# The putative role of the microbiota in the development of neuropsychiatric disorders following early childhood malnutrition

**Authors:** Yahya Jama, Waliul Khan, Stephen M. Collins

PMC · DOI: 10.1080/19490976.2026.2643373 · 2026-03-17

## TL;DR

This paper explores how early childhood malnutrition may lead to brain and mental health issues later in life by affecting gut bacteria and related biological processes.

## Contribution

The paper highlights the microbiota as a biologically plausible intermediary in the link between early childhood malnutrition and neuropsychiatric disorders.

## Key findings

- ECM is associated with delayed microbiota maturation and reduced diversity, including loss of key microbial taxa.
- Microbial changes coincide with metabolic, immune, and barrier dysfunctions that may affect brain development.
- Animal studies show that early microbiota disruption can cause lasting neurodevelopmental and behavioral changes.

## Abstract

Early childhood malnutrition (ECM) is robustly associated with increased risk of cognitive impairment and neuropsychiatric disorders across the lifespan, yet the biological mechanisms underlying this vulnerability remain incompletely defined. Accumulating clinical evidence indicates that ECM is associated with delayed maturation and reduced diversity of the intestinal microbiota, including depletion of taxa involved in short-chain fatty acid production and complex carbohydrate fermentation. These microbial alterations coincide with broader metabolic, immune, and barrier dysfunctions – such as reduced availability of neuroactive metabolites, low-grade inflammation, and impaired intestinal and vascular integrity – that plausibly intersect with critical processes in brain development. Experimental studies in animal models demonstrate that perturbation of microbiota-derived signaling during sensitive early periods is sufficient to induce lasting neurodevelopmental and behavioral changes, providing proof of concept for a causal role. However, in human populations, the microbiota remains best viewed as a biologically plausible intermediary rather than a proven determinant of outcome. Future progress will require integrative longitudinal studies and developmentally timed interventions to test whether restoration of microbiota function can modify neurodevelopmental trajectories. Clarifying these relationships has important implications for understanding the long-term consequences of early nutritional adversity and for identifying preventive strategies in settings where ECM remains prevalent.

## Full-text entities

- **Genes:** Ddit4 (DNA-damage-inducible transcript 4) [NCBI Gene 74747] {aka 5830413E08Rik, REDD1, Rtp801, dig2}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, Oxt (oxytocin) [NCBI Gene 18429] {aka OT, Oxy}, Gpr34 (G protein-coupled receptor 34) [NCBI Gene 23890] {aka Lypsr1}, FFAR2 (free fatty acid receptor 2) [NCBI Gene 2867] {aka FFA2R, GPR43}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, FFAR3 (free fatty acid receptor 3) [NCBI Gene 2865] {aka FFA3R, GPR41}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, Crp (C-reactive protein, pentraxin-related) [NCBI Gene 12944], AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}
- **Diseases:** starvation (MESH:D013217), growth impairment (MESH:D006130), inflammation (MESH:D007249), failure (MESH:D051437), ADHD (MESH:D001289), edema (MESH:D004487), anxiety (MESH:D001007), traumatic brain injury (MESH:D000070642), impairments in memory, attention (MESH:D008569), diarrheal (MESH:D004403), lean body mass gain (MESH:D013851), Environmental Enteric Dysfunction (MESH:D004751), immune dysregulation (OMIM:614878), neuropsychiatric problems (MESH:D019973), neural deficits (MESH:D009461), reduced communication and motor skills (MESH:D019957), mucosal dysfunction (MESH:D052016), weight loss (MESH:D015431), macro- and micro-nutrient deficiencies (MESH:C536681), hepatic growth hormone resistance (MESH:D046150), brain dysfunction (MESH:D001927), wasting (MESH:D019282), AM (MESH:D000067011), metabolic abnormalities (MESH:D008659), ASD (MESH:D000067877), fat loss (MESH:D004620), DOHaD (OMIM:603663), neurodegenerative and cognitive disorders (MESH:D019636), kwashiorkor (MESH:D007732), neurodevelopmental impairment (MESH:D009422), developmental impairments (MESH:D007805), immunodeficiency (MESH:D007153), neuroinflammation (MESH:D000090862), and behavioral vulnerability (MESH:D001523), neurobehavioral delays (MESH:D019954), muscle wasting (MESH:D009133), cognitive decline (MESH:D003072), Parkinson's disease (MESH:D010300), affective disorders (MESH:D019964), Protein-energy deficiency (MESH:D011502), dysbiosis (MESH:D064806), gastrointestinal side effects (MESH:D064420), depression (MESH:D003866), antisocial personality disorder (MESH:D000987), deaths (MESH:D003643), Malnutrition (MESH:D044342), enteropathy (MESH:C538273), intestinal problems (MESH:D007410), Autism (MESH:D001321), infection (MESH:D007239), trauma (MESH:D014947), developmental delay (MESH:D002658), schizophrenia (MESH:D012559), dyslipidemia (MESH:D050171)
- **Chemicals:** acetate (MESH:D000085), Butyrate (MESH:D002087), SCFA (MESH:D005232), carbohydrate (MESH:D002241), ATP (MESH:D000255), vitamin D (MESH:D014807), lipopolysaccharide (MESH:D008070), kynurenine (MESH:D007737), oligosaccharides (MESH:D009844), phospholipids (MESH:D010743), bile acid (MESH:D001647), amino acid (MESH:D000596), lysophosphatidylcholine (MESH:D008244), sphingolipid (MESH:D013107), indoles (MESH:D007211), PUFA (MESH:D005231), glycosphingolipids (MESH:D006028), DHA (MESH:D004281), ceramides (MESH:D002518), serotonin (MESH:D012701), tryptophan (MESH:D014364), lysophospholipids (MESH:D008246), Lipid (MESH:D008055), essential amino acids (MESH:D000601), zinc (MESH:D015032), propionate (MESH:D011422), sphingomyelin (MESH:D013109), iron (MESH:D007501), ketone body (MESH:D007657), oxygen (MESH:D010100), fatty acid (MESH:D005227), ECM (-)
- **Species:** Veillonella (genus) [taxon 29465], Bacteroides fragilis (species) [taxon 817], Streptococcus salivarius (species) [taxon 1304], Akkermansia (genus) [taxon 239934], Sutterella (genus) [taxon 40544], Alistipes (genus) [taxon 239759], Eubacteriales (order) [taxon 186802], Streptococcus mitis (species) [taxon 28037], Bifidobacterium longum (species) [taxon 216816], Escherichia coli (E. coli, species) [taxon 562], Collinsella (genus) [taxon 102106], Limosilactobacillus reuteri (species) [taxon 1598], Fusobacterium periodonticum (species) [taxon 860], Ligilactobacillus salivarius (species) [taxon 1624], Enterococcus (genus) [taxon 1350], Agathobaculum (genus) [taxon 2048137], Oscillibacter (genus) [taxon 459786], Bacteroides ovatus (species) [taxon 28116], Streptococcus oralis (species) [taxon 1303], Clostridia (class) [taxon 186801], Faecalibacterium prausnitzii (species) [taxon 853], Eubacterium (genus) [taxon 1730], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Eggerthella lenta (species) [taxon 84112], Fusicatenibacter saccharivorans (species) [taxon 1150298], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Rothia mucilaginosa (species) [taxon 43675], Lactobacillus acidophilus (species) [taxon 1579], Roseburia (genus) [taxon 841], Segatella copri (species) [taxon 165179], Homo sapiens (human, species) [taxon 9606], Limosilactobacillus mucosae (species) [taxon 97478], gut metagenome (species) [taxon 749906], Haemophilus (genus) [taxon 724], [Clostridium] symbiosum (species) [taxon 1512], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mediterraneibacter gnavus (species) [taxon 33038], Mus musculus (house mouse, species) [taxon 10090], Rodentia (rodent, order) [taxon 9989], Anaerostipes (genus) [taxon 207244]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13003873/full.md

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Source: https://tomesphere.com/paper/PMC13003873