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1.
Sci Rep ; 13(1): 6114, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-37059733

RESUMO

Most lactobacilli produce extracellular polysaccharides that are considered to contribute to the probiotic effect of many strains. Lacticaseibacillus rhamnosus CNCM I-3690 is an anti-inflammatory strain able to counterbalance gut barrier dysfunction. In this study ten spontaneous variants of CNCM I-3690 with different EPS-production were generated and characterized by their ropy phenotype, the quantification of the secreted EPS and genetic analysis. Amongst them, two were further analysed in vitro and in vivo: an EPS over-producer (7292) and a low-producer derivative of 7292 (7358, with similar EPS levels than the wild type (WT) strain). Our results showed that 7292 does not have anti-inflammatory profile in vitro, and lost the capacity to adhere to the colonic epithelial cells as well as the protective effect on the permeability. Finally, 7292 lost the protective effects of the WT strain in a murine model of gut dysfunction. Notably, strain 7292 was unable to stimulate goblet cell mucus production and colonic IL-10 production, all key features for the beneficial effect of the WT strain. Furthermore, transcriptome analysis of colonic samples from 7292-treated mice showed a down-regulation of anti-inflammatory genes. Altogether, our results point out that the increase of EPS production in CNCM I-3690 impairs its protective effects and highlight the importance of the correct EPS synthesis for the beneficial effects of this strain.


Assuntos
Lacticaseibacillus rhamnosus , Probióticos , Animais , Camundongos , Lacticaseibacillus , Lactobacillus , Células Caliciformes , Anti-Inflamatórios , Polissacarídeos Bacterianos/farmacologia
2.
Biochim Biophys Acta ; 1852(5): 980-91, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25675848

RESUMO

The tryptophan/kynurenine pathway (TKP) is the main route of tryptophan degradation and generates several neuroactive and immunomodulatory metabolites. Experimental and clinical data have clearly established that besides fat, muscle and liver, pancreatic islet tissue itself is a site of inflammation during obesity and type 2 diabetes. Therefore it is conceivable that pancreatic islet exposure to increased levels of cytokines may induce upregulation of islet kynurenine metabolism in a way resembling that seen in the brain in many neurodegenerative disorders. Using normal rat islets and the INS-1 ß-cell line, we have demonstrated for the first time that: 1/only some TKP genes are constitutively expressed, both in ß-cells as well as non ß-cells; 2/ the regulatory enzyme indoleamine 2,3-dioxygenase (IDO1) is not constitutively expressed; 3/ IDO1 and kynurenine 3-monoxygenase (KMO) expression are potently activated by proinflammatory cytokines (IFN-γ, IL-1ß) and glucolipotoxicity respectively, rather in ß-cells than in non ß-cells; 4/ Islet kynurenine/kynurenic acid production ratio is enhanced following IFN-γ and glucolipotoxicity; 5/ acute exposure to KYN potentiates glucose-induced insulin secretion by normal islets; and 6/ oxidative stress or glucocorticoid modulates TKP genes only marginally. Pancreatic islets may represent a new target tissue for inflammation and glucolipotoxicity to activate the TKP. Since inflammation is now recognized as a crucial mechanism in the development of the metabolic syndrome and more specifically at the islet level, it is needed to evaluate the potential induction of the TKP in the endocrine pancreas during obesity and/or diabetes and its relationship to the islet cell functional alterations.


Assuntos
Citocinas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Cinurenina/metabolismo , Redes e Vias Metabólicas/genética , Animais , Western Blotting , Linhagem Celular Tumoral , Glucose/farmacologia , Peróxido de Hidrogênio/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Insulina/metabolismo , Secreção de Insulina , Interferon gama/farmacologia , Interleucina-1beta/farmacologia , Quinurenina 3-Mono-Oxigenase/genética , Quinurenina 3-Mono-Oxigenase/metabolismo , Masculino , Oxidantes/farmacologia , Palmitatos/farmacologia , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Triptofano/metabolismo
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