Multi-omic analysis reveals the anti-aging impact of sulforaphane on the microbiome and metabolome

Abstract

Background Dietary factors may modulate many complex interactions between the microbiome, metabolome, and immune system and can have an impact on the functional status of older adults. Sulforaphane (SFN), a natural compound and Nrf2-related activator of cytoprotective genes, provides a wide range of biological effects from cancer prevention to reducing insulin resistance. We have shown that SFN increased survival and improved cardiac and skeletal muscle function in a mouse model of aging. This study aims to investigate the anti-aging effects of SFN on the gut microbiome and metabolome.Results Young (6-8 weeks of age) and old (21-22 months of age) male C57BL/6J mice were provided regular rodent chow or chow containing SFN for 2 months. Fecal samples were collected right before and at the completion of SFN administration. We profiled the gut microbiome and applied global metabolomic profiling to fecal samples. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the microbiome, and metabolome. Microbial diversity, composition and functional capacity varied substantially across different age groups. On a global level, in old mice we observed that the SFN diet restored the gut microbiome to mimic that in young mice. In old mice, the SFN diet enriched bacteria associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. In addition, the tricarboxylic acid cycle, central in cellular respiration, was decreased and amino acid metabolism-related pathways were increased. SFN diet induced metabolite biomarkers in old mice that are associated majorly with the genera, Oscillospira , Ruminococcus , and Allobaculum.Conclusion In old mice, SFN directed the metabolic potential to that of young animals. Integrated microbiome and metabolome analyses revealed metabolite biomarkers that could be modulated by bacteria and contribute to the anti-aging effects of SFN. Collectively, our results provide evidence in support of a novel hypothesis that SFN diet exerts anti-aging effects by influencing the gut microbiome and metabolome. Although further investigations are needed to identify precise mechanisms, modulating the gut microbiome by SFN may have the potential to promote healthier aging.