Are antibiotic effects on sleep behavior in the rat due to modulation of gut bacteria?

The sleep-inducing substance Factor S (FS) is unique among candidate sleep molecules because of its bacterial origin. FS is derived from the bacterial cell wall and accumulates in the brain and body fluids of sleep-deprived animals including man. Exogenous administration of FS and related muramyl peptides results in an increase in slow-wave sleep (SWS). To test the possibility that gastrointestinal bacteria are a source of FS, rats were placed on an antibiotic regimen (neomycin and metronidazole in drinking water) and sleep measures taken after one week. There was a significant reduction in SWS in the first three hours of the lights-on period as well as an increase in sleep latency. No other sleep parameters, including Rapid Eye Movement (REM) sleep measures, were affected, suggesting that there was a specific SWS effect due to bacterial reduction. Possible toxic effects of the antibiotic treatment were unlikely factors in SWS reduction due to the stability of other sleep measures such as number of episodes of SWS and REM, total sleep time and REM latency. Oral administration of live E. coli to rats did not affect any sleep measures. It appears that FS may be specifically involved in the early sleep period where it promotes sleep onset and SWS generation.