Parasites and childhood stunting -a mechanistic interplay with nutrition, anaemia, gut health, microbiota, and epigenetics

The paper addresses how parasitic infections may contribute to childhood stunting, especially within the first 1000 days from conception to age two, a critical window after which stunting is largely irreversible. Stunting is linked to impaired organ and immune development, higher infection susceptibility, increased morbidity and mortality, long-term risks of obesity and noncommunicable diseases, adverse pregnancy outcomes for women, intergenerational effects, and reduced neurocognitive development with lifelong socioeconomic consequences. The authors frame parasites as key enteropathogens potentially acting through multiple, interlinked pathways—nutrition, diarrhoea and environmental enteric dysfunction (EED), gut permeability and inflammation, microbiota immaturity, systemic immune activation and IGF-1 suppression, anaemia, and epigenetic alterations—to influence linear growth.

The article synthesizes evidence from epidemiologic studies, birth cohorts, mechanistic and animal models, and clinical trials. It reviews: (1) nutrition-related pathways, including appetite alterations and nutrient intake deficits associated with gastrointestinal parasitoses; (2) diarrhoea’s mixed impact on linear growth (e.g., GEMS findings vs. catch-up growth observations), noting that parasitic infection in early life affects height even when adjusting for diarrhoea; (3) EED features (villous atrophy, crypt hyperplasia, increased permeability) and links to parasitic infections (e.g., Giardia, Entamoeba histolytica) and growth outcomes; (4) gut microbiota immaturity signatures in malnourished/stunted children and their potential causal role (mouse fecal transplant studies), and documented parasite–microbiota interactions; (5) systemic inflammation and immune activation diverting energy from growth and suppressing IGF-1; (6) parasite-induced anaemia via multiple mechanisms, including blood loss, haemolysis, hepcidin-driven iron sequestration, and hypersplenism; and (7) emerging evidence that parasitic infections modulate host epigenetics with plausible implications for growth and intergenerational effects. The review highlights heterogeneity and gaps, especially regarding causality, timing, and interactions among pathways and co-infections.

Opinion/narrative review synthesizing existing literature across epidemiologic, clinical, mechanistic, and experimental studies to propose and discuss potential causal pathways from parasitic infection to childhood stunting. No primary data collection or formal systematic/meta-analytic methods are reported.

- Multiple mechanistic pathways may link parasitic infections to stunting, often interacting in cycles rather than a single linear route (Pathways A–G): appetite/nutrition, diarrhoea/EED, gut permeability/inflammation, microbiota dysbiosis/immaturity, systemic inflammation and IGF-1 suppression, anaemia, and epigenetic changes. - Global burden context: in 2020 an estimated 149.2 million (22%) under-5 children were stunted; 45.4 million (6.7%) were wasted; 12.6% underweight; and in 2019, 24.4% had micronutrient deficiencies. - Diarrhoea–growth links: GEMS reported lower HAZ in infants two months after diarrhoeal episodes vs. controls; five or more episodes in the first two years may account for ~25% of stunting, though other studies show limited impact or catch-up growth. - EED: associated with villous atrophy, crypt hyperplasia, inflammation and increased permeability, leading to impaired nutrient absorption; biomarker evidence suggests inflammation is associated with reduced linear growth (e.g., upper-quartile intestinal inflammation biomarkers linked to 1.08 cm less growth over 6 months). Associations seen between faecal A1AT, current helminth infection, and stunting in some cohorts. - Microbiota: malnourished/stunted children show immature microbiota profiles; specific taxa shifts (e.g., increased Enterobacteriaceae, Veillonella, Streptococcus, Rothia; reduced butyrate-producing Clostridia). Mouse models support a causal role for microbiota from stunted/EED donors in transmitting phenotypes. Early clinical evidence suggests microbiota-directed therapeutics (e.g., Bifidobacterium infantis) can increase weight-for-age in malnourished infants. - Parasite–microbiota interactions: co-occurrence patterns and competitive/immune-mediated effects are reported, but findings can be context- and species-specific (e.g., mixed associations between Enterobacteriaceae and Giardia across studies). - Systemic inflammation and immune activation: energetically costly immune responses (e.g., elevated IgE) are associated with growth reductions; inflammatory pathways suppress IGF-1 (GH resistance), contributing to growth plate effects and reduced linear growth; EED and inflammation together predicted up to 55% of growth faltering in a Gambian infant study. - Amino acid depletion: parasites can consume key amino acids (e.g., Giardia uses arginine), and immune demand increases amino acid requirements, impairing barrier repair and growth (low serum glutamine/arginine associated with reduced growth and barrier function). - Anaemia: parasites (helminths, malaria, leishmania, babesiosis) cause anaemia via blood loss, haemolysis, hepcidin-driven iron sequestration, reduced erythropoiesis, and hypersplenism; malaria is causally linked to increased stunting risk. Maternal parasite-induced anaemia may impair breastfeeding quantity/quality. - Epigenetics: DNA methylation is implicated in growth regulation and programming effects of prenatal malnutrition; parasites modify host epigenetic profiles related to immunity (e.g., helminth-induced methylation signatures; maternal schistosomiasis affecting offspring T-cell differentiation). Direct links between parasite–epigenetic changes and stunting remain to be established.

The synthesis indicates that parasitic infections can influence child linear growth through interconnected pathways: reduced nutrient intake/absorption, EED-driven gut barrier dysfunction, systemic inflammation with IGF-1 suppression, anaemia-mediated hypoxia/iron restriction, microbiota immaturity/dysbiosis, and epigenetic modulation. These mechanisms can be synergistic and cyclical, especially during the first 1000 days when growth and microbial/immune development are highly plastic. Evidence from cohorts, biomarker studies, and animal models supports plausibility, but heterogeneity and confounding (e.g., WASH, diet, co-infections, socioeconomic factors) complicate causal inference. Recognizing these interactions is crucial for designing integrated interventions (nutrition, deworming, infection control, microbiota-directed therapies, and maternal health strategies) and for prioritizing longitudinal and interventional studies to clarify timing, species-specific effects, and mediating pathways.

Parasitic infections likely contribute to childhood stunting via multiple, interlinked mechanisms encompassing nutrition, EED, microbiota alterations, systemic inflammation/IGF-1 suppression, anaemia, and epigenetic regulation. Given heterogeneous and sometimes contradictory findings, establishing causality requires robust longitudinal and interventional research that jointly measures parasite burden, microbiota development, EED biomarkers, immune/metabolic markers, and growth outcomes. Future work should: identify parasite species with the greatest stunting impact; determine critical windows of susceptibility within the first 1000 days; elucidate helminth-associated immune modulation; clarify parasite–microbiota interactions along the gut; assess epigenetic alterations in relevant tissues; evaluate maternal infection effects mediated by microbiota and epigenome; and leverage multicountry randomized trials (e.g., deworming in pregnancy/early childhood) to test impacts on linear growth.

- Narrative/opinion synthesis without a formal systematic review or meta-analysis. - Heterogeneity in study designs, populations, diagnostics, and outcome measures; potential confounding by WASH, nutrition, and co-infections. - Limited direct human causal evidence linking specific parasites to stunting via defined mechanisms; many findings are associative or from animal models. - EED lacks standardized diagnostic criteria; reliance on invasive biopsies or imperfect biomarkers hampers inference. - Most microbiota data derive from stool, which may not reflect small intestinal communities where absorption occurs. - Limited data on timing, dose–response, and species-specific effects; few large longitudinal cohorts integrating parasites, microbiota, EED, immune/metabolic markers, and growth. - Epigenetic evidence linking parasitic infection to growth outcomes in humans is preliminary; tissue-specific effects remain unclear.