Members of the research community have in recent years exhibited a growing interest in the analysis of gut microbes in the context of metabolism and the pace of aging. Some inroads are being made into better understanding helpful versus unhelpful microbial populations and behaviors, and how exactly their activities might influence health over the long term. It is unclear as to how large this influence is. Perhaps it is in the same ballpark as exercise, but perhaps not. The usual problems arise when comparing results between species, in that short-lived species have greater plasticity of life span, their length of life more readily extended or shortened in response to changing circumstances. It should be no great surprise to find that the practice of calorie restriction, well known to slow aging in near all species tested to date, induces changes in gut microbial populations that conform to alterations that are seen as being helpful for health in other contexts.
The gut microbiota (GM) largely derives nutrients from dietary intake. In this respect, a large number of studies have been reported on the variations of the GM composition occurring according to different diets. The majority of these studies have focused on the comparison of low vs. high energy density (i.e., high fat or high sugar) diets in animals fed ad libitum (AL), showing an increase in the Firmicutes/Bacteroidetes ratio and the proliferation of pro-inflammatory Proteobacteria in the latter condition.These changes occur rapidly and can be partially restored by reverting to the control diet. Animal experimental data also agree with observational studies in humans, where similar taxonomic features were found to be changed between obese and lean individuals.
In addition, the GM composition varies rapidly and significantly in response to macronutrient changes, even when equal numbers of calories are provided. This clearly suggests that the relative abundance of the specific GM members strongly depends on the quality of nutrients they have access to. Hence, given the strong relationship among diet, GM and health, there is a growing interest in developing novel dietary strategies to modulate the composition and, possibly, the metabolic functions of the GM.
Among dietary interventions, caloric restriction (CR) is well known for the health-promoting impact on lipid metabolism and longevity. CR is generally applied without changing the macronutrient composition and solely reducing the caloric intake compared to the AL condition. As a consequence, in experimental models, caged individuals fed a CR diet consume completely their food and then fast for several hours before the next feed administration. We have recently reported that CR induces a rapid change (as early as after 3 weeks of CR) of the GM composition in young rats, that parallels a reduction of triglycerides and cholesterol levels in the blood, and that these changes are maintained up to mid age. In particular, a CR diet enabled the expansion of Lactobacillus rapidly and persistently up to adulthood. CR-induced variation of the GM composition might then play a role in helping extend lifespan and delay the onset of age-related disorders by preserving gut homeostasis. However, the precise biochemical changes the GM undergoes during CR are still undetermined, in the short and in the long term.
Here, we investigated the short- and long-term effects of CR on the rat GM using a metaproteogenomic approach. We show that a switch from ad libitum (AL) low fat diet to CR in young rats is able to induce rapid and deep changes in their GM metaproteomic profile, related to a reduction of the Firmicutes/Bacteroidetes ratio and an expansion of lactobacilli. Specifically, we observed a significant change in the expression of the microbial enzymes responsible for short-chain fatty acid biosynthesis, with CR boosting propionogenesis and limiting butyrogenesis and acetogenesis.