Berberine, a potential prebiotic to indirectly promote Akkermansia growth through stimulating gut mucin secretion

• Published in: Biomedicine & pharmacotherapy Vol. 139; p. 111595
• Main Authors: Dong, Chaoran, Yu, Jiaqi, Yang, Yanan, Zhang, Fang, Su, Wenquan, Fan, Qinhua, Wu, Chongming, Wu, Shengxian
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-07-2021; Elsevier
• Subjects: Akkermansia - drug effects; Akkermansia - growth & development; Akkermansia muciniphila; Animals; Berberine; Berberine - pharmacology; Colon - drug effects; Colon - metabolism; Diet, High-Fat; Feces - chemistry; Feces - microbiology; Gastrointestinal Microbiome - genetics; Jagged-1 Protein - genetics; Male; Metabolomics; Mice; Mice, Inbred ICR; Mucin secretion; Mucins - metabolism; Polyamine; Polyamines - metabolism; Prebiotics; Receptor, Notch1 - genetics; RNA, Ribosomal, 16S; Transcription Factor HES-1 - genetics; Berberine; Polyamine; BBR; HFD; GC-TOF/MS; Mucin secretion; DFMO; Akkermansia muciniphila
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111595

Akkermansia spp. plays important roles in maintenance of host health. Increasing evidence reveals that berberine (BBR) may exert its pharmacological effects via, at least partially, promotion of Akkermansia spp. However, how BBR stimulates Akkermansia remains largely unknown.
In this study, we investigated the mechanism underlying the Akkermansia-promoting effect of BBR.
The effect of BBR on Akkermansia was assessed in BBR-gavaged mice and direct incubation. The influence of BBR on intestinal mucin production was determined by alcian-blue staining and real-time PCR. The feces were analysis by gas chromatography–time-of-flight mass spectrometry (GC-TOF/MS) metabolomics. The role of polyamines in BBR-elicited mucin secretion and Akkermansia growth was evaluated by administration of difluoromethylornithine (DFMO) in mice.
Gavage of BBR dose-dependently and time-dependently increased the abundance of Akkermansia in mice. However, it did not stimulate Akkermansia growth in direct incubation, suggesting that BBR may promote Akkermansia in a host-dependent way. Oral administration of BBR significantly increased the transcription of mucin-producing genes and mucin secretion in colon. Untargeted metabolomics analysis showed that BBR increased polyamines production in feces which are known to stimulate goblet cell proliferation and differentiation, but treatment with eukaryotic polyamine synthase inhibitor DFMO did not abolish the stimulating effect of BBR on mucin secretion and Akkermansia growth, indicating that the gut bacteria-derived but not the host-derived polyamines may involve in the BBR-promoted Akkermansia growth.
Our results reveal that BBR is a promising prebiotic for Akkermansia, and it promotes Akkermansia growth via stimulating mucin secretion in colon.
[Display omitted]
•Berberine is a potent prebiotic for Akkermansia.•Berberine promotes Akkermansia growth via stimulating mucin secretion in host intestine.•The research puts forward a novel insight into the modulation of functional gut microbes.