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

Abstract

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

Diets intervene osteoporosis via gut-bone axis

“…Previous studies have suggested that both the quality and quantity of dietary fat intake might influence the composition and abundance of gut microbiota. 74 The unsaturated fatty acids change the composition and abundance of gut microbiota by enhancing ratio of Bacteroidetes to Firmicutes 75 . N -3 polyunsaturated fatty acids ( N -3 PUFA) can result in beneficial alterations in gut microbiota, including the addition of Bifidobacterium , Lactobacillus , Streptococcus , Vibrio desulphuricum , and Akkermania mucophilus .…”

Effects of Habitual Dietary Change on the Gut Microbiota and Health of Silkworms

“…For instance, metabolic dysfunction induced by an HFD is associated with alterations in gut microbial composition and metabolic products [19,33]. Berberine has been shown to effectively alleviate gut dysbiosis in mice fed an HFD; to increase the abundance of beneficial microorganisms such as Akkermansia and Parabacteroides; and to directly inhibit HFD-associated colorectal cancer through gut microbiota-regulated lyso-phosphatidylcholine [34]. A spirulina platensis polysaccharides intervention has been found to alter the relative abundance of intestinal microorganisms and decrease cecal levels of propionic acid in HFD-fed rats, thereby attenuating lipid and carbohydrate metabolism disorders induced by the HFD [22,35].…”

The Links between Food Components, Dietary Habits and Gut Microbiota Composition

“…Berberine intake has been shown to alleviate gut barrier disruption and inhibit colon inflammation in high-fat-diet-fed mice. Meanwhile, berberine can ameliorate gut microbial dysbiosis and can induce increases in beneficial gut microbiota, including Akkermansia and Parabacteroides [7].…”