Environmentally induced changes in the gut microbiome and their role in the metabolic syndrome

Abstract

Previous studies have shown that lifestyle affects the gut microbiome. For example, a diet low in fiber leads to progressive loss of gut microbiome diversity across generations in mice. Industrial populations have a higher prevalence of obesity and lower bacterial richness compared to non-industrial populations. Here, we explore environmentally induced changes in the gut microbiome and their relationship with the metabolic syndrome. First, we studied the ancestral gut microbiome from eight human palaeofaeces (1,000-2,000 years old). We performed a large-scale de novo assembly of microbial genomes from the palaeofaeces and reconstructed 498 medium- and high-quality genomes. The palaeofaeces are more similar to modern-day non-industrialized human gut microbiomes relative to modern-day industrialized human gut microbiomes. This study demonstrates that industrialization is correlated with changes in the human gut microbiome relative to its ancestral state. Next, to model human obesity in mice, we fed C57BL/6 mice with a high-fat diet over 4 generations and observed changes in the gut microbiome. The most obese mice did not yield progenies, whereas the leanest mice successfully reproduced and their offspring were also resistant to obesity. In other words, a population bottleneck was observed. Because the mice were nearly genetically identical inbred mice, the variation in body weight gain was likely independent of genetics. We show that microbial factors might contribute to heterogeneity in weight gain and provide an adaptive advantage to the host. Finally, we investigated the effects of cold exposure and β3-adrenergic receptor (β3-AR) activation on the gut microbiome. Cold exposure activates β3-ARs in the brown adipose tissue, which results in increased thermogenesis and is correlated with lower body mass. Yet, pharmacological activation of β3-ARs does not fully recapitulate the effects of cold exposure. Here, we report a comprehensive dataset of metagenomic, metabolomic, and lipidomic analyses from the gut and the circulation of mice exposed to either cold or β3-AR activation. Overall, we show changes in the gut microbiome induced by environmental factors and their contribution to the metabolic syndrome. Understanding the impact of lifestyle on the gut microbiome and its relationship with obesity is critical for preventing further deterioration of our gut microbiomes.