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2.
Nutrients ; 14(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35745195

RESUMO

BACKGROUND: Long-term impact of different forms of severe acute malnutrition (SAM) in childhood on the emergence of noncommunicable diseases (NCDs) is poorly known. AIM: To explore the association between subtypes of SAM during childhood, NCDs, and cardiovascular risk factors (CVRFs) in young adults 11 to 30 years after post-SAM nutritional rehabilitation. METHODS: In this follow-up study, we investigated 524 adults (mean age 22 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007. Among them, 142 had a history of marasmus, 175 of kwashiorkor, and 207 had mixed-form SAM. These participants were compared to 407 aged- and sex-matched control adults living in the same community without a history of SAM. Our outcomes of interest were cardiometabolic risk markers for NCDs. Logistic and linear regressions models were sued to estimate the association between subtype of SAM in childhood and risk of NCDs. RESULTS: Compared to unexposed, former mixed-type SAM participants had a higher adjusted ORs of metabolic syndrome [2.68 (1.18; 8.07)], central obesity [1.89 (1.11; 3.21)] and low HDL-C (High-density lipoprotein cholesterol) [1.52 (1.08; 2.62)]. However, there was no difference between groups in terms of diabetes, high blood pressure, elevated LDL-C (low-density lipoprotein cholesterol) and hyper TG (hypertriglyceridemia) and overweightness. Former mixed-type SAM participants had higher mean fasting glucose [3.38 mg/dL (0.92; 7.7)], reduced muscle strength [-3.47 kg (-5.82; -1.11)] and smaller hip circumference [-2.27 cm (-4.24; -0.31)] compared to non-exposed. Regardless of subtypes, SAM-exposed participants had higher HbA1c than unexposed (p < 0.001). Those with a history of kwashiorkor had cardiometabolic and nutritional parameters almost superimposable to those of unexposed. CONCLUSION: The association between childhood SAM, prevalence of NCDs and their CVRFs in adulthood varies according to SAM subtypes, those with mixed form being most at risk. Multicenter studies on larger cohorts of older participants are needed to elucidate the impact of SAM subtypes on NCDs risk.


Assuntos
Hipertensão , Kwashiorkor , Desnutrição Proteico-Calórica , Desnutrição Aguda Grave , Adulto , Idoso , Colesterol , Doença Crônica , República Democrática do Congo/epidemiologia , Seguimentos , Humanos , Hipertensão/complicações , Kwashiorkor/epidemiologia , Desnutrição Proteico-Calórica/complicações , Desnutrição Aguda Grave/epidemiologia , Desnutrição Aguda Grave/terapia , Adulto Jovem
3.
Front Immunol ; 13: 826268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585989

RESUMO

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children's health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus-a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.


Assuntos
Kwashiorkor , Desnutrição , Desnutrição Proteico-Calórica , Rotavirus , Animais , Criança , Vida Livre de Germes , Humanos , Kwashiorkor/complicações , Kwashiorkor/metabolismo , Camundongos , Desnutrição Proteico-Calórica/complicações , Desnutrição Proteico-Calórica/metabolismo , Suínos
5.
Lancet Glob Health ; 10(5): e673-e684, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35427524

RESUMO

BACKGROUND: Mortality among children with acute illness in low-income and middle-income settings remains unacceptably high and the importance of post-discharge mortality is increasingly recognised. We aimed to explore the epidemiology of deaths among young children with acute illness across sub-Saharan Africa and south Asia to inform the development of interventions and improved guidelines. METHODS: In this prospective cohort study, we enrolled children aged 2-23 months with acute illness, stratified by nutritional status defined by anthropometry (ie, no wasting, moderate wasting, or severe wasting or kwashiorkor), who were admitted to one of nine hospitals in six countries across sub-Saharan Africa and south Asia between Nov 20, 2016, and Jan 31, 2019. We assisted sites to comply with national guidelines. Co-primary outcomes were mortality within 30 days of hospital admission and post-discharge mortality within 180 days of hospital discharge. A priori exposure domains, including demographic, clinical, and anthropometric characteristics at hospital admission and discharge, as well as child, caregiver, and household-level characteristics, were examined in regression and survival structural equation models. FINDINGS: Of 3101 children (median age 11 months [IQR 7-16]), 1120 (36·1%) had no wasting, 763 (24·6%) had moderate wasting, and 1218 (39·3%) had severe wasting or kwashiorkor. Of 350 (11·3%) deaths overall, 234 (66·9%) occurred within 30 days of hospital admission and 168 (48·0%) within 180 days of hospital discharge. 90 (53·6%) post-discharge deaths occurred at home. The proportion of children who died following discharge was relatively preserved across nutritional strata. Numerically large high-risk and low-risk groups could be disaggregated for early mortality and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical, and nutritional domains acting indirectly through anthropometric status. INTERPRETATION: Among diverse sites in Africa and south Asia, almost half of mortality occurs following hospital discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a child-centred, risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality, and clinical trials of these approaches with outcomes of mortality, readmission, and cost are warranted. FUNDING: The Bill & Melinda Gates Foundation.


Assuntos
Mortalidade da Criança , Kwashiorkor , Doença Aguda , África ao Sul do Saara/epidemiologia , Assistência ao Convalescente , Ásia/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Alta do Paciente , Estudos Prospectivos
6.
J Dev Orig Health Dis ; 13(6): 750-756, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35229708

RESUMO

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.


Assuntos
Resistência à Insulina , Kwashiorkor , Desnutrição Proteico-Calórica , Desnutrição Aguda Grave , Adulto , Criança , Humanos , Lactente , Kwashiorkor/complicações , Desnutrição Proteico-Calórica/complicações , Insulina , Adiponectina , Desnutrição Aguda Grave/complicações , Transtornos do Crescimento , Glucose
7.
EBioMedicine ; 75: 103791, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35030356

RESUMO

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.


Assuntos
Kwashiorkor , Desnutrição , Desnutrição Proteico-Calórica , Carbono , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Kwashiorkor/etiologia , Kwashiorkor/metabolismo , Desnutrição Proteico-Calórica/metabolismo
8.
Am J Clin Nutr ; 114(3): 925-933, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33963736

RESUMO

BACKGROUND: Kwashiorkor is an often-fatal type of severe acute malnutrition affecting hundreds of thousands of children annually, but whose etiology is still unknown. Evidence suggests inadequate sulfur amino acid (SAA) status may explain many signs of the condition but studies evaluating dietary protein intake in relation to the genesis of kwashiorkor have been conflicting. We know of no studies of kwashiorkor that have measured dietary SAAs. OBJECTIVES: We aimed to determine whether children in a population previously determined to have high prevalence of kwashiorkor [high-prevalence population (HPP)] have lower dietary intakes of SAAs than children in a low-prevalence population (LPP). METHODS: A cross-sectional census survey design of 358 children compared 2 previously identified adjacent populations of children 36-59 mo old in North Kivu Province of the Democratic Republic of the Congo. Data collected included urinary thiocyanate (SCN), cyanogens in cassava-based food products, recent history of illness, and a 24-h quantitative diet recall for the child. RESULTS: The HPP and LPP had kwashiorkor prevalence of 4.5% and 1.7%, respectively. A total of 170 children from 141 households in the LPP and 169 children from 138 households in the HPP completed the study. A higher proportion of HPP children had measurable urinary SCN (44.8% compared with 29.4%, P < 0.01). LPP children were less likely to have been ill recently (26.8% compared with 13.6%, P < 0.01). Median [IQR] intake of SAAs was 32.4 [22.9-49.3] mg/kg for the LPP and 29.6 [18.1-44.3] mg/kg for the HPP (P < 0.05). Methionine was the first limiting amino acid in both populations, with the highest risk of inadequate intake found among HPP children (35.1% compared with 23.6%, P < 0.05). CONCLUSIONS: Children in a population with a higher prevalence of kwashiorkor have lower dietary intake of SAAs than children in a population with a lower prevalence. Trial interventions to reduce incidence of kwashiorkor should consider increasing SAA intake, paying particular attention to methionine.


Assuntos
Aminoácidos Sulfúricos/administração & dosagem , Transtornos da Nutrição Infantil/etiologia , Dieta , Proteínas na Dieta/química , Comportamento Alimentar , Kwashiorkor/etiologia , Estado Nutricional , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/prevenção & controle , Transtornos da Nutrição Infantil/urina , Pré-Escolar , Estudos Transversais , República Democrática do Congo/epidemiologia , Inquéritos sobre Dietas , Humanos , Kwashiorkor/epidemiologia , Kwashiorkor/prevenção & controle , Manihot/química , Metionina/administração & dosagem , Fatores de Risco , Desnutrição Aguda Grave
9.
Am J Case Rep ; 22: e928468, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33536404

RESUMO

BACKGROUND Kwashiorkor disease is a subtype of severe acute protein malnutrition characterized by peripheral edema associated with hypoalbuminemia and ascites. It can result from both protein deficiency and protein loss. In resource-poor countries, the disease often is caused by inadequate dietary intake, but in resource-rich countries, it can be seen as a rare complication of severe malabsorption. CASE REPORT We present the case of a 60-year-old woman who presented with 1 week of progressive anasarca in the setting of decreased dietary intake and poor tolerance of total parenteral nutrition (TPN). She had a history of Roux-en-Y gastric bypass surgery which was complicated by a strangulated internal hernia that required an exploratory laparotomy and small bowel resection. She subsequently developed short gut syndrome with TPN dependence. Work-up revealed hypoalbuminemia with several micronutrient deficiencies consistent with secondary kwashiorkor disease. With a multidisciplinary approach that included Gastroenterology, Pharmacy, and Nutrition, she was treated with albumin, furosemide, nutritional supplementation, and ultimately rechallenged with TPN. At discharge, her swelling had improved, her weight had decreased, and her albumin improved to the normal range. CONCLUSIONS This case is a unique presentation of secondary kwashiorkor disease. In our patient, the combination of gastric bypass surgery and short gut syndrome with poor TPN tolerance likely led to severe protein malabsorption. This underscores the importance of recognizing the signs and symptoms of kwashiorkor disease and understanding the associated complications so that treatment can be instituted promptly. Furthermore, the case demonstrates how an interdisciplinary approach to management can increase the chance of a successful outcome.


Assuntos
Derivação Gástrica , Microbioma Gastrointestinal , Kwashiorkor , Síndrome do Intestino Curto , Edema , Feminino , Derivação Gástrica/efeitos adversos , Humanos , Kwashiorkor/etiologia , Pessoa de Meia-Idade , Síndrome do Intestino Curto/complicações
15.
Microb Pathog ; 150: 104702, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33359074

RESUMO

Kwashiorkor and marasmus are two clinical syndromes observed in severe acute malnutrition. In this review, we highlighted the differences between these two syndromes by reviewing the data comparing kwashiorkor and marasmus in literature, combined with recent microbiological findings and meta-analysis. Depletion of antioxidants, vitamins and minerals were more severe in kwashiorkor than marasmus. This was consistent with the severe and uncontrolled oxidative stress associated with the depletion of gut anaerobes and the relative proliferation of aerotolerant gut pathogens. This relative proliferation and invasion of gut microbes belonging to the aerotolerant Proteobacteria phylum and pathogens suggested a specific microbial process critical in the pathogenesis of kwashiorkor. Liver mitochondrial and peroxisomal dysfunction could be secondary to toxic microbial compounds produced in the gut such as ethanol, lipopolysaccharides and endotoxins produced by Proteobacteria, particularly Klebsiella pneumoniae, and aflatoxin produced by Aspergillus species. The gut-liver axis alteration is characterized by oedema and a fatty and enlarged liver and was associated with a dramatic depletion of methionine and glutathione, an excessive level of free circulating iron and frequent lethal bacteraemia by enteric pathogens. This was consistent with the fact that antibiotics improved survival only in children with kwashiorkor but not marasmus. The specific pathogenic characteristics of kwashiorkor identified in this review open new avenues to develop more targeted and effective treatments for both marasmus and/or kwashiorkor. Urgent correction of plasma glutathione depletion, alongside supply of specific essential amino acids, particularly methionine and cysteine, early detection of pathogens and an antibiotic more efficient than amoxicillin in supressing gut Proteobacteria including K. pneumoniae, and probiotics to restore the human gut anaerobic mature microbiota could save many more children with kwashiorkor.


Assuntos
Microbioma Gastrointestinal , Kwashiorkor , Desnutrição Proteico-Calórica , Desnutrição Aguda Grave , Amoxicilina , Criança , Humanos , Lactente , Kwashiorkor/terapia
16.
Toxicon ; 185: 174-183, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693007

RESUMO

Originally, the kwashiorkor is a pathology justified by the low consumption of proteins and high carbohydrates in weaned children. However, today, it can appear due to multifactorial causes, one of the hypotheses being the presence of aflatoxins in foods consumed by the child population and detected in biological fluids. The objective of this work is to scoping review the presence of aflatoxins in kwashiorkor, marasmus and marasmic-kwashiorkor from organs and biological samples in children. Results reflected that the presence of aflatoxins in kwashiorkor is greater compared to marasmic-kwashiorkor and marasmus in the organs and biological samples analyzed. The relationship of this mycotoxin with the pathology shows that it can affect both genders, even up to 12 years, in addition they are detected in eight biological samples and organs, except in the spleen, and in ten African countries and in the Philippines. The appearance of this pathology has been associated in children when after weaning they consume foods with low protein content and rich in carbohydrates, but coincidentally coincides with foods where the growth of aflatoxigenic fungi is more prevalent, and even the presence of other fungi that can generate other mycotoxins, such as ochratoxin A and fumonisin B1.


Assuntos
Aflatoxinas/metabolismo , Kwashiorkor/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Criança , Pré-Escolar , Feminino , Fumonisinas/metabolismo , Humanos , Lactente , Masculino , Micotoxinas/metabolismo , Ocratoxinas/metabolismo
17.
World Neurosurg ; 142: e331-e336, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32652272

RESUMO

OBJECTIVE: To identify if there are cultural, medical, educational, economic, nutritional and geographic barriers to the prevention and treatment of spina bifida and hydrocephalus. METHODS: The mothers of infants with spina bifida and hydrocephalus admitted to Muhimbilli Orthopaedic Institute, Dar Es Salaam, Tanzania, between 2013 and 2014 were asked to complete a questionnaire. A total of 299 infants were identified: 65 with myelomeningoceles, 19 with encephaloceles, and 215 with isolated hydrocephalus. The questionnaire was completed by 294 of the mothers. RESULTS: There was a high variation in the geographic origin of the mothers. Approximately 85% traveled from outside of Dar Es Salaam. The mean age was 29 (15-45) years old with a parity of 3 (1-10). The rates of consanguinity, obesity, antiepileptic medication, HIV seropositivity, and family history were 2%, 13%, 0%, 2%, and 2%, respectively. A maize-based diet was found in 84%, and only 3% of woman took folic acid supplementation, despite 61% of mothers stating that they wished to conceive another baby. Unemployment was high (77%), a low level of education was common (76% not attended any school or obtaining a primary level only), and 20% were single mothers. Hospital only was the preferred method of treatment for 94% of the mothers, and 85% of the babies were born in a hospital. CONCLUSIONS: Our study highlights some of the cultural, educational, geographic, nutritional, and economic difficulties in the prevention and management of spina bifida and hydrocephalus in Tanzania.


Assuntos
Encefalocele/prevenção & controle , Ácido Fólico/uso terapêutico , Hidrocefalia/prevenção & controle , Meningomielocele/prevenção & controle , Mães , Disrafismo Espinal/prevenção & controle , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Entorno do Parto/estatística & dados numéricos , Consanguinidade , Dieta/estatística & dados numéricos , Suplementos Nutricionais , Escolaridade , Encefalocele/epidemiologia , Encefalocele/cirurgia , Feminino , Geografia , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde , Hospitais , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/cirurgia , Kwashiorkor/epidemiologia , Meningomielocele/epidemiologia , Meningomielocele/cirurgia , Pessoa de Meia-Idade , Obesidade Materna/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Desnutrição Proteico-Calórica/epidemiologia , Pesquisa Qualitativa , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/cirurgia , Inquéritos e Questionários , Tanzânia/epidemiologia , Desemprego/estatística & dados numéricos , Adulto Jovem , Zea mays
18.
Cardiol Young ; 29(10): 1278-1281, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31475645

RESUMO

We report a case of a 13-year-old male with trisomy 21 in Southwestern Ontario, Canada, who presented with bilateral pneumonia, pericardial effusion, and peripheral oedema. The pericardial effusion did not respond to standard treatment options. Evaluation revealed severe dietary restriction, consistent with kwashiorkor. Hospital course was complicated by severe hypoalbuminaemia, hypocalcaemia, hypomagnesaemia, and hypophosphataemia. The pericardial effusion and other findings resolved gradually upon slow introduction of a well-balanced diet and adequate caloric and protein intake. Kwashiorkor is an unusual cause of pericardial effusion and can be overlooked especially in developed countries. It is a type of protein-calorie malnutrition often seen in children of impoverished countries and famine. It is a result of insufficient protein intake in the context of adequate caloric intake. Pericardial effusion not responding to usual treatment is a challenge, and other aetiologies must be considered. Malnutrition is often underdiagnosed or misdiagnosed in developed countries with devastating outcomes if unrecognised. This makes it imperative to consider this diagnosis, recognise potential risk factors, and be prepared to accurately assess overall nutritional status.


Assuntos
Ecocardiografia/métodos , Kwashiorkor/complicações , Derrame Pericárdico/diagnóstico , Pericárdio/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Humanos , Kwashiorkor/diagnóstico , Masculino , Derrame Pericárdico/etiologia
19.
Dev Cell ; 51(1): 7-20.e6, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31474562

RESUMO

The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.


Assuntos
Proteínas na Dieta/metabolismo , Enterócitos/metabolismo , Absorção Intestinal , Intestinos/embriologia , Lisossomos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Íleo/embriologia , Íleo/metabolismo , Kwashiorkor/metabolismo , Ligantes , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Receptores de Superfície Celular/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
20.
Sci Rep ; 9(1): 9084, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235833

RESUMO

Kwashiorkor and marasmus are considered to be two different clinical diseases resulting from severe malnutrition, but this distinction has been questioned. In a previous study comparing children with kwashiorkor and healthy children from Niger and Senegal, we found a dramatic gut microbiota alteration with a predominant depletion of anaerobes and enrichment in Proteobacteria and Fusobacteria in kwashiorkor. However, it remained unknown whether this association was related to malnutrition or was a specific feature of kwashiorkor. In this continuation study, we added 7 new marasmus subjects and 71,162 new colonies from the same countries. Our results showed that, compared to marasmus, the kwashiorkor gut microbiota was characterized by an increased proportion of Proteobacteria (culturomics, Marasmus 5.0%, Kwashiorkor 16.7%, p < 0.0001; metagenomics, Marasmus 14.7%, Kwashiorkor 22.0%, p = 0.001), but there was a decreased proportion of Bacteroidetes in marasmus (culturomics, Marasmus 0.8%, Kwashiorkor 6.5%, p = 0.001; metagenomics, Marasmus 5.4%, Kwashiorkor 7.0%, p = 0.03). Fusobacterium was more frequently cultured from kwashiorkor. All detected potential pathogenic species were enriched in the kwashiorkor gut microbiota. These results provide a biological basis to support the usage of an antibiotic therapy more effective in suppressing the overgrowth of bacterial communities resistant to penicillin, combined with antioxidants and probiotics for nutritional recovery therapies, particularly for kwashiorkor.


Assuntos
Bacteroidetes/isolamento & purificação , Fusobactérias/isolamento & purificação , Microbioma Gastrointestinal , Kwashiorkor/microbiologia , Desnutrição Proteico-Calórica/microbiologia , Proteobactérias/isolamento & purificação , Biodiversidade , Estudos de Casos e Controles , Feminino , Humanos , Masculino
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