Gut Microbiota Modulates Behavior in Adult Mice: Potential Role for Microbial‐ Metabolite Sensors in the Brain
Notice bibliographique
Résumé
The gut microbiota plays a defined role in the physiology of the gastrointestinal (GI) tract, digesting foods, metabolizing essential vitamins, and protecting the host against opportunistic pathogens. Composed of a complex community of microorganisms, the microbiota is reasonably stable in the adult individual. Due to the extensive bidirectional communication of the GI tract and the central nervous system, it has been demonstrated that the gut microbiota is capable of modulating brain function. However, the contributions of the microbiota to psychological behaviors in the adult are incompletely understood. Moreover, mechanism(s) by which this modulation occurs have also still to be completely elucidated. We hypothesize that gut microbiota influence brain activity and host behavior, signaling via bacterial metabolites acting at distinct receptors in the brain. Metabolites generated by the microbiota are found in the bloodstream and they are altered in accordance with microbial changes, such as in antibiotic treatment. Therefore, antibiotic treatment represents an attractive means for us to test our hypothesis. We assessed the expression of potential microbial‐metabolite sensors in the brain of C57Bl/6 male mice. A broad‐spectrum antibiotic cocktail was administered to mice for 2 weeks to deplete the bacterial community of the intestinal microbiota. The efficacy of antibiotic administration was verified through quantification of the bacterial load and composition in the cecal matter after treatment. Following treatment, behavior was assessed applying the elevated plus maze and the open field test for anxiety‐like behavior and locomotion; the 3‐chamber test for social preference; and the tail suspension test for depression‐like behavior. Microbial metabolite sensing receptors were analyzed in the brain by qPCR. Mice treated with antibiotics had reduced bacterial load and altered composition in the cecal matter, without changes in body weight. No changes were observed in anxiety‐like behavior, locomotion, and social preference when compared to controls. Interestingly, antibiotic‐treated mice presented with a reduction in depressive‐like behavior. Measurement of microbial‐metabolite sensors (e.g. aryl hydrocarbon receptor, AHR; pregnane X receptor; PXR) in the brain were performed to correlate their expression with the phenotypic behavior observed. mRNA of AHR was highly expressed in different regions of the brain ‐ hippocampus, amygdala, and hypothalamus, while levels of PXR mRNA were low in all regions. Moreover, antibiotic treatment reduced expression of AHR mRNA in hippocampus compared to control, whilst no alterations were observed in the amygdala and hypothalamus. These data suggest that changes in the intestinal microbiota lead to specific behavioral alterations. These changes may be driven, in part, by alterations in the expression and/or activity of microbial‐metabolite sensing receptors in the brain. Further work is required to determine if AHR activity directly modulates brain regions responsible for depression‐like behavior. Support or Funding Information Canadian Institutes of Health Research (CIHR) and National Counsel of Technological and Scientific Development (CNPq – Brazil) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».