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

Childhood stunting, defined as low height-for-age, is a significant global health problem with irreversible consequences for physical and cognitive development. The first 1000 days of life are crucial for growth, and stunting during this period can lead to long-term health issues, reduced earning potential, and a perpetuation of the poverty cycle. Approximately 20-30% of stunting occurs in utero, influenced by maternal health and fetal development. Stunting is frequently accompanied by other forms of malnutrition, including wasting (low weight-for-height) and underweight (low weight-for-age), as well as micronutrient deficiencies. The paper focuses on the role of parasitic infections as a contributing factor to childhood stunting, highlighting the lack of sufficient nutritious food for mothers and children in pre- and postnatal periods as a significant contributing factor. Parasitic infections exacerbate the problem by reducing food intake (due to illness, pain, and appetite suppression), inducing diarrhoea, and impairing nutrient absorption. The authors propose to explore the multiple mechanistic pathways by which parasitic infections contribute to this significant global health problem.

The authors review existing literature on the association between parasitic infections and childhood stunting. They cite studies demonstrating the impact of parasites on appetite regulation (e.g., through altered leptin levels), the effects of parasite-induced diarrhoea on nutrient absorption and IGF-1 levels, and the contribution of environmental enteric dysfunction (EED) to impaired nutrient absorption and inflammation. Furthermore, the literature review touches upon the role of the gut microbiota in stunting, highlighting studies that associate specific microbial profiles with malnutrition and EED. Existing studies on the effects of parasitic infections on anaemia and immune activation are also incorporated. Finally, the literature review includes studies that have explored the role of epigenetic modifications in mediating the effects of malnutrition and infection on growth and development. This review establishes the existing knowledge base and highlights the gaps that need further research.

This is an opinion paper, not an empirical study. The methodology involves a comprehensive review of the existing literature on the relationship between parasitic infections and childhood stunting. The authors systematically searched and analyzed relevant studies to identify key mechanistic pathways linking parasitic infections to stunting. The pathways explored include: A. Nutritional deficiencies: The direct impact of parasitic infections on nutrient intake and utilization. B. Diarrhoea: The effects of parasite-induced diarrhoea on nutrient absorption and growth. C. Environmental enteric dysfunction (EED): The role of EED, characterized by gut inflammation and impaired intestinal barrier function, in exacerbating malnutrition and stunting. D. Gut microbiota dysbiosis: The interplay between parasitic infections and the gut microbiota in influencing stunting. E. Chronic immune activation and systemic inflammation: The metabolic costs of chronic inflammation due to parasitic infections. F. Anaemia: The contribution of parasite-induced anaemia to impaired growth. G. Epigenetic alterations: The potential role of epigenetic changes in mediating the long-term effects of parasitic infections on growth and development. The authors synthesize information from different studies to illustrate the intricate and interconnected nature of these pathways and the challenges in establishing clear causality. The paper relies heavily on the existing body of research and aims to provide a framework for future research.

The paper doesn't present original key findings but synthesizes existing literature to outline several potential pathways linking parasitic infections to childhood stunting. 1. **Nutritional deficiencies:** Parasites reduce nutrient intake through illness, pain, and appetite suppression (via altered satiety hormone levels). 2. **Diarrhoea:** Parasite-induced diarrhoea impairs nutrient absorption and digestion, directly impacting growth. While not always a sufficient explanation, recurrent severe diarrhoea significantly reduces growth. 3. **Environmental enteric dysfunction (EED):** EED, characterized by inflammation and damaged intestinal lining, severely impairs nutrient absorption, exacerbating malnutrition and contributing to stunting. 4. **Gut microbiota dysbiosis:** Specific bacterial profiles are associated with stunting and EED, potentially creating a vicious cycle where an immature microbiota increases susceptibility to parasitic infection, which in turn further disrupts the microbiota. Studies show potential for microbiota-targeted therapies. 5. **Chronic immune activation and systemic inflammation:** Fighting infection is metabolically costly, diverting nutrients from growth. Studies show associations between immune responses to parasites and stunted growth. 6. **Anaemia:** Parasites often cause anaemia, further limiting growth due to reduced oxygen-dependent energy metabolism. Maternal anaemia can also affect the quality and quantity of breast milk. 7. **Epigenetic alterations:** Epigenetic changes induced by parasitic infections and malnutrition may have long-term consequences for growth and development, potentially spanning generations. Studies show epigenetic changes in immune cells following infection, potentially influencing immune function and growth. The intergenerational effects of parasitic infections and their impact on the epigenome remain largely unexplored.

The paper's discussion section emphasizes the complexity of the relationship between parasitic infections and childhood stunting, highlighting the multiple interacting pathways and the difficulty in establishing direct causality. The authors acknowledge that stunting may be a consequence of multiple interacting factors, rather than solely a direct result of parasitic infection. The authors highlight the need for large-scale longitudinal studies that incorporate detailed assessments of parasite burden, nutrient intake, gut microbiota composition, immune function, and epigenetic changes to better understand the interplay of these factors. The authors also discuss the need to consider the timing of infections, as well as the potential for both short-term and long-term consequences of parasitic infections on childhood growth.

Childhood stunting is a multifaceted problem, and addressing its underlying causes requires a holistic approach. Parasitic infections contribute significantly through several interconnected mechanisms. Further research, particularly longitudinal studies, is crucial to unravel the complex interactions between parasites, nutrition, the gut microbiota, immune responses, and epigenetics to develop effective interventions. Specifically, identifying the most impactful parasite species, the critical period of infection, and the intergenerational effects of parasitic infections warrant attention. Future research should also focus on testing the effectiveness of interventions targeted at addressing the multiple pathways discussed.

As an opinion paper based on a review of existing literature, the study's limitations stem from the inherent limitations of the studies it reviews. Heterogeneity in study designs, populations, and methodologies limits the ability to draw definitive causal conclusions. The lack of large, longitudinal studies with comprehensive data on all relevant factors hampers a complete understanding of the complex interplay of factors involved in childhood stunting. The reliance on mostly observational studies limits the ability to determine causality definitively.