The link between malnutrition, immunity, infection, inflammation and growth: New pathological mechanisms

Primary (acute and chronic) malnutrition is still prevalent in developing countries because of inadequate nutrition and poor sanitation caused by social, economic, and environmental factors. In addition, acute malnutrition can occur secondary to an underlying disease that interferes with the intake, digestion, absorption, or assimilation of different nutrients increases nutrient loss, and/or increases energy expenditure. Immune dysfunction and infection are tightly linked to and actively contribute to the metabolic and hormonal dysregulation as well as to the progression of malnutrition.

An inadequate dietary intake of macro-and micronutrients is proposed to adversely affect local intestinal and systemic immunity, intestinal mucosal integrity, and the interaction between host defense and pathogens. Lowered immunity, mucosal damage, recurrent and prolonged infections, and gut inflammation negatively affect the malnourished child growth in weight and height as well as psycho-mental development in endemic areas. Both infection and inflammation aggressively contribute to malnutrition triggering a vicious cycle. Almost all infantile and childhood malnutrition in endemic settings (unlike anorexia nervosa) results from deficient diet, infection, inflammation, and intestinal dysfunction (most children in endemic areas have environmental enteric dysfunction (EED), often with high fecal inflammatory markers. We highlight gaps in our understanding of the current interaction among immune dysfunction, infection, and inflammation in malnourished children, and evaluate the possible responsibility of pro-inflammatory cytokines in the initiation and progression of severe malnutrition. Breach of the malicious cycle between malnutrition and infection/inflammation requires innovative interferences to recover the immune defense and enforce host defense against pathogens and reduce morbidity and mortality.