Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Abstract

Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.

Calorie Restriction Prevents Age-Related Changes in the Intestinal Microbiota

“…The Lactobacillus genus is the most common bacteria used in probiotics to protect against pathogen invasion and inflammatory bowel disorders (Martin et al, 2013). Our Lactobacillus data in B6D2F1 are similar to that previously reported for C57BL/6 mice by Zhang et al (2013) and Kok et al (2018) showing that life-long CR resulted in an increase in the Lactobacillus genus. The difference in microbial types observed between studies again emphasizes the influence of environment and strain have on the gut microbiome (Ericcson et al, 2018;Laukens et al, 2015).…”

“…The first study to show that life-long CR (30% started at 5 weeks of age) significantly changed the gut microbiota of old (15 and 35 months) mice was reported by Zhang et al (2013). Subsequently, Kok et al (2018) also reported that life-long CR (30% started at 9 weeks of age) significantly changed the microbiome of old (28 months) mice. However, in a study focusing primarily on response to influenza, Bartley et al (2017) reported that CR (40% starting at 3-4 months of age) had very little effect on the microbiome of old (19 to 21 months) mice.…”

“…These three studies used male C57BL/6 mice. The studies by Zhang et al (2013) and Kok et al (2018) were conducted on C57BL/6 obtained and maintained in either China or The Netherlands, respectively, while Bartley et al (2017) used C57BL/6JN mice obtained from the animal colony maintained by NIA. Because environment can have a major impact on the gut microbiome (Ericsson et al, 2018) and the NIA animal colony is maintained under optimal husbandry and used by investigators across the country, we believed it was important to characterize in detail the effect of CR on the microbiome in mice from the NIA animal colony microbiome.…”

“…With the advent of 16S rRNA sequencing and 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 (Zhang et al, 2013;Kok et al, 2018). These studies were conducted with aging colonies of mice specific to those particular laboratories and for which there were no lifespan data.…”

Effects of the intake of white wheat bread added with garlic and resistant starch: action on calcium bioavailability and metabolic parameters of growing Wistar rats

“…Several authors showed that caloric restriction may beneficially affect the indicators of colonic health in aging mice. 31 The reduction of food intake by the BGR group led to an increase of the L population and lower counts of the E population. Fig.…”