Prebiotics may mitigate health impacts of body-clock disruptions

Funded by the US Office of Naval Research, the study found that rats exposed to chronic disruption of rhythms (CDR) while eating prebiotics adjusted sleep and core body temperature diurnal rhythms to an altered light/dark cycle more quickly than those fed a control diet.

“These results support our overarching hypothesis that prebiotics can effectively mitigate the negative impacts of chronic disruption of circadian rhythms on physiology and sleep/wake behaviour,” ​wrote the researchers, in the journal 'Brain Behavior and Immunity'​.

Time to find solutions for CDR​

People who work night shifts or irregular hours commonly experience CDR due to altered light exposure, jet lag, disturbed or restricted sleep and eating at the wrong times of day. CDR not only impacts sleep but can also result in circadian misalignment of physiological systems, which is associated with increased disease risk. There is therefore a need to find ways of facilitating realignment and reducing the probability of physiological rhythm misalignment, with dietary intervention being one potential solution.

In previous studies, the same researchers found that galactooligosaccharide (GOS) and polydextrose (PDX) induce favourable changes in gut microbial ecology and promote a stress robust phenotype.

What they didn’t know, however, was whether these prebiotics can reduce the physiological strain of CDR or influence the realignment of physiological rhythms like sleep and core body temperature. Therefore, the team sought to investigate this through a study in which rats were fed diets enriched with GOS and PDX or a control diet for five weeks, then exposed to light-dark reversal for eight weeks to induce CDR.

Rats fed the prebiotic diet realigned their core body temperature and sleep/wake rhythms to the new light/dark cycle more quickly than those on the control diet. The prebiotic diet also produced an increased abundance of Ruminiclostridium 5​ and Parabacteroides distasonis​ - ​species that are associated with positive health status.

Several possible mechanisms​

Whilst the mechanisms for how prebiotic induced changes in gut microbial ecology impact brain functions and physiology are largely unknown, the researchers say it is feasible that dietary prebiotics change microbially mediated bile acid composition and bile acid signalling.

In this study, the prebiotic diet was found to modify faecal bile acid profiles. The prebiotic diet also reduced levels of several secondary and secondary conjugated bile acids and CDR significantly increased cholic/taurocholic acid in faeces. After light/dark reversal, rats with high levels of Ruminiclostridium 5​ and lower levels of taurocholic/cholic acid realigned CBT rhythms and sleep faster than rats with lower levels of these good bacteria and higher levels of cholic/taurocholic acid.

“It is feasible to suggest that the increased abundance of bacteria capable of biotransformation of bile acids may result in lower levels of fecal taurocholic acid and alter bile acid signalling to the brain,” ​wrote the researchers, acknowledging that additional work is needed to determine whether modulations in bile acid profiles contribute to the effects.

They also said it was possible that reason for the lower faecal secondary and secondary conjugated bile acid levels induced by the prebiotic diet could be explained by more efficient gut reabsorption.

They said their results are consistent with previous findings and suggest that increased faecal output of bile acids, like cholic acid, may be indicative of a chronic stress-like state within the gut microbial-bile acid environment that could contribute to negative health outcomes.

Overall, they concluded that consumption of prebiotics is an effective strategy to increase the abundance of health-promoting microbes, alter the faecal bile acid profile and facilitate the recovery and realignment of sleep and diurnal rhythms after circadian disruption.

Source: Brain Behavior and Immunity​

Thompson RS, Gaffney M, Hopkins S, Kelley T, Gonzalez A, Bowers SJ, Vitaterna MH, Turek FW, Foxx CL, Lowry CA, Vargas F, Dorrestein PC, Wright KP Jr, Knight R, Fleshner M.

"Ruminiclostridium 5​, Parabacteroides distasonis​, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms"

https://doi.org/10.1016/j.bbi.2021.07.006