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Sulforaphane (SFN) exerts effects on aging, cancer prevention and reducing insulin resistance. This study investigated effects of SFN on the gut microbiome and metabolome in old mouse model compared with young mice. Young (6\u20138 weeks) and old (21\u201322 months) male C57BL\/6J mice were provided regular rodent chow \u00b1 SFN for 2 months. We collected fecal samples before and after SFN administration and profiled the microbiome and metabolome. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the gut microbiome, and metabolome. The SFN diet restored the gut microbiome in old mice to mimic that in young mice, enriching bacteria known to be associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. The tricarboxylic acid cycle decreased and amino acid metabolism-related pathways increased. Integration of multi-omic datasets revealed SFN diet-induced metabolite biomarkers in old mice associated principally with the genera, Oscillospira, Ruminococcus, and Allobaculum. Collectively, our results support a hypothesis that SFN diet exerts anti-aging effects in part by influencing the gut microbiome and metabolome. Modulating the gut microbiome by SFN may have the potential to promote healthier aging.<\/jats:p>","DOI":"10.3390\/microorganisms8101500","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T08:43:27Z","timestamp":1601369007000},"page":"1500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Multi-Omic Analysis Reveals Different Effects of Sulforaphane on the Microbiome and Metabolome in Old Compared to Young Mice"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-3950","authenticated-orcid":false,"given":"Se-Ran","family":"Jun","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}]},{"given":"Amrita","family":"Cheema","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Biochemistry, Molecular and Cellular Biology, University Medical Center, Washington, DC 20057, USA"}]},{"given":"Chhanda","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology &amp; Oncology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2249-5203","authenticated-orcid":false,"given":"Marjan","family":"Boerma","sequence":"additional","affiliation":[{"name":"Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}]},{"given":"Philip T.","family":"Palade","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}]},{"given":"Eugenia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-5717","authenticated-orcid":false,"given":"Sanjay","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology &amp; Oncology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-4558","authenticated-orcid":false,"given":"Sharda P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology &amp; Oncology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41392-019-0074-5","article-title":"Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome","volume":"4","author":"Zhang","year":"2019","journal-title":"Signal. 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