Extracts of Chrysanthemum morifolium Ramat. alleviated colitis-induced cognitive dysfunction through the BDNF/TrkB/CREB signaling pathway

Cognitive impairment is a frequent neurological comorbidity of inflammatory bowel disease (IBD). The neuroprotective mechanisms of Chrysanthemum morifolium (CM) and its flavonoid-rich extracts (FL) remain unclear. The aim of this study was to examine the protective effects of CM and FL on colitis and related cognitive impairment in mice, as well as to explore its potential mechanisms. This study analyzed the flavonoid composition of CM and FL using LC-MS. The results revealed that FL substantially enriches phenylpropanoids and flavonoids compared to crude CM. DSS-induced colitis model was utilized to evaluate CM, FL efficacy, followed by ABX-mediated microbiota depletion and FMT to determine the necessity and sufficiency of the gut microbiota in mediating these protective effects. Assessments included behavioral tests, barrier integrity, neuroinflammation (LPS/cytokines), 5-HT levels, 16S rRNA sequencing and gene expression detection. CM and FL significantly alleviated colonic inflammation and barrier damage. In the brain, interventions suppressed LPS-mediated TLR4/MyD88 signaling, restored 5-HT homeostasis, and activated the BDNF/TrkB/CREB axis, enhancing synaptic plasticity. Microbiota analysis showed enriched SCFA-producing bacteria and reduced pathobionts (Alistipes, Romboutsia). ABX treatment abolished FL neuroprotection, while FMT from FL-treated donors (F-FMT) successfully restored cognitive function and signaling pathways in recipient mice. This study confirms that Chrysanthemum morifolium extracts alleviate colitis-induced cognitive dysfunction by modulating the microbiota-gut-brain axis and activating the BDNF/TrkB/CREB signaling pathway. These findings support its development as a natural dietary intervention for treating the neurological complications associated with IBD.