Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism

Wang, Yan; Shou, Jia‐Wen; Li, Xiaoyang; Zhao, Ziran; Fu, Jie; He, Chi‐Yu; Ren, Feng; Ma, Chao; Wen, Bao‐Ying; Guo, Fang; Yang, Xinyi; Han, Yan‐Xing; Wang, Lulu; Tong, Qian; You, Xuefu; Lin, Yuan; Kong, Weijia; Si, Shuyi; Jiang, Jian‐Dong

doi:10.1016/j.metabol.2017.02.003

Cited by 159 publications

(118 citation statements)

References 59 publications

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“…26 As the leading action site of berberine is the gut, the impact of berberine on regulating intestinal microbiota composition greatly contributes to its pharmacological effects. 27 In this study, we found that berberine regulated alcohol-induced dysbiosis. Berberine significantly decreased richness and diversity of the gut flora and changed the overall composition of flora community.…”

Section: Discussionmentioning

confidence: 55%

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Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

Wang

Tan

et al. 2020

Clinical & Translational Med

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Background Berberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear. Aim To investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota‐immune system axis. Method An animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing. Results We first reported the promising beneficial effect of berberine on ameliorating acute‐on‐chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota‐immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic‐ myeloid‐derived suppressor cell (G‐MDSC)‐like population, in the liver of mice with alleviating alcohol‐induced hepatic injury. Berberine remarkably enhanced the increase of G‐MDSC‐like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G‐MDSC‐like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G‐MSDCs‐like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G‐MDSC‐like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population. Conclusion Collectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.

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Section: Discussionmentioning

confidence: 55%

“…[23][24][25] Modulating intestinal microbiota composition via pharmacological agents might be the promising direction for treatment of ALD. 26 As berberine is treated as a potent regulator on intestinal flora, [27][28][29] the role of intestinal bacteria changes in regulating G-MDSC-like cells was also examined.…”

Section: Introductionmentioning

confidence: 99%

Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

Wang

Tan

et al. 2020

Clinical & Translational Med

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“…SCFAs may contribute to the BBR activity in the regulation of GLP-1 in vivo. BBR was reported to regulate the lipid metabolism through an impact on SCFAs 30 . In L-cells, SCFAs induce GLP-1 expression and secretion by stimulation of GPR43, which are supported by the effects of dietary fibers 31 , 32 .…”

Section: Discussionmentioning

confidence: 99%

Restoration of GLP-1 secretion by Berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice

et al. 2018

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ObjectiveL-cell dysfunction is reported for GLP-1 reduction in type 2 diabetes. However, the mechanism of dysfunction remains unknown. In this study, we examined mitochondrial function in the mechanistic study in diet-induced obese (DIO) mice.SubjectsC57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks to establish the DIO model for GLP-1 reduction. The mice were then treated with berberine (BBR) (100 mg/kg/day) for 8 weeks to test the impact on GLP-1 expression. Mitochondrial activities of the colon enterocytes were compared among three groups of mice (lean, DIO, and DIO + BBR) at the end of treatment. Gut microbiota and short-chain fatty acids (SCFAs) were examined to understand the mitochondrial responses. A cellular model treated with palmitic acid (PA) was used in the mechanism study.ResultsA reduction in GLP-1 expression was observed in DIO mice with mitochondrial stress responses in the colon enterocytes. The mitochondria exhibited cristae loss, membrane rupture, and mitochondrial swelling, which was observed with an increase in ATP abundance, complex I activity, and deficiency in the activities of complexes II and IV. Those changes were associated with dysbiosis and a reduction in SCFAs in the colon of DIO mice. In the cellular model, an increase in ATP abundance, loss of mitochondrial potential, and elevation of apoptosis were induced by PA. All of the alterations in DIO mice and the cellular model were attenuated by BBR.ConclusionThe mitochondrial stress responses were observed in the colon enterocytes of DIO mice for GLP-1 reduction. The stress was prevented by BBR in the restoration of GLP-1 expression, in which BBR may act through direct and indirect mechanisms.

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“…Next, we picked representative sequences for each OTU (operational taxonomic units) and used the RDP (ribosomal database project) classifier to annotate taxonomic information for each representative sequence. Sequences with a similarity over 97% were assigned to the same OTUs 22.…”

Section: Methodsmentioning

confidence: 99%

Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

et al. 2017

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Nitroreductases (NRs) are bacterial enzymes that reduce nitro-containing compounds. We have previously reported that NR of intestinal bacteria is a key factor promoting berberine (BBR) intestinal absorption. We show here that feeding hamsters with high fat diet (HFD) caused an increase in blood lipids and NR activity in the intestine. The elevation of fecal NR by HFD was due to the increase in either the fraction of NR-producing bacteria or their activity in the intestine. When given orally, BBR bioavailability in the HFD-fed hamsters was higher than that in those fed with normal chow (by +72%, *P<0.05). BBR (100 mg/kg/day, orally) decreased blood lipids in the HFD-fed hamsters (**P<0.01) but not in those fed with normal diet. Clinical studies indicated that patients with hyperlipidemia had higher fecal NR activity than that in the healthy individuals (**P<0.01). Similarly, after oral administration, the blood level of BBR in hyperlipidemic patients was higher than that in healthy individuals (*P<0.05). Correlation analysis revealed a positive relationship between blood BBR and fecal NR activity (r=0.703). Thus, the fecal NR activity might serve as a biomarker in the personalized treatment of hyperlipidemia using BBR.

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Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism

Cited by 159 publications

References 59 publications

Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

Restoration of GLP-1 secretion by Berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice

Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

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