroides fragilis A
Prevotella sp.900544825Prevotella sp.900544825

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/07

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 3C

Description: Relative abundance of taxa shared between mothers and infants across time points

Abundance in Group 1: decreased abundance in Mother / Infant Intervention

NCBI Quality ControlLinks
Veillonella sp.
Veillonella parvula

Revision editor(s): Joiejoie

Experiment 2


Needs review

Curated date: 2025/04/07

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of the top ten most abundant taxa species shared between mothers and infants across time points from third trimester, 1-2 months and 5–6 months postpartum.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/07

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 3D

Description: Relative abundance of the top ten most abundant species in both mother and infant samples.

Abundance in Group 1: increased abundance in Mother / Infant Intervention

NCBI Quality ControlLinks
RC9 sp. 000433355RC9 sp. 000433355
Segatella copri
Prevotella sp. 000434515Prevotella sp. 000434515
Prevotella sp. 002251295Prevotella sp. 002251295
Prevotella sp. 002299635Prevotella sp. 002299635

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/07

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 3D

Description: Relative abundance of the top ten most abundant species in both mother and infant samples.

Abundance in Group 1: decreased abundance in Mother / Infant Intervention

NCBI Quality ControlLinks
Prevotella sp.900548535Prevotella sp.900548535
C941 sp.004557565C941 sp.004557565
Prevotella sp.

Revision editor(s): Joiejoie

Experiment 3


Needs review

Curated date: 2025/04/09

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother-Tri2 Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother-Tri2 Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mothers whose stool microbiome samples were collected in the intervention group during the second trimester of pregnancy.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
22

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the second trimester (Tri2)

Abundance in Group 1: increased abundance in Mother-Tri2 Intervention

NCBI Quality ControlLinks
CAG 103 sp. 000432375CAG 103 sp. 000432375

Revision editor(s): Joiejoie

Experiment 4


Needs review

Curated date: 2025/04/09

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother-Tri3 Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother-Tri3 Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mothers whose stool microbiome samples were collected in the intervention group during the third trimester of pregnancy.
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
71

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the third trimester (Tri3)

Abundance in Group 1: increased abundance in Mother-Tri3 Intervention

NCBI Quality ControlLinks
UMGS882 sp.UMGS882 sp.
UBA1436 sp.UBA1436 sp.
Lachnospiraceae sp.Lachnospiraceae sp.

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the third trimester (Tri3)

Abundance in Group 1: decreased abundance in Mother-Tri3 Intervention

NCBI Quality ControlLinks
CAG 245 sp. 000434196CAG 245 sp. 000434196

Revision editor(s): Joiejoie

Experiment 5


Needs review

Curated date: 2025/04/09

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother-Pn12 Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother-Pn12 Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mothers whose stool microbiome samples were collected in the intervention group at 1 to 2 months postpartum.
Group 0 sample size Number of subjects in the control (unexposed) group
76
Group 1 sample size Number of subjects in the case (exposed) group
66

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the postnatal 1–2 months (Pn12)

Abundance in Group 1: increased abundance in Mother-Pn12 Intervention

NCBI Quality ControlLinks
CAG 452 sp. 000434035CAG 452 sp. 000434035
Ruminococcus C sp. 000433635Ruminococcus C sp. 000433635
CAG 533 sp.900551106CAG 533 sp.900551106

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the postnatal 1–2 months (Pn12)

Abundance in Group 1: decreased abundance in Mother-Pn12 Intervention

NCBI Quality ControlLinks
Agathobacter sp.
Agathobacter sp. 900546625Agathobacter sp. 900546625

Revision editor(s): Joiejoie

Experiment 6


Needs review

Curated date: 2025/04/09

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother-Pn56 Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother-Pn56 Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mothers whose stool microbiome samples were collected in the intervention group at 5 to 6 months postpartum.
Group 0 sample size Number of subjects in the control (unexposed) group
75
Group 1 sample size Number of subjects in the case (exposed) group
67

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the postnatal 5–6 months (Pn56)

Abundance in Group 1: increased abundance in Mother-Pn56 Intervention

NCBI Quality ControlLinks
Veillonella sp.
Zag 111 sp. 003258735Zag 111 sp. 003258735

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5A

Description: Differentially abundant taxa associated with the intervention at the postnatal 5–6 months (Pn56)

Abundance in Group 1: decreased abundance in Mother-Pn56 Intervention

NCBI Quality ControlLinks
Bacteroides fragilis
UMGS874 sp.UMGS874 sp.
UBA1232 sp. 900544815UBA1232 sp. 900544815
Phascolarctobacterium A sp. 900551335Phascolarctobacterium A sp. 900551335

Revision editor(s): Joiejoie

Experiment 7


Needs review

Curated date: 2025/04/09

Curator: Joiejoie

Revision editor(s): Joiejoie

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mother + Infant Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mother + Infant Intervention
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group received a specific treatment or dietary intervention during pregnancy.
Group 0 sample size Number of subjects in the control (unexposed) group
381
Group 1 sample size Number of subjects in the case (exposed) group
350

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5C

Description: Relative abundance of the 16 taxa that were significantly different between the intervention and control groups across all time points combined.

Abundance in Group 1: increased abundance in Mother + Infant Intervention

NCBI Quality ControlLinks
Agathobacter sp. 900546625Agathobacter sp. 900546625
Agathobacter sp.
CAG 533 sp. 900551106CAG 533 sp. 900551106
Veillonella sp.
Zag 111 sp. 003258735Zag 111 sp. 003258735
Ruminococcus C sp. 000433635Ruminococcus C sp. 000433635
CAG 103 sp. 00432375CAG 103 sp. 00432375
CAG 245 sp. 000434196CAG 245 sp. 000434196
CAG 452 sp. 000434035CAG 452 sp. 000434035

Revision editor(s): Joiejoie

Signature 2

Needs review

Curated date: 2025/04/10

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Fig. 5C

Description: Relative abundance of the 16 taxa that were significantly different between the intervention and control groups across all time points combined.

Abundance in Group 1: decreased abundance in Mother + Infant Intervention

NCBI Quality ControlLinks
Lachnospiraceae sp.Lachnospiraceae sp.
UBA1436 sp.UBA1436 sp.
UMGS882 sp.UMGS882 sp.
Bacteroides fragilis
UMGS874 sp.UMGS874 sp.
UBA1232 sp. 900544815UBA1232 sp. 900544815
Phascolarctobacterium A sp. 900551335Phascolarctobacterium A sp. 900551335

Revision editor(s): Joiejoie