Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
PLoS Negl Trop Dis ; 14(10): e0008737, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33006970

RESUMO

Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa are disproportionately affected by non-typhoidal S. enterica bloodstream infections. To inform a clinical trial in people, we investigated vitamin A as a treatment in the context of antibiotic treatment failure in a mouse model of vitamin A deficiency. Vitamin A-deficient (VAD) mice exhibited higher systemic bacterial levels with a multidrug-resistant clinical isolate in comparison to mice on a control diet. Sex-specific differences in vitamin A deficiency and disseminated infection with S. enterica serotype Typhimurium (S. Typhimurium) were observed. VAD male mice had decreased weight gain compared to control male mice. Further, infected VAD male mice had significant weight loss and decreased survival during the course of infection. These differences were not apparent in female mice. In a model of disseminated S. Typhimurium infection and antibiotic treatment failure, we assessed the potential of two consecutive doses of vitamin A in alleviating infection in male and female mice on a VAD or control diet. We found that subtherapeutic antibiotic treatment synergized with vitamin A treatment in infected VAD male mice, significantly decreasing systemic bacterial levels, mitigating weight loss and improving survival. These results suggest that assessing vitamin A as a therapy during bacteremia in malnourished patients may lead to improved health outcomes in a subset of patients, especially in the context of antibiotic treatment failure.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Salmonella/tratamento farmacológico , Salmonella typhimurium/efeitos dos fármacos , Vitamina A/administração & dosagem , Animais , Bacteriemia/microbiologia , Suplementos Nutricionais , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Feminino , Masculino , Desnutrição/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Salmonella/microbiologia , Fatores Sexuais , Taxa de Sobrevida , Deficiência de Vitamina A/fisiopatologia
2.
Cell Host Microbe ; 28(2): 273-284.e6, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32668218

RESUMO

The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.


Assuntos
Antibacterianos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Disbiose/patologia , Metabolismo Energético/fisiologia , Doenças Inflamatórias Intestinais/microbiologia , Síndrome do Intestino Irritável/microbiologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Disbiose/induzido quimicamente , Enterobacteriaceae/crescimento & desenvolvimento , Microbioma Gastrointestinal , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/metabolismo , Mesalamina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , PPAR gama/agonistas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA