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1.
Nat Commun ; 12(1): 6729, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795270

RESUMO

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as residence in a rural setting) may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc appears to ameliorate this effect. We suggest that the risks and benefits of micronutrient interventions may depend on eukaryotic communities, potentially exacerbated by exposure to a rural setting. Larger studies are needed to evaluate the clinical significance of these findings and their impact on health outcomes.


Assuntos
Suplementos Nutricionais , Intestinos/efeitos dos fármacos , Micronutrientes/administração & dosagem , Micobioma/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Pré-Escolar , Feminino , Fungos/classificação , Fungos/efeitos dos fármacos , Fungos/genética , Humanos , Lactente , Intestinos/microbiologia , Intestinos/parasitologia , Ferro/administração & dosagem , Masculino , Micobioma/genética , Parasitos/classificação , Parasitos/efeitos dos fármacos , Parasitos/genética , Filogenia , Estudos Prospectivos , Vitaminas/administração & dosagem , Zinco/administração & dosagem
2.
Sci Rep ; 10(1): 11235, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641735

RESUMO

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Infecções por HIV/metabolismo , Terapia Nutricional/métodos , Desnutrição Aguda Grave/terapia , Estresse Fisiológico/imunologia , Biomarcadores/sangue , Pré-Escolar , Comorbidade , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Lactente , Quênia/epidemiologia , Metabolismo dos Lipídeos/imunologia , Malaui/epidemiologia , Masculino , Estado Nutricional , Proteômica , Desnutrição Aguda Grave/sangue , Desnutrição Aguda Grave/epidemiologia , Desnutrição Aguda Grave/imunologia
3.
J Hepatol ; 65(6): 1198-1208, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27312946

RESUMO

BACKGROUND & AIMS: Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. Peroxisomes and mitochondria play key roles in various hepatic metabolic functions including lipid metabolism and energy production. To investigate the involvement of these organelles in the mechanisms underlying malnutrition-induced hepatic dysfunction we developed a rat model of malnutrition. METHODS: Weanling rats were placed on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Peroxisomal and mitochondrial structural features were characterized using immunofluorescence and electron microscopy. Mitochondrial function was assessed using high-resolution respirometry. A novel targeted quantitative proteomics method was applied to analyze 47 mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle and fatty acid ß-oxidation pathways. RESULTS: Low protein diet-fed rats developed hypoalbuminemia and hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated peroxisomal dysfunction. This was followed by changes in mitochondrial ultrastructure and increased mitochondrial content. Mitochondrial function was impaired due to multiple defects affecting respiratory chain complex I and IV, pyruvate uptake and several ß-oxidation enzymes, leading to strongly reduced hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial ß-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. CONCLUSIONS: Malnutrition leads to severe impairments in hepatic peroxisomal and mitochondrial function, and hepatic metabolic dysfunction. We discuss the potential future implications of our findings for the clinical management of malnourished children. LAY SUMMARY: Severe malnutrition in children is associated with metabolic disturbances that are poorly understood. In order to study this further, we developed a malnutrition animal model and found that severe malnutrition leads to an impaired function of liver mitochondria which are essential for energy production and a loss of peroxisomes, which are important for normal liver metabolic function.


Assuntos
Desnutrição , Trifosfato de Adenosina , Animais , Criança , Fígado Gorduroso , Humanos , Fígado , Mitocôndrias , Oxirredução , Ratos
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