Tryptophan　metabolism　has　shown　to　involve　in　pathogenesis　of　various　metabolic　diseases.　Gut　microbiota-orientated　diets　hold　great　potentials　to　improve　metabolic　health　via　regulating　tryptophan　metabolism.　The　present　study　showed　that　the　6-week　high　fat　diet　(HFD)　disturbed　tryptophan　metabolism　accompanied　with　gut　dysbacteriosis,　also　influenced　the　dietary　tryptophan　induced　changes　in　cecum　microbiome　and　serum　metabolome　in　mice.　The　colonic　expressions　of　aryl　hydrocarbon　receptor　(AhR)　and　interleukin-22　(IL-22)　were　significantly　reduced　in　mice　fed　on　HFD.　Notably,　a　diet-　rich　in　wheat　bran　effectively　inhibited　transformation　of　tryptophan　to　kynurenine-pathway　metabolites,　while　increased　melatonin　and　microbial　catabolites,　i.e.　indole-3-propionic　acid,　indole-3-acetaldehyde　and　5-hydroxy-indole-3-acetic　acid.　Such　regulatory　effects　were　accompanied　with　reduced　fasting　glucose　and　total　triglycerides,　and　promoted　AhR　and　IL-22　levels　in　HFD　mice.　Wheat　bran　increased　the　abundance　of　health　promoting　bacteria　(e.g.,　Akkermansia　and　Lactobacillus),　which　were　significantly　correlated　with　tryptophan　derived　indolic　metabolites.　Additionally,　beneficial　modulatory　effects　of　wheat　bran　on　indolic　metabolites　in　associations　with　gut　dysbacteriosis　from　type　2　diabetes　patients　were　confirmed　in　vitro　fecal　fermentation　experiment.　Our　study　proves　the　detrimental　effects　of　HFD　induced　gut　dysbacteriosis　on　tryptophan　metabolism　that　may　influence　immune　modulation,　and　provides　novel　insights　in　the　mechanisms　by　which　wheat　bran　could　induce　health　benefits.　©　2022　Elsevier　Ltd