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Record W4416754273 · doi:10.1101/2025.11.26.25341054

Gut microbiome and plasma metabolic signatures of one-carbon metabolism differentiate oedematous and non-oedematous severe acute malnutrition

2025· preprint· W4416754273 on OpenAlexaff
Ruairi C. Robertson, Thaddeus J. Edens, Iman Baharmand, Natallia Varankovich, Cherlynn Dumbura, Madhuriben Panchal, Kuda Mutasa, Robert Ntozini, Bernard Chasekwa, Simutanyi Mwakamui, Freddy Francis, Ellen Besa, Thompson Runodamoto, Deophine Ngosa, Florence D. Majo, Kanekwa Zyambo, Claire D. Bourke, Sandra Rukobo, Margaret Govha, Beatrice Amadi, Kusum Nathoo, Mutsa Bwakura‐Dangarembizi, Jonathan R. Swann, Paul Kelly, Amee R. Manges, Andrew J. Prendergast

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Language
FieldNursing
TopicChild Nutrition and Water Access
Canadian institutionsBC Centre for Disease ControlUniversity of British Columbia
FundersBiotechnology and Biological Sciences Research CouncilNational Institute for Health Research Southampton Biomedical Research CentreMedical Research CouncilNational Institute for Health and Care ResearchUK Research and InnovationUNICEF
KeywordsMicrobiomeMetagenomicsMetabolismMalnutritionSevere Acute MalnutritionMetabolomicsGut microbiomeMetabolic pathwayMetabolome

Abstract

fetched live from OpenAlex

ABSTRACT Childhood severe acute malnutrition (SAM) occurs as either classical wasting (non-oedematous-SAM; NO-SAM) or with the presence of oedema (oedematous SAM; O-SAM). Both forms of SAM have distinct mortality and nutritional recovery rates, however, the underlying pathophysiology is poorly understood. We collected stool for whole metagenome shotgun sequencing and plasma for metabolic phenotyping from 238 children (79 NO-SAM, 159 O-SAM) hospitalised with complicated SAM and 141 adequately-nourished controls (ANC) from an observational, prospective cohort in Zimbabwe and Zambia. Children with SAM were followed up at 12-, 24- and 48-weeks post-discharge. During hospitalisation, there were significant alterations in taxonomic and functional microbiome diversity between O-SAM and NO-SAM. Lancefieldella parvula , a potent producer of hydrogen-sulfide from cysteine, was one of three species significantly elevated in O-SAM versus NO-SAM. Metagenomic analysis showed an overabundance of pathways involved in sulfur amino-acid and one-carbon metabolism in O-SAM compared to NO-SAM. Consistently, the sulfur amino acids cysteine and homocysteine were significantly depleted in the plasma of O-SAM versus NO-SAM, while histidine and various phosphatidylcholines were more abundant. During follow-up, O-SAM and NO-SAM microbiomes remained divergent up to 24 weeks post-discharge whilst alpha diversity recovery was delayed in NO-SAM. Plasma metabolomes also remained significantly different between O-SAM, NO-SAM and ANC throughout 48 weeks of follow-up. These findings demonstrate that distinct microbiome profiles may drive disturbance of systemic one-carbon metabolism in O-SAM and highlight persistent microbiome and metabolic dysfunction during nutritional recovery. This work supports further studies targeting the gut microbiome to correct metabolic disturbances and improve long-term clinical outcomes in complicated SAM. One Sentence Summary Children hospitalised with oedematous versus non-oedematous severe acute malnutrition have altered gut microbiomes and disrupted one-carbon metabolism, which remain distinct up to 48 weeks post-discharge.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.248
Teacher spread0.237 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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