Berberine alters gut microbial function through modulation of bile acids

Abstract

Background: Berberine (BBR) is a plant-based nutraceutical that has been used for millennia to treat diarrheal infections and in contemporary medicine to improve patient lipid profiles. Reduction in lipids, particularly cholesterol, is achieved partly through up-regulation of bile acid synthesis and excretion into the Gastrointestinal tract. The efficacy of BBR is also thought to be dependent on structural and functional alterations of the gut microbiome. However, knowledge of the effects of BBR on gut microbiome communities is currently lacking. Distinguishing indirect effects of BBR on bacteria through altered bile acid profiles is particularly important in understanding how dietary nutraceuticals alter the microbiome. Results: Germfree mice were colonized with a defined minimal gut bacterial consortium capable of functional bile acid metabolism (Bacteroides vulgatus, Bacteroides uniformis, Parabacteroides distasonis, Bilophila wadsworthia, Clostridium hylemonae, Clostridium hiranonis, Blautia producta; B4PC2). Multi-omics (bile acid metabolomics, 16S rDNA sequencing, cecal metatranscriptomics) were performed in order to provide a simple in vivo model from which to identify network-based correlations between bile acids and bacterial transcripts in the presence and absence of dietary BBR. Significant alterations in network topology and connectedness in function were observed, despite similarity in gut microbial relative abundance between control and BBR treatment. BBR increased cecal bile acid concentrations and altered the taurocholic acid:tauro-β-muricholic acid ratio in the liver. Overall, analysis of correlation networks indicates both bacterial species-specific responses to BBR, as well as functional commonalities among species, such as up-regulation of Na+/H+ antiporter, cell wall synthesis/repair, carbohydrate metabolism and amino acid metabolism. Bile acid concentrations in the gastrointestinal (GI) tract increased significantly during berberine treatment and developed extensive correlation networks with expressed genes in the B4PC2 community. Conclusions: This work has important implications for interpreting the effects of berberine on structure and function of the complex gut microbiome, which may lead to targeted pharmaceutical interventions aimed to achieve the positive physiological effects previously observed with berberine supplementation.

Microbiome and metabolome analyses reveal significant alterations of gut microbiota and bile acid metabolism in ETEC-challenged weaned piglets by dietary berberine supplementation

“…Besides, our results showed that BBR treatment upregulated CYP7A1 and CYP27A1 expression in the liver, and promotes liver primary bile acid biosynthesis. This indicated BBR might display its beneficial effect in alleviating intestinal inflammation by regulation of bile acid metabolism in piglets followed by ETEC challenge, which was in consistent with previous study that BBR exerted its therapeutic effect by promoting bile acid synthesis (Wolf et al, 2021).…”

Efficacy and underlying mechanisms of berberine against lipid metabolic diseases: a review

“…For example, DCA and LCA have a high affinity for TGR5, while CDCA and CA have a high affinity for FXR. Upon BBR treatment, increased CA and CDCA activate FXR (Wolf et al, 2021). FXR plays a central role in regulating BA synthesis.…”

“…Bile, as one of the pathways of BBR excretion, is also regulated by BBR-related signaling pathways. It has been found that BBR affects bile excretion by regulating the gut microbiota and acting on the farnesoid X receptor (FXR) -CYP7A1/ CYP8B1 pathway (Guo et al, 2016;Wolf et al, 2021). However, due to the hepatoenteric circulation of bile acids (BAs), the amount of BBR and its derivatives excreted through bile is small.…”