Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition related cognition

Study information

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study design

case-control

Citation

PMID PubMed identifier for scientific articles.

39773949

DOI Digital object identifier for electronic documents.

10.1038/s41467-024-55798-3

URI

Authors

Portlock T, Shama T, Kakon SH, Hartjen B, Pook C, Wilson BC, Bhuttor A, Ho D, Shennon I, Engelstad AM, Di Lorenzo R, Greaves G, Rahman N, Kelsey C, Gluckman PD, O'Sullivan JM, Haque R, Forrester T, Nelson CA

Journal

Nature communications

Year

2025

Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions. Survivors often suffer lasting neurocognitive consequences that impact academic performance and socioeconomic outcomes. Mechanistic understanding of the emergence of these consequences is poorly understood. Using multi-system SHAP interpreted random forest models and network analysis, we show that Moderate Acute Malnutrition (MAM) associates with enrichment of faecal Rothia mucilaginosa, Streptococcus salivarius and depletion of Bacteroides fragilis in a cohort of one-year-old children in Dhaka, Bangladesh. These microbiome changes form interconnected pathways that involve reduced plasma odd-chain fatty acid levels, decreased gamma and beta electroencephalogram power in temporal and frontal brain regions, and reduced vocalization. These findings support the hypothesis that prolonged colonization by oral commensal species delay gut microbiome and brain development. While causal links require empirical validation, this study provides insights to improve interventions targeting MAM-associated neurodevelopmental deficits.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-29

Curated date: 2025/03/20

Curator: D-coder111

Revision editor(s): D-coder111

Subjects

Location of subjects: Bangladesh

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: Malnutrition Lack of food,Malnutrition,malnutrition

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Well-nourished infants

Group 1 name Corresponds to the case (exposed) group for case-control studies: MAM (Moderate Acute Malnutrition) infants

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Infants aged 12 ± 1 months diagnosed with Moderate Acute Malnutrition (Weight-for-Length Z-score between -2 and -3 SD)

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: 159

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: 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).: relative abundances

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.25

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: Confounders controlled for: "delivery mode" 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.delivery mode, Confounders controlled for: "child sex" 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.child sex, Confounders controlled for: "duration of exclusive breastfeeding" 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.duration of exclusive breastfeeding

Alpha Diversity

Pielou Quantifies how equal the community is numerically: decreased

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

Signature 1

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Revision editor(s): D-coder111, Aleru Divine

Source: Figure 1f, Supplementary Data 3

Description: This signature includes microbial taxa that were found to be significantly increased in infants with Moderate Acute Malnutrition (MAM) compared to well-nourished controls. Shotgun metagenomic sequencing of fecal samples (stool) identified an increased abundance of multiple bacterial taxa across different taxonomic levels.

The following taxa were significantly enriched in Moderate Acute Malnutrition(MAM) infants (MaAsLin2, q < 0.25).

Abundance in Group 1: increased abundance in MAM (Moderate Acute Malnutrition) infants

NCBI	Quality Control	Links
Micrococcaceae
Micrococcales
Rothia mucilaginosa
Streptococcus salivarius
unclassified viruses
Rothia

Revision editor(s): D-coder111, Aleru Divine

Signature 2

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Source: Supplementary Data 3

Description: This signature includes taxa that were found to be significantly decreased in infants with Moderate Acute Malnutrition (MAM) compared to well-nourished controls. Shotgun metagenomic sequencing of fecal samples (stool) identified a reduced abundance of Bacteroides fragilis. Statistical analysis was performed using MaAsLin2 with Benjamini-Hochberg FDR correction (q < 0.25).

Abundance in Group 1: decreased abundance in MAM (Moderate Acute Malnutrition) infants

NCBI	Quality Control	Links
Bacteroides fragilis

Revision editor(s): D-coder111