The aging mouse microbiome has obesogenic characteristics

Abstract

Background During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice. Methods Fecal and blood samples from adult (n = 42, 100–300 days) and aging (n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin. Results We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces. Conclusions We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.

Obesity Reshapes the Microbial Population Structure along the Gut-Liver-Lung Axis in Mice

“…Gut microbiota have been shown to regulate body fat content in mice [ 11 ] and are regarded as a putative target for obesity treatments [ 47 ]. As shown in the present study, HFD-driven obesity suppresses Bacteroidetes in the gut of mice ( Figure 3 C), an effect also observed in aging mice [ 49 ]. Moreover, HFD-driven obesity was found to increase the Firmicutes to Bacteroidetes ratio in the gut ( Figure 3 C), expanding on previous studies in genetically engineered obese mice and obese humans [ 50 , 51 ].…”

Host Immunity Influences the Composition of Murine Gut Microbiota

“…As the murine microbiota could be influenced by various factors inherent to animals or the environment, we first studied and showed that caecal microbial composition of the immunocompetent or immunocompromised mice groups in our study were not confounded by experimental variables such as housing cages, dates of experimental procedures, gender, or age. The effect of age, especially, has been strongly linked to an altered gut microbiota (32)(33)(34)(35)(36). This has been discussed and illustrated further in Supplementary Results, Supplementary Figure 2, and Supplementary Table 1.…”

“…A proportionately successive age category between 3-6 months, considered as adults (28), was chosen to mitigate any potential confounding effect of ageing in our immunodeficient mouse strains. This is because immunodeficiency causes differential ageing (29)(30)(31), and ageing is strongly linked to an altered gut microbiota profile (32)(33)(34)(35)(36). As no effect of ageing is known for NOD scid gamma mice (n = 26 mice; NSG, NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ, JAX) that is one of the most immunocompromised mouse strains known so far, we studied two age groups of 3-6 months (n = 19) and of 10 months (n = 7).…”

Dietary Supplementation throughout Life with Non-Digestible Oligosaccharides and/or n-3 Poly-Unsaturated Fatty Acids in Healthy Mice Modulates the Gut–Immune System–Brain Axis

“…A previous study has shown that enhanced intestinal abundance of Adlercreutzia is associated with inflammation-induced depressive-like behaviour in mice [ 105 ]. Increased expression of the genus Dehalobacterium in mice is associated with ageing and food intervention-induced anti-inflammatory effects [ 106 , 107 ]. Moreover, reduced levels of intestinal Dehalobacterium observed in BTBR mice that have an autistic phenotype are associated with enhanced marble burying [ 108 ].…”