A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes.

Mus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we report the development of a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and the derivation of a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. In this work, we show that the GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers opportunities for research focused on how the microbiota shapes host physiology in health and disease.

Agomelatine restores a physiological response to stress in the aged rat.

Short duration immobilization stress (IS) in younger rats is followed by a sleep rebound involving slow wave sleep (SWS) and, more particularly, rapid eye movement (REM) sleep. This rebound, expressing the ability of the brain to confront a stress challenge, is now accepted as a marker of the homeostasis. In older rats (24-25 months), however, an IS of 1h is not followed by a sleep rebound. To determine whether this impairment is reversible, we analyzed the effects of the antidepressant agomelatine, on stress-related sleep rebound in older animals. Older and younger (3-5 months) rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and polygraphic recordings were achieved under basal conditions with a digitized set-up. Older rats were pretreated with agomelatine (40mg/kg/day) for 3 days, with IS applied on the third day, whereas younger rats were only subjected to IS. Polygraphic recordings achieved under basal conditions confirmed the conventional impairments of the sleep/wake architecture in older animals, including decreased delta power, shortened REM sleep bouts, and modified sleep/wake circadian rhythms. Older rats pretreated with agomelatine for 3 days showed a reversal of the deficit observed in the beta-1, but not in the delta, EEG power band. Application of an IS to older rats after agomelatine pretreatment resulted in a REM sleep rebound in response to stress. These findings indicate that agomelatine, by improving beta-1 EEG power band and by inducing stress-related sleep rebound in older animals, contributes to the homeostasis maintenance.