The gut microbiome is known to change in harmful ways with advancing age. In old people there are too many inflammatory microbes, versus too few microbes generating beneficial metabolites. Researchers here note that the practice of calorie restriction, well established to slow aging and extend life in numerous species, prevents much of this age-related shift in microbial populations in mice. Calorie restriction changes near every measure of metabolism and outcome of aging, which makes it challenging to determine which aspects of the response to calorie restriction are more or less important than one another. Determining the specific contribution of the gut microbiome to degenerative aging remains a work in progress.
The first and the most studied manipulation shown to increase lifespan in mammals is caloric restriction (CR). Numerous laboratories have shown that reducing food consumption by 30% to 50% (without malnutrition) consistently increases both the mean and maximum lifespans of both laboratory rats and mice. The effect of CR on longevity is not limited to rodents as CR has been shown to increase the lifespan of a large number of diverse animal models ranging from invertebrates (yeast, C. elegans, and Drosophila) to dogs and non-human primates.
Because the gastrointestinal (GI) system is the first organ/tissue that encounters the impact of reduced food consumption, there have been several studies on the effect of CR on the GI-system. With the advent of metagenomics, it is now possible to interrogate the colon microbiome and study the effect of CR. Two groups have reported that long-term CR had a significant impact on the microbiome of old mice. These studies were conducted with aging colonies of mice specific to those particular laboratories and for which there were no lifespan data. Because the institutional animal husbandry environment and the health status of the host can have a major impact on the microbiome, we felt it was important to establish the effect of CR on the microbiome of well characterized mice from the aging colony maintained by National Institute on Aging (NIA).
Life-long CR increased microbial diversity and the Bacteroidetes/Firmicutes ratio and prevented the age-related changes in the microbiota, shifting it to a younger microbial and fecal metabolite profile in both C57BL/6JN and B6D2F1 mice. Old mice fed CR were enriched in the Rikenellaceae, S24-7, and Bacteroides families. The changes in the microbiome that occur with age and CR were initiated in the cecum and further modified in the colon. Short-term CR in adult mice had a minor effect on the microbiome but a major effect on the transcriptome of the colon mucosa. These data suggest that CR has a major impact on the physiological status of the gastrointestinal system, maintaining it in a more youthful state, which in turn could result in a more diverse and youthful microbiome.