A new approach of gut microbiota modulation by probiotic bacterial cells: formulation for use in metabolic endotoxemia
Notice bibliographique
Résumé
The human gut microbiota plays an important role in the maintenance of human health. It forms a tremendous and complex bacterial bioreactor located in the human intestinal tract. An imbalance of the gut microbiota ecosystem, a state called gut dysbiosis, can disrupt the microbiota's functions. Endotoxins are immunogenic molecules produced by the gut microbiota that cause metabolic endotoxemia, a disorder characterized by low levels of circulating endotoxins that contribute to the development of many human diseases, including type 2 diabetes mellitus, obesity, and liver, cardiovascular, and inflammatory bowel diseases. Although many strategies have been developed to combate high dose endotoxemia such as in sepsis, none is available for use in metabolic endotoxemia. Thus, there is an urgent need for the development of an effective strategy for use in metabolic endotoxemia. In this thesis, the potential of a novel probiotic bacterial cells formulation to modulate the gut microbiota and reduce circulating endotoxtins was investigated in a series of in vitro and in vivo experiments. An in vitro human colonic microbiota model, easy to set up and that ensures long-term ecosystem stability, was developed. Probiotic bacteria - identified from the literature for their anti-inflammatory effects - were screened for colonic endotoxins reduction using the model. It was shown that Lactobacillus and Bifidobacterium strains modulated specifically colonic endotoxins concentrations, with Bifidobacterium longum subsp. infantis ATCC 15697 showing the highest reduction. B. infantis ATCC 15697 was further encapsulated within alginate-poly-L-lysine-alginate (APA) microcapsules and characterized for the colon targeted delivery of viable cells in flask studies and in a well-established human multistage gastrointestinal (GI) model. Results showed that APA microencapsulation delivery system significantly increased the cell survival of B. infantis ATCC 15697 to simulated human GI transit conditions, as well as enhanced the gut microbiota enrichment of loaded probiotic cells in the colon, as compared to the unencapsulated probiotic strain. The potential of the novel probiotic formulation to modulate the gut microbiota for use in metabolic endotoxemia was further tested in the human multistage GI model and in F344 rats. Results showed that APA microencapsulated B. infantis ATCC 15697 reduced colonic endotoxins concentrations through the modulation of gut bacterial populations and metabolites in in vitro and in vivo experiments. Importantly, orally administered APA microencapsulated B. infantis ATCC 15697 lowered circulating endotoxins in F344 rats. Thus, this thesis work demonstrates the significant potential of APA microencapsulated B. infantis ATCC 15697 probiotic bacterial cells to modulate the gut microbiota and reduce circulating endotoxins for use in metabolic endotoxemia. Further studies are required to investigate the safety and potentials of the formulation in humans.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,002 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».