Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

Abstract

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

“…These changes appear to be due to the action of the potential prebiotic berberine. It has been reported that berberine can alter the structure of the intestinal microbiota and reduce the a diversity (40), which is consistent with the results of the present study. In the combined Chinese and Western drugs group, FT3 and FT4 were negatively correlated with Faecalibacterium prausnitzii, TSH was positively correlated with Faecalibacterium prausnitzii, and Lactococcus lactis showed a strong negative correlation with FT4, indicating a close relationship between thyroid indicators and the microbiota.…”

Berberine Suppresses Lung Metastasis of Cancer via Inhibiting Endothelial Transforming Growth Factor Beta Receptor 1

“…Second, gut microbiome is an important target of BBR. Recently, we have demonstrated that BBR ameliorates ovariectomy-induced anxiety-like behaviors and visceral hypersensitivity by regulating the gut microbiome ( Fang et al, 2021 ; Zhang et al, 2021 ). In the current study, we cannot fully exclude the possibility that the gut microbiome might be involved in BBR preventing PC lung metastasis However, we propose that the direct modulation of BBR on TC-EC interaction might play a major role in the anti-metastatic effect of BBR.…”

The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes

“…The use of berberine in diabetic rats resulted in an increase in the number of Bacteroidetes and Lactobacillaceae, and a decrease in the number of Proteobacteria and Verrucomicrobia [134]. In contrast, in rats subjected to chronic stress, berberine increased the abundance of Verrucomicrobia, Bacteroides, Lachnoclostridium, Akkermansia, and Anaerostipes, and decreased the ratio of Firmicutes to Bacteroidetes by reducing the relative amount of Firmicutes [135]. By stimulating the growth of SCFA-producing bacteria, berberine prevents obesity and insulin resistance through the TLR4 signaling pathway [136,137].…”