Berberine inhibits high fat diet-associated colorectal cancer through modulation of the gut microbiota-mediated lysophosphatidylcholine

• DOI: 10.7150/ijbs.81824
• Publication Date: 2023-04-18T01:33:55Z
• Authors: Haitao Chen; Chenxiao Ye; Changhong Wu; Jiali Zhang; Lu Xu; Xuanying Wang; Chao Xu; Jin Zhang; Yong Guo; Qinghua Yao
• Keywords: Akkermansia muciniphila; Dysbiosis; Lysophosphatidylcholine; Akkermansia

Dietary fat intake is positively associated with elevated risk of colorectal cancer (CRC).Currently, clinical treatments remian inadequate bacause the complex pathogenesis CRC induced by a high-fat diet (HFD).Mechanistically, imbalances in gut microbiota are HFD-associated tumourigenesis.Therefore, we investigated anti-tumor activity berberine (BBR) modulating dysregulated and related metabolites preforming 16S rDNA sequencing liquid chromatography/mass spectrometry.As expected, BBR treatment significantly decreased number colonic polyps, ameliorated barrier disruption, inhibited colon inflammation oncogenic pathways AOM/DSS-induced model mice fed an HFD.Furthermore, alleviated dysbiosis increased abundance beneficial microorganisms, including Akkermansia Parabacteroides, HFD-fed mice.In addition, metabolomics analysis demonstrated altered glycerophospholipid metabolism during progression mice, whereas reverted these changes metabolites, particularly lysophosphatidylcholine (LPC), which was confirmed to promote cell proliferation ameliorate junction impairment.Notably, had no clear effects on depletion, transplantation BBR-treated microbiota-depleted recapitulated inhibitory tumourigenesis LPC levels.This study that directly through microbiota-regulated levels, thereby providing promising microbiota-modulating therapeutic strategy for prevention Western diet-associated CRC.