How can disrupting circadian rhythms contribute to inflammatory disease?
Circadian rhythms enforce a 24-hour cycle on our bodies and are often mentioned in conjunction with jet lag. Now, researchers have found that when these rhythms are disrupted and combined with a high-fat, high-sugar diet, they could contribute to inflammatory bowel disease and other conditions.
The researchers, from Rush University Medical Center in Chicago, IL, publish their results in the journal PLOS ONE.
First author of the study Prof. Robin M. Voigt explains that circadian rhythms are not sleep patterns, but rather: "Sleep is a consequence of circadian rhythms."
In our modern lives, there are many people whose circadian rhythms are disrupted on a regular basis. Shift workers, for example - including nurses, doctors, firefighters and policemen - have regularly disrupted patterns.
"Other people have 'social jet lag,' a lifestyle pattern that leads them to maintain a normal schedule on weekdays, but then stay up late and sleep in on the weekends," says Voigt.
But these shifts in rhythms do more than make us groggy, suggests the team, adding that these disruptions may advance other diseases that could be prevented by regulating sleep/wake patterns and eating times.
Voigt says this issue needs to be addressed:
"If you have some of these other risk factors, like a high-fat, high-sugar diet, take precautions, watch your diet, take pre- and probiotics, monitor your health, be vigilant."
The researchers note that adding prebiotics or probiotics to the diet can help to normalize circadian rhythm disruption effects on the intestinal microbiota, which could reduce inflammation.
Mice with disrupted rhythms and unhealthy diets fared the worst
Inflammation in the body is linked with diseases like cardiovascular disease, cancer, inflammatory bowel disease and neurological disorders. The team says such diseases have been found to coincide with disruption of normal microbiota communities or circadian rhythms.
Interestingly, research has shown that the number of microbial cells in the gastrointestinal tract outnumber total human cells in the body. Voigt and her team explain that the discovery of circadian clock genes in mammals has aided our understanding of how most cells in the body contain the "molecular machinery necessary to generate circadian rhythms."
The mice whose circadian rhythms were disrupted and who were fed a high-sugar, high-fat diet had higher concentrations of bacteria that promote inflammation.
The researchers worked on the basis of a "second hit hypothesis," which asserts that individuals with at-risk lifestyles or genetic factors will only develop a disease if a second threat is present.
"We believe that chronic circadian rhythm disruption promotes/exacerbates inflammatory-mediated diseases," says Voigt, "at least in part, due to changes in the intestinal microbiota."
To conduct their study, the team reversed cycles of exposure to light and dark on a weekly basis for male mice, which is known to disrupt innate circadian rhythms.
While some of the mice ate standard food, others were fed a high-fat, high-sugar diet. There was also a control group of mice whose circadian rhythms were not disrupted.
The microbiota of the mice whose rhythms were disrupted were significantly different from the control group, but only if they were fed the high-fat, high-sugar diet. Additionally, all mice that ate the unhealthy diet showed changes in the microorganism makeup in their guts, regardless of circadian shifts.
Mice that ate the high-fat, high-sugar diet and whose circadian rhythms were disrupted had higher concentrations of bacteria that promote inflammation, compared with any of the other mice in the study, the researchers say.
However, the mice who were fed a standard diet and whose rhythms were disrupted did not have significantly altered intestinal microbiota.
Despite limitations, findings are significant
The authors say their findings show the negative effects of circadian disruptions are such that "a second environmental insult is often necessary to reveal [their] deleterious effects."
Though their findings are significant, the authors do point to certain limitations of their study. Firstly, it did not include an age-matched chow-fed control group of mice, so it is difficult to determine which changes could have occurred as a result of age.
Additionally, because such a control group was absent, the team says the impact of the liquid diet or the content is difficult to assess.
The team says future studies evaluating microbial community function should try to determine effects of circadian rhythm changes in microbiome function - including short chain fatty acid production, metabolites linked to stress, obesity, insulin resistance and inflammation.
"Despite these limitations," write the researchers, "we have, for the first time, determined that circadian disorganization impacts the intestinal microbiome in high-fat, high-sugar fed mice."
Written by Marie Ellis
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