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1.
Sci Rep ; 11(1): 23230, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853343

RESUMO

Managing postprandial glycemic response, or the increase in blood sugar following a meal, is a crucial component to maintaining healthy blood sugar in patients with diabetes. To test whether oral probiotics can impact postprandial glycemic response, E. coli Nissle 1917 (EcN) was evaluated in an oral glucose tolerance test. Oral gavage of EcN concurrent with a glucose bolus reduced the post-gavage glycemic response in mice. However, there was no difference in glycemic response when comparing EcN to a mutant deficient in glucose metabolism. This suggests that while EcN can alter glycemic response to a glucose bolus, this effect is not mediated by direct uptake of glucose. Of the possible indirect effects EcN could have, gastric emptying rate was highlighted as a likely cause, but EcN had no effect on gastric emptying rate in mice. This leaves many more possible indirect explanations for the interaction between EcN and host glucose metabolism to be explored in future work.


Assuntos
Escherichia coli/metabolismo , Glucose/metabolismo , Probióticos/administração & dosagem , Animais , Escherichia coli/genética , Esvaziamento Gástrico , Teste de Tolerância a Glucose , Masculino , Camundongos Endogâmicos C57BL , Mutação
2.
Nat Med ; 25(7): 1104-1109, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235964

RESUMO

The human gut microbiome is linked to many states of human health and disease1. The metabolic repertoire of the gut microbiome is vast, but the health implications of these bacterial pathways are poorly understood. In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase in Veillonella relative abundance in marathon runners postmarathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill run time. Veillonella utilize lactate as their sole carbon source, which prompted us to perform a shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance postexercise. Using 13C3-labeled lactate in mice, we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill run time performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves run time via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance.


Assuntos
Atletas , Microbioma Gastrointestinal , Ácido Láctico/metabolismo , Metagenômica , Corrida , Veillonella/metabolismo , Animais , Exercício Físico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Propionatos/metabolismo
3.
Mol Microbiol ; 75(2): 426-39, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19943898

RESUMO

The ability of some microbial species to oxidize monomethylamine via glutamate-mediated pathways was proposed in the 1960s; however, genetic determinants of the pathways have never been described. In the present study we describe a gene cluster essential for operation of the N-methylglutamate pathway in the methylotrophic beta-proteobacterium Methyloversatilis universalis FAM5. Four major polypeptides from protein fractions displaying high activities of N-methylglutamate synthetase, N-methylglutamate dehydrogenase and gamma-glutamylmethylamide synthetase were selected for mass spectrometry-based identification. The activities of enzymes were associated with the presence of peptides identified as ferredoxin-dependent glutamate synthase (GltB2), large subunit of putative heterotetrameric sarcosine oxidase (SoxA) and glutamine synthetase type III (GSIII) respectively. A gene cluster (8.3 kb) harbouring gltB2, soxA and gsIII-like genes was amplified from M. universalis FAM5, sequenced and assembled. Two partial and six complete open reading frames arranged in the order soxBDAG-gsIII-gltB132 were identified and subjected to mutational analysis, functional and metabolic profiling. We demonstrated that gltB-like and sox-like genes play a key role in methylamine utilization and encode N-methylglutamate synthetase and N-methylglutamate dehydrogenase respectively. Metabolic, enzymatic and mutational analyses showed that the gsIII-like gene encodes gamma-glutamylmethylamide synthetase; however, this enzyme is not essential for oxidation of methylamine.


Assuntos
Betaproteobacteria/genética , Ácido Glutâmico/metabolismo , Metilaminas/metabolismo , Alanina/metabolismo , Proteínas de Bactérias/genética , Betaproteobacteria/efeitos dos fármacos , Betaproteobacteria/crescimento & desenvolvimento , Betaproteobacteria/metabolismo , Análise Mutacional de DNA/métodos , Perfilação da Expressão Gênica/métodos , Glutamato Sintase/genética , Glutamato Sintase/metabolismo , Ácido Glutâmico/genética , Ácido Glutâmico/farmacologia , Glutamina/metabolismo , Cinética , Família Multigênica , Fases de Leitura Aberta , Oxirredução , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo
4.
Neuropsychopharmacology ; 31(6): 1241-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16123746

RESUMO

Previous studies have demonstrated that repeated forced-swim stress-induced behaviors (including analgesia, immobility, and increased drug reward) were mediated by the release of endogenous prodynorphin-derived opioid peptides and subsequent activation of the kappa opioid receptor (KOR). We tested the generality of these effects using a different type of stressful situation: repeated social defeat. C57Bl/6 mice subjected to social defeat stress (SDS) over 3 days showed a characteristic stress-induced immobility and defeated-postural response, as well as stress-induced analgesia (SIA). Daily pretreatment with the KOR antagonist nor-binaltorphimine (nor-BNI, 10 mg/kg, i.p.) blocked the SIA and significantly reduced the stress-induced immobility on the second and third days of SDS exposure. In contrast, prodynorphin gene-disrupted mice showed no significant increase in immobility, socially defeated postures, or SIA following repeated exposure to SDS. Since both stress and the kappa opioid system can modulate the response to drugs of abuse, we tested the effects of SDS on cocaine-conditioned place preference (CPP). SDS-exposed mice conditioned with cocaine (15 mg/kg, s.c.) showed significant potentiation of place-preference for the drug-paired chamber over the responses of unstressed mice. Nor-BNI pretreatment blocked stress-induced potentiation of cocaine-CPP. Consistent with this result, mice lacking the prodynorphin gene did not show stress-induced potentiation of cocaine-CPP, whereas wild-type littermates did. The findings suggest that chronic SDS may activate the kappa opioid system to produce analgesia, immobility, social defeat postures, and resulting in a potentiation of the acute rewarding properties of cocaine.


Assuntos
Comportamento Animal/fisiologia , Encefalinas/genética , Precursores de Proteínas/genética , Receptores Opioides kappa/fisiologia , Comportamento Social , Estresse Psicológico/fisiopatologia , Análise de Variância , Anestésicos Locais/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Encefalinas/deficiência , Resposta de Imobilidade Tônica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/métodos , Precursores de Proteínas/deficiência , Tempo de Reação/genética
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