Unraveling the gut microbiome of the long-lived naked mole-rat

Abstract

The naked mole-rat (Heterocephalus glaber) is a subterranean mouse-sized African mammal that shows astonishingly few age-related degenerative changes and seems to not be affected by cancer. These features make this wild rodent an excellent model to study the biology of healthy aging and longevity. Here we characterize for the first time the intestinal microbial ecosystem of the naked mole-rat in comparison to humans and other mammals, highlighting peculiarities related to the specific living environment, such as the enrichment in bacteria able to utilize soil sulfate as a terminal electron acceptor to sustain an anaerobic oxidative metabolism. Interestingly, some compositional gut microbiota peculiarities were also shared with human gut microbial ecosystems of centenarians and Hadza hunter-gatherers, considered as models of a healthy gut microbiome and of a homeostatic and highly adaptive gut microbiota-host relationship, respectively. In addition, we found an enrichment of short-chain fatty acids and carbohydrate degradation products in naked mole-rat compared to human samples. These data confirm the importance of the gut microbial ecosystem as an adaptive partner for the mammalian biology and health, independently of the host phylogeny.

Figure 1

3D PCoA obtained by Bray-Curtis distance matrix showing the separation between naked mole-rats (pink), mice (green), western human adults (blue) and a group of different terrestrial mammalian species (carnivores in red (C1-C5), omnivores in orange (O1-O9), herbivores in yellow (H1-H17)) based on their gut microbial composition. Gut microbiota composition of terrestrial mammalian species was retrieved from Muegge et al., identification of these mammals is provided in the legend (left). Wild mouse gut microbiota was obtained from Weldon et al.. First, second and third principal component are showed, accounting for 25.8%, 22.9% and 8.1% of the total variance in the dataset.

Figure 2

Family level gut microbiota average profiles of naked mole-rats, wild mice, western human adults and supercentenarians and rural humans (Hadza). Families with average rel.ab > 0.8% are plotted. Color legends are reported for each profile to improve readability. Bacteroidetes and Firmicutes families are plotted in shades of blue and green, respectively.

Figure 3

Heat map analysis of fecal metabolites from human and naked mole-rat. Individual relative abundance of each metabolite from naked mole-rat and human samples. Each column represents one sample (N = naked mole-rat; H = human). Red color represents a higher relative abundance, while green color illustrates a lower relative abundance.

Figure 4

Polar metabolites in feces of the naked mole-rat. (a) Principal components analysis of GC-MS analysis of polar metabolites from the feces of naked mole-rat (NMR) and human samples (n = 5 each). The more distant the samples are in this graphic, the more their compound pattern differs. Naked mole-rat and human samples are separated on the level of principal component 1 which represents 58% of the variance; principle component 2 (10% variance) represents the variance within the replicates of one group. Clearly, naked mole-rat samples are far more distant to human samples than to each other. (b) Total ion current of GC-MS analyses of polar metabolites from the feces samples of naked mole-rat and human (n = 5 each). Top: Naked mole-rat replicates; Bottom: human sample replicates. Compound groups are labeled using brackets.