Caloric restriction promotes functional changes involving short-chain fatty acid biosynthesis in the rat gut microbiota

Abstract

Caloric restriction (CR) is known to promote health and longevity, likely via modification of the gut microbiota (GM). However, functional and metabolic changes induced in the GM during CR are still unidentified. 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. Furthermore, these CR-induced effects were maintained up to adulthood and started to be reversed after a short-term diet change. We also found that CR alters the abundance of an array of host proteins released in stool, mainly related to epithelial barrier integrity and inflammation. Hence, our results provide thorough information about CR-induced modifications to GM and host functional activity, and might constitute the basis for novel GM-based approaches aimed at monitoring the effectiveness of dietary interventions.

Causal roles of mitochondrial dynamics in longevity and healthy aging

“…This suppression of methionine content is key to metformin‐induced longevity in C. elegans . On similar lines, several studies have shown that DR and exercise in different species significantly alter the host microbiome . It might be possible then that in addition to metformin, several other pro‐longevity interventions might exert their effect through microbial modulation of host mitochondrial dynamics and metabolism.…”

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

“…Likely, the beneficial effects of CR rely on multiple, highly connected intraand inter-cellular pathways. These include the modulation of genomic stability [43], counteraction of age-related epigenetic alterations [44], promotion of autophagy and of the optimal balance between protein synthesis and degradation [45], maintenance of the stem cells niche [46], regulation of tissue microenvironment [47] and of gut microbiota [48], amongst others.…”

Potential correlation between carbohydrate‐active enzyme family 48 expressed by gut microbiota and the expression of intestinal epithelial AMP‐activated protein kinase β

“…The KRONA chart displaying the bacterial taxonomic groups at the phylum level organized by relative abundance suggested that compared to the red meat diet-fed animals, the fiber diet-supplemented groups (HF group denoted by blue nested sectors domain) showed a significantly increase in the proportion of Bacteroidetes (denoted by blue taxonomy nodes; Figure 2a), which could be attributed to the fact that Bacteroidetes are the main degraders of DF (Kaoutari, Armougom, Gordon, Raoult, & Henrissat, 2013;Schroeder & Bäckhed, 2016). In contrast, a high proportion of the phylum Firmicutes was observed in the gut microbiota of the RM group, which has been suggested to assist the host in efficient harvesting of calories compared with the Bacteroidetes group (Ash, 2007;Tanca et al, 2018). (Figure 2a).…”

“…mented groups (HF group denoted by blue nested sectors domain)showed a significantly increase in the proportion of Bacteroidetes (denoted by blue taxonomy nodes;Figure 2a), which could be attributed to the fact that Bacteroidetes are the main degraders of DF(Kaoutari, Armougom, Gordon, Raoult, & Henrissat, 2013;Schroeder & Bäckhed, 2016). In contrast, a high proportion of the phylum Firmicutes was observed in the gut microbiota of the RM group, which has been suggested to assist the host in efficient harvesting of calories compared with the Bacteroidetes group(Ash, 2007;Tanca et al, 2018).For example, RM-fed mice displayed a relatively high abundance of Chlamydiaceae, Lachnospiraceae, and Erysipelotrichaceae at the family level, when compared with other experimental groups (Chen et al, 2017; Radomski, Franzke, Matthiesen, Karger, & Knittler, 2019). Additionally, members of the Lachnospiraceae and Erysipelotrichaceae families have previously been suggested to be associated with microbe TMA generation and development of atherosclerosis (Qiu, Tao, Xiong, Yu, & Wei, 2018).…”