Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

Severe malnutrition is associated with infections, namely lower respiratory tract infections (LRTIs), diarrhea, and sepsis, and underlies the high risk of morbidity and mortality in children under 5 years of age. Dysregulations in neutrophil responses in the acute phase of infection are speculated to underlie these severe adverse outcomes; however, very little is known about their biology in this context. Here, in a lipopolysaccharide-challenged low-protein diet (LPD) mouse model, as a model of malnutrition, we show that protein deficiency disrupts neutrophil mitochondrial dynamics and ATP generation to obstruct the neutrophil differentiation cascade. This promotes the accumulation of atypical immature neutrophils that are incapable of optimal antimicrobial response and, in turn, exacerbate systemic pathogen spread and the permeability of the alveolocapillary membrane with the resultant lung damage. Thus, this perturbed response may contribute to higher mortality risk in malnutrition. We also offer a nutritional therapeutic strategy, nicotinamide, to boost neutrophil-mediated immunity in LPD-fed mice.

Micronutrient status in children aged 6-59 months with severe wasting and/or nutritional edema: implications for nutritional rehabilitation formulations.

Undernutrition remains a global struggle and is associated with almost 45% of deaths in children younger than 5 years. Despite advances in management of severe wasting (though less so for nutritional edema), full and sustained recovery remains elusive. Children with severe wasting and/or nutritional edema (also commonly referred to as severe acute malnutrition and part of the umbrella term "severe malnutrition") continue to have a high mortality rate. This suggests a likely multifactorial etiology that may include micronutrient deficiency. Micronutrients are currently provided in therapeutic foods at levels based on expert opinion, with few supportive studies of high quality having been conducted. This narrative review looks at the knowledge base on micronutrient deficiencies in children aged 6-59 months who have severe wasting and/or nutritional edema, in addition to highlighting areas where further research is warranted (See "Future Directions" section).