The long-term high-fat and high-fructose diet (HFFD) exacerbates cognitive decline and gut microbiota disorder. Coreopsis tinctoria flower (CTF), grown at high altitudes, has been revered as a popular health-enhancing tea modulating glycolipid metabolism in Chinese. However, the neuroprotective effects of CTF against HFFD-induced cognitive decline remain to be elucidated. The present study investigated the hypothesis that the neuroprotective benefits of CTF are mediated by tryptophan metabolism derived from gut microbiota. The phytochemical characterization of CTF was performed by LC-MS/MS-assisted feature-based molecular networking method. Behavioral, neurophysiological and metabolic evaluations demonstrated CTF improved glycolipid metabolic disorders and cognitive decline in HFFD-fed mice. Integrative 16S rRNA sequencing and metabolomics analysis revealed CTF modulated the abundance of specific gut microbial genera (e.g., Colidextribacter) and enhanced gut bacteria-dependent tryptophan metabolites (especially indole-3-lactic acid and indole-3-carboxylic acid) levels in the hippocampus. Notably, antibiotic-induced depletion of microbiota abolished these metabolite changes and the neuroprotective effects of CTF, confirming the crucial role of the intestinal microbiota. Additionally, the protective effects of ICA and ILA on D-glucose induced synaptic damage in SH-SY5Y cells have been identified directly. These findings highlight the importance of microbiota-regulated tryptophan metabolism as a key mechanism behind the cognitive benefits of CTF, demonstrating its potential for managing metabolic disorder–related neurodegenerative conditions.
Sun et al. (Wed,) studied this question.
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