The mechanism of berberine alleviating metabolic disorder based on gut microbiome
Open accessAbstract
With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.
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Berberine can indirectly influence the disposition of other drugs by at least three routes: altering bacterial drug metabolism, modifying the enterohepatic circuit through regulation of bacterial β-glucuronidases, and modulating gut-barrier integrity.
“Therefore, berberine can indirectly influence the disposition of other drugs by at least three routes: altering bacterial drug metabolism, modifying the enterohepatic circuit through regulation of bacterial β-glucuronidases, and modulating gut-barrier integrity [95,104,105].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [95]
Section 4 says berberine alters gut microbiota and improves intestinal-barrier function; section 4.1 says gut microbiota can metabolize oral drugs. But the paper does not establish that berberine thereby changes the disposition of other drugs, and the passages found do not describe regulation of bacterial β-glucuronidases or an enterohepatic route for those drugs. No page numbers were available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBecause most of the berberine dose remains in the intestinal lumen, berberine remodels the composition of the microbiota and has broad-spectrum antimicrobial activity.
“Because most of the dose remains in the intestinal lumen, berberine remodels the composition of the microbiota and has broad-spectrum antimicrobial activity [95,96].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [95]
Section 4 says berberine changes the quantity, structure and composition of gut microbiota and can kill harmful intestinal bacteria. Section 4.1 reports oral bioavailability below 1%, consistent with limited absorption, but does not establish that most of the dose remains in the intestinal lumen. The passages do not establish broad-spectrum antimicrobial activity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBerberine enriches short-chain fatty-acid-producing bacteria, modulates bile-acid metabolism and remodels the microbiota in models of obesity and insulin resistance.
“Berberine enriches short-chain fatty-acid-producing bacteria, modulates bile-acid metabolism and remodels the microbiota in models of obesity and insulin resistance [95,97,98,99,100,101]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [95]
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“Consequently, the investigators try to find out solutions in order to solve the problem of poor bioavailability (Liu et al., 2010).”
BackgroundSREBPs in Lipid Metabolism, Insulin Signaling, and Beyond
DeBose‐Boyd, R. A., & Ye, J. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.01.005 · Cited by 356 · cited 1× · see citing works
“The regulation of adipose genetic expression by insulin and fatty acids is mainly mediated by transcriptional factor, for instance SREBPs (Debose-Boyd and Ye, 2018).”
BackgroundBerberine pharmacology and the gut microbiota: A hidden therapeutic link
Habtemariam, S. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104722 · Cited by 352 · cited 3× · see citing works
“%) as a result of poor aqueous solubility, the molecular structure of berberine Frontiers in Cellular and Infection Microbiology 04 prevents its rapid absorption from the intestine (Habtemariam, 2020).”
BackgroundInfluentialUnderstanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota
Xu, J., Chen, H., & Li, S. (2017) · Medicinal Research Reviews · doi:10.1002/med.21431 · Cited by 340 · cited 2× · see citing works
“Other studies have also shown (Xu et al., 2017) BBR significantly increased the levels of plasma GLP-1 and GLP-2 in portal vein, as well as the number of L-cells in proximal colon and the mRNA expression level of preluganin.”
BackgroundZou, K., Zhao, L., Zhang, Y., Zhang, H.-Y., Li, B., Zhu, W., Shi, J., Jia, Q., & Li, Y. (2016) · Acta Pharmacologica Sinica · doi:10.1038/aps.2016.125 · Cited by 317 · see citing works
Self-citationTransforming berberine into its intestine-absorbable form by the gut microbiota
Feng, R., Shou, J.-W., Zhao, Z.-X., He, C.-Y., Ma, C., Huang, M., Fu, J., Tan, X.-S., Li, X.-Y., Wen, B.-Y., et al. (2015) · Scientific Reports · doi:10.1038/srep12155 · Cited by 307 · see citing works
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300 · cited 1× · see citing works
“Recently, researchers have found that the disturbance of the gut-brain axis is closely related to the occurrence and development of metabolic diseases and exerts its effects through the hormone signaling pathway (Burokas et al., 2015).”
Background2-Oleoyl Glycerol Is a GPR119 Agonist and Signals GLP-1 Release in Humans
Hansen, K. B., ROSENKILDE, M. M., Knop, F. K., Wellner, N., Diep, T. A., Rehfeld, J. F., Andersen, U. B., Holst, J. J., & Hansen, H. S. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0647 · Cited by 298 · cited 1× · see citing works
“Studies indicated that Akkermansia muciniphila could significantly increase GLP-1 release from colonic L cells (Everard et al., 2011; Hansen et al., 2011), this study confirmed that BBR increased the abundance of akman bacteria and decreased the abundance of Lactobacillus, which seems to be related to the increase of…”
ResultThe structure and function of the glucagon‐like peptide‐1 receptor and its ligands
Donnelly, D. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01687.x · Cited by 292 · cited 1× · see citing works
“Studies have shown that GLP-1 promotes beta-cell neogenesis and satiety, reduces glucagon secretion, delays gastric emptying, and increases peripheral glucose disposal (Donnelly, 2012).”
BackgroundBerberine and Its Role in Chronic Disease
Cicero, A. F. G., & Baggioni, A. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-41334-1_2 · Cited by 285 · see citing works
Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans
Meijnikman, A. S., Gerdes, V. E. A., Nieuwdorp, M., & Herrema, H. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00192 · Cited by 280 · cited 1× · see citing works
“The relationship between the occurrence of metabolic disorders with the gut microbiota is one of the main research directions to explore the mechanism of metabolic disorders at present (Meijnikman et al., 2018).”
BackgroundTissue Distribution of Berberine and Its Metabolites after Oral Administration in Rats
Tan, X.-S., Ma, J.-Y., Feng, R., Ma, C., Chen, W.-J., Sun, Y.-P., Fu, J., Huang, M., He, C.-Y., Shou, J.-W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077969 · Cited by 266 · cited 1× · see citing works
“The extremely low plasma concentrations following oral administration of BBR in experimental or clinical settings are not sufficient to achieve the effects observed in in vitro experiments, which presents challenges in explaining its excellent and diverse pharmacological effects in clinical trials (Tan et al., 2013; L…”
BackgroundXiexin Tang improves the symptom of type 2 diabetic rats by modulation of the gut microbiota
Wei, X., Tao, J., Xiao, S., Jiang, S., Shang, E., Zhu, Z., Qian, D., & Duan, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-22094-2 · Cited by 255 · see citing works
(2002) · The Lancet · doi:10.1016/s0140-6736(02)07495-0 · Cited by 249 · cited 1× · see citing works
“Studies have confirmed that the absorption rate of DhBBR is 5-fold correspond to BBR in animals (Direct, 2002).”
Microbiome: Focus on Causation and Mechanism
Fischbach, M. A. (2018) · Cell · doi:10.1016/j.cell.2018.07.038 · Cited by 248 · cited 2× · see citing works
“…body metabolism leads to a causality still not fully clear and needs to be elucidated in more rational experimental designs and research approaches (Fischbach, 2018), it is hoped that gut frontiersin.org microbiome will become more widely used in clinical practice as a therapeutic target for…”
BackgroundXu, X., Yi, H., Wu, J., Kuang, T., Zhang, J., Li, Q., Du, H., Xu, T., Jiang, G., & Fan, G. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110984 · Cited by 246 · cited 7× · see citing works
“, 2017), metabolic (Xu et al., 2021), cardiovascular (Martini et al.”
BackgroundInfluentialPossemiers, S., Bolca, S., Verstraete, W., & Heyerick, A. (2010) · Fitoterapia · doi:10.1016/j.fitote.2010.07.012 · Cited by 238 · cited 1× · see citing works
“Some chemical components have been metabolized before the first-pass effect of liver, and the activity or toxicity of drugs can be significantly changed, affecting the exertion of drug efficacy (Sousa et al., 2008; Possemiers et al., 2011).”
BackgroundEfficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease
Yan, H., Xia, M., Wang, Y., Chang, X., Yao, X., Rao, S., Zeng, M., Tu, Y., Feng, R., Jia, W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134172 · Cited by 233 · see citing works
Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?
Sircana, A., Framarin, L., Leone, N., Berrutti, M., Castellino, F., Parente, R., Michieli, F. D., Paschetta, E., & Musso, G. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1057-6 · Cited by 223 · cited 1× · see citing works
“Both animal and human researches have shown that the increase of SCFAs concentration in feces is related to weight gain, fat accumulation and insulin resistance, which may be due to the increase of SCFAs production and the decrease of SCFAs absorption (Sircana et al., 2018).”
BackgroundMicrobiota and metabolites in metabolic diseases
Cani, P. D. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0143-9 · Cited by 221 · cited 1× · see citing works
“…(as F.prausnitzii (Xu et al., 2020a), A.muciniphila, R.intestinalis, Bifidobacterium and Akkermansia muciniphila.) in the gut (Everard et al., 2011; Qin et al., 2012; Tilg and Moschen, 2014; FIGURE 1 Chemical structural formula of Berberine (BBR). frontiersin.org Feng et al., 2015; Cani, 2019).”
BackgroundBerberine-induced bioactive metabolites of the gut microbiota improve energy metabolism
Wang, Y., Shou, J., Li, X., Zhao, Z., Fu, J., He, C., Feng, R., Ma, C., Wen, B., Guo, F., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.02.003 · Cited by 206 · see citing works
Wu, M., Yang, S., Wang, S., Cao, Y., Zhao, R., Li, X., Xing, Y., & Liu, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00223 · Cited by 201 · cited 1× · see citing works
“(Wu et al., 2020) studied the effects of berberine on atherosclerosis and gut microbiota regulation in ApoE (-/-) mice fed a high-fat diet, after treatment with BBR, atherosclerotic lesions was decreased and it significantly reduces total cholesterol, and very low-density lipoprotein cholesterol levels.”
Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., et al. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.106617 · Cited by 199 · cited 2× · see citing works
“Previous reports have indicated that BBR treatment can increase the transforming of cholesterol to bile acid and reduce the level of cholesterol in the blood (Sun et al., 2017), and it affects the metabolism of hepatic lipids and cholesterol by increasing bile acid excretion into the large intestine (Mcdonald et al.”
BackgroundArcher, B. J., Johnson, S. K., Devereux, H., & Baxter, A. L. (2004) · British Journal Of Nutrition · doi:10.1079/bjn20031088 · Cited by 192 · see citing works
Ma, X., Chen, Z., Wang, L., Wang, G., Wang, Z., Dong, X., Wen, B., & Zhang, Z. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00782 · Cited by 189 · cited 1× · see citing works
“It can regulate and ameliorate glycolipid metabolism (Ma et al., 2018; Yu et al., 2019; Bertuccioli et al., 2020), lose weight (Neyrinck et al.”
BackgroundEffects and mechanisms of berberine in diabetes treatment
Yin, J., Ye, J., & Jia, W. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.06.003 · Cited by 183 · cited 1× · see citing works
“Meanwhile, numerous experimental studies have shown that BBR ameliorate body metabolic dysfunction through multiple mechanisms (Yin et al., 2012; Ilyas et al., 2020).”
BackgroundLiu, D., Meng, X. W., Wu, D., Qiu, Z., & Luo, H. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00009 · Cited by 174 · cited 2× · see citing works
“, 2004), pain‐relieving (Hashemzaei and Rezaee, 2021), anti-infective (Aswathanarayan and Vittal, 2018), antitumor (Liu et al., 2019),neuroprotective (Luo et al.”
BackgroundHul, M. V., Geurts, L., Plovier, H., Druart, C., Everard, A., Ståhlman, M., Rhimi, M., Chira, K., Teissèdre, P., Delzenne, N. M., et al. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00107.2017 · Cited by 170 · see citing works
Harsch, I. A., & Konturek, P. C. (2018) · Medical Sciences · doi:10.3390/medsci6020032 · Cited by 169 · cited 1× · see citing works
“In recent years, with the continuous unraveling of the interactions between gut microbiome and organismal metabolism, relevant intervention mechanisms including the regulation of short chain fatty acids, bile acid metabolic pathways, LPS/TLR4 signaling have been gradually studied (Harsch and Konturek, 2018).”
BackgroundGut microbiota composition correlates with changes in body fat content due to weight loss
Remely, M., Tesar, I., Hippe, B., Gnauer, S., Rust, P., & Haslberger, A. G. (2015) · Beneficial Microbes · doi:10.3920/bm2014.0104 · Cited by 162 · cited 1× · see citing works
“muciniphila and markers associated with metabolic disorders (Remely et al., 2015).”
BackgroundXu, X., Gao, Z., Yang, F., Yang, Y., Chen, L., Lin, H., Zhao, N., Xu, J., Wang, X., Ma, Y., et al. (2020) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2019.09.007 · Cited by 156 · see citing works
Self-citationThe effect of Berberine on weight loss in order to prevent obesity: A systematic review
Ilyas, Z., Perna, S., Al-thawadi, S., Alalwan, T. A., Riva, A., Petrangolini, G., Gasparri, C., Infantino, V., Peroni, G., & Rondanelli, M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110137 · Cited by 143 · cited 1× · see citing works
“Meanwhile, numerous experimental studies have shown that BBR ameliorate body metabolic dysfunction through multiple mechanisms (Yin et al., 2012; Ilyas et al., 2020).”
BackgroundEhteshamfar, S. M., Akhbari, M., Afshari, J. T., Seyedi, M., Nikfar, B., Moghaddam, A. S., Ghanbarzadeh, E., & Momtazi‐Borojeni, A. A. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16049 · Cited by 138 · cited 1× · see citing works
“Reported data reveal that BBR can directly suppress functions and differentiation of pro-inflammatory Th1 and Th17 cells, and indirectly decrease Th cell-mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as CD4+ Foxp3+ T regulatory (Tregs), dendritic cells (D…”
BackgroundHe, K., Hu, Y., Ma, H., Zou, Z., Xiao, Y., Yang, Y., Feng, M., Li, X., & Ye, X. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.06.006 · Cited by 137 · see citing works
Ridlon, J. M., Devendran, S., Alves, J. M. P., Doden, H. L., Wolf, P. G., Pereira, G. V., Ly, L. K., Volland, A., Takei, H., Nittono, H., et al. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1618173 · Cited by 137 · cited 1× · see citing works
“hiranonis that are capable of turning taurine-conjugated bile acids into unconjugated bile acids and secondary bile acids such as ursodeoxycholic acid and lithocholic acid (Ridlon et al., 2020).”
BackgroundBerberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway
Liu, D., Zhang, Y., Liu, Y., Hou, L.-Q., Li, S., Tian, H., & Zhao, T.-Y. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0043-125066 · Cited by 136 · cited 1× · see citing works
“A study showed that BBR set-back these effects and restrained LPSinduced TLR4/TNF-a activation, leading to increased insulin receptor and insulin receptor substrate-1 expression in the liver and reduce insulin resistance (Liu et al., 2018).”
BackgroundGut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine
Wang, Y., Tong, Q., Shou, J.-W., Zhao, Z.-X., Li, X.-Y., Zhang, X.-F., Ma, S.-R., He, C.-Y., Lin, Y., Wen, B.-Y., et al. (2017) · Theranostics · doi:10.7150/thno.18290 · Cited by 131 · see citing works
Targeting gut microbiota for precision medicine: Focusing on the efficacy and toxicity of drugs
Feng, W., Liu, J., Ao, H., Yue, S., & Peng, C. Y. (2020) · Theranostics · doi:10.7150/thno.47289 · Cited by 127 · cited 1× · see citing works
“, 2017; Greenhill, 2018; Guerre, 2020; Philippe, 2020), and at the same time, the gut microbiota can be mediated by drugs that regulate the body’s metabolism and play a role in improving metabolic disorders (Feng et al., 2020).”
BackgroundMycotoxin and Gut Microbiota Interactions
Guerre, P. (2020) · Toxins · doi:10.3390/toxins12120769 · Cited by 126 · cited 2× · see citing works
“…antibiotics (Ianiro et al., 2016; Ramirez et al., 2020), and other factors can lead to gut microbiota dysbiosis (Jin et al., 2017; Greenhill, 2018; Guerre, 2020; Philippe, 2020), and at the same time, the gut microbiota can be mediated by drugs that regulate the body’s metabolism and play a role…”
BackgroundModulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies
Yu, Y., Liu, L., Wang, X., Liu, X., Liu, X., Xie, L. Y., & Wang, G. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.11.017 · Cited by 123 · cited 1× · see citing works
“Previous studies (Lu et al., 2009; Yu et al., 2010) showed that that BBR increased the number of L-cells and the mRNA expression levels of proglucagon in the ileum, while promoting GLP-1 secretion in normal and diabetic rats.”
BackgroundZhang, Q., Piao, X., Piao, X., Lu, T., Wang, D., & Kim, S. W. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.09.032 · Cited by 120 · cited 1× · see citing works
“Another study (Zhang et al., 2011) showed that BBR significantly reduced intestinal injury induced by LPS injury rat model and decreased serum levels of downstream inflammatory cytokines.”
BackgroundSelf-citationCounter-Regulatory Role of Bile Acid Activated Receptors in Immunity and Inflammation
Fiorucci, S., Cipriani, S., Mencarelli, A., Renga, B., Distrutti, E., & Baldelli, F. (2010) · Current Molecular Medicine · doi:10.2174/1566524011009060579 · Cited by 119 · cited 1× · see citing works
“Bile acids (BAs) are well known to be important metabolic and inflammatory signaling molecules that modulate lipid and energy-related nuclear hormone receptors, including farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5 or GPBAR1) (Fiorucci et al., 2010).”
BackgroundThe role of gut microbiota in human obesity: Recent findings and future perspectives
Tagliabue, A., & Elli, M. (2013) · Nutrition, Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2012.09.002 · Cited by 118 · cited 1× · see citing works
“Gut microbial Dysbiosis affects the integrity of the intestinal epithelium and increases blood levels of LPS (Cani and Delzenne, 2009; Tagliabue and Elli, 2013).”
BackgroundBerberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats
Gong, J., Hu, M., Huang, Z., Fang, K., Wang, D., Chen, Q., Li, J., Yang, D., Zou, X. G., Xu, L., et al. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00042 · Cited by 116 · see citing works
Tabeshpour, J., Imenshahidi, M., & Hosseinzadeh, H. (2017) · Europe PMC (PubMed Central) · doi:10.22038/ijbms.2017.8682 · Cited by 115 · cited 1× · see citing works
“Berberine (BBR) is a quaternary ammonium salt from the group of bioactive isoquinoline alkaloids (Imenshahidi and Hosseinzadeh, 2016), which is the major active component of traditional Chinese herb Coptis chinensis (Tabeshpour et al., 2017).”
BackgroundEffects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review
Zhang, C., Sheng, J., Li, G., Zhao, L., Wang, Y., Yang, W., Yao, X., Sun, L., Zhang, Z., & Cui, R. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01461 · Cited by 114 · cited 2× · see citing works
“…host metabolism and its abundance is often inversely correlated with metabolic disturbances in most preclinical and clinical studies (Zhou and Zhang, 2019), some studies made known a negative correlation among A. muciniphila and markers associated with metabolic disorders (Remely et al.,…”
BackgroundRomijn, J. A., Corssmit, E. P. M., Havekes, L. M., & Pijl, H. (2008) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328302c9b0 · Cited by 112 · see citing works
Short Chain Fatty Acids, pancreatic dysfunction and type 2 diabetes
Mandaliya, D. K., & Seshadri, S. (2019) · Pancreatology · doi:10.1016/j.pan.2019.01.021 · Cited by 112 · see citing works
Lu, S.-S., Yu, Y.-L., Zhu, H., Liu, X., Liu, L., Liu, Y.-W., Wang, P., Xie, L. Y., & Wang, G.-J. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0419 · Cited by 111 · cited 1× · see citing works
“Previous studies (Lu et al., 2009; Yu et al., 2010) showed that that BBR increased the number of L-cells and the mRNA expression levels of proglucagon in the ileum, while promoting GLP-1 secretion in normal and diabetic rats.”
BackgroundBai, J., Zhu, Y. G., & Dong, Y. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.10.043 · Cited by 110 · cited 1× · see citing works
“Enterobacter, Vibrio desulfuricus and Enterobacter cloacae increase significantly in the state of metabolic disorder, and then cause metabolic diseases (Bai et al., 2016).”
BackgroundAswathanarayan, J. B., & Vittal, R. R. (2018) · RSC Advances · doi:10.1039/c8ra06413j · Cited by 96 · cited 1× · see citing works
“, 2004), pain‐relieving (Hashemzaei and Rezaee, 2021), anti-infective (Aswathanarayan and Vittal, 2018), antitumor (Liu et al.”
Caliceti, C., Franco, P., Spinozzi, S., Roda, A., & Cicero, A. F. G. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160411143314 · Cited by 91 · cited 1× · see citing works
“Its mechanism of utility has also been extensively and intensively studied (Caliceti et al., 2016), a large number of experimental studies have shown that berberine alleviates body metabolism and insulin resistance through a variety of mechanisms, such as amelioration of oxidative stress, inhibition of macrophage infl…”
BackgroundSun, H., Wang, N., Cang, Z., Zhu, C., Zhao, L., Nie, X., Cheng, J., Xia, F., Zhai, H., & Lu, Y. (2016) · Obesity Facts · doi:10.1159/000449507 · Cited by 90 · cited 3× · see citing works
“, 2016), regulating the bacteria-brain-gut axis (Sun et al., 2016; Sun et al., 2017), strengthening intestinal barrier function (Zhang et al.”
BackgroundXu, J. H., Liu, X., Pan, W., & Zou, D. J. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6321 · Cited by 86 · see citing works
Higher circulating bile acid concentrations in obese patients with type 2 diabetes
Vincent, R. P., Omar, S., Ghozlan, S., Taylor, D. R., Cross, G. F., Sherwood, R. A., Fändriks, L., Olbers, T., Werling, M., Alaghband‐Zadeh, J., et al. (2013) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563212473450 · Cited by 84 · see citing works
Is serum Interleukin-17 associated with early atherosclerosis in obese patients?
Tarantino, G., Costantini, S., Finelli, C., Capone, F., Guerriero, E., Sala, N. L., Gioia, S., & Castello, G. (2014) · Journal of Translational Medicine · doi:10.1186/s12967-014-0214-1 · Cited by 83 · cited 1× · see citing works
“Atherosclerosis (AS) is the main co-morbidity of metabolic syndrome, research lends credence to a possible indirect role of IL-17 in determining or favoring early (Tarantino et al., 2014).”
BackgroundGu, S., Cao, B., Sun, R., Tang, Y., Paletta, J. L., Wu, X., Liu, L., Zha, W., Zhao, C., Li, Y., et al. (2014) · Molecular BioSystems · doi:10.1039/c4mb00500g · Cited by 82 · cited 1× · see citing works
“The study distinctly shows that BBR remarkably increased the Firmicutes/Bacteroidetes ratio and suggests that this is one of the mechanisms of its induced serum free bile acid increase and lipid lowering effect (Gu et al., 2015).”
BackgroundFeng, R., Zhao, Z., Ma, S.-R., Guo, F., Wang, Y., & Jiang, J.-D. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00214 · Cited by 78 · cited 2× · see citing works
“It can be seen that the hypolipidemic effect of BBR may be related to its up-regulation of SREBP2 and CYP7A1 expression and promotion of bile acid metabolism (Feng et al., 2018).”
BackgroundPérez, M. M., Martins, L. M. S., Dias, M. S., Pereira, C. A., Leite, J. A., Gonçalves, E. C. S., de Almeida, P. Z., de Freitas, E. N., Tostes, R. C., Ramos, S. G., et al. (2018) · Immunology · doi:10.1111/imm.13028 · Cited by 76 · see citing works
Dong, C., Yu, J., Yang, Y., Zhang, F., Su, W., Fan, Q., Wu, C., & Wu, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111595 · Cited by 76 · cited 1× · see citing works
“muciniphila in a host-dependent way (Dong et al., 2021).”
Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients
Kallio, K., Buhlin, K., Jauhiainen, M., Keva, R., Tuomainen, A. M., Klinge, B., Gustafsson, A. K., & Pussinen, P. J. (2008) · Innate Immunity · doi:10.1177/1753425908095130 · Cited by 72 · cited 1× · see citing works
“It plays an important role in both acute infections and chronic infections (Kallio et al., 2008).”
BackgroundDose-response effect of berberine on bile acid profile and gut microbiota in mice
Guo, Y., Zhang, Y., Huang, W., Selwyn, F. P., & Klaassen, C. D. (2016) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-016-1367-7 · Cited by 69 · see citing works
Zou, Z., Hu, Y., Ma, H., Wang, Y.-Z., He, K., Xia, S., Wu, H., Xue, D., Li, X., & Ye, X. (2015) · Fitoterapia · doi:10.1016/j.fitote.2015.06.005 · Cited by 68 · see citing works
Traditional Chinese Medicine and Gut Microbiome: Their Respective and Concert Effects on Healthcare
Zhang, R., Gao, X., Bai, H., & Ning, K. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00538 · Cited by 68 · cited 3× · see citing works
“, 2012) and modulate energy metabolism, which can be used to treat cancer (Zhang et al., 2020), digestive (Zou et al.”
BackgroundInfluentialLi, C.-N., Wang, X., Lei, L., Liu, M., Li, R., Sun, S., Liu, S., Huan, Y., Zhou, T., Liu, Q., et al. (2019) · Phytotherapy Research · doi:10.1002/ptr.6588 · Cited by 61 · cited 2× · see citing works
“A study showed that berberine compound increased the relative abundance of Proteobacteria and decreased Firmicutes and TM7 enrichment, which accelerate conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA) in ob/ob mice, and DCA upregulated colonic TGR5 expression and GLP sec…”
BackgroundCui, H., Hu, Y., Li, J., Yuan, K., & Guo, Y. (2018) · Molecules · doi:10.3390/molecules24010103 · Cited by 59 · cited 1× · see citing works
“From administration to absorption, BBR can be metabolized by gut microbiota to improve its therapeutic effects on metabolism related diseases such as diabetes, hyperlipidemia, or directly affect gut microbiota to regulate and ameliorate metabolic disorders (Cui et al., 2018).”
BackgroundDevendran, S., Shrestha, R., Alves, J. M. P., Wolf, P. G., Ly, L. K., Hernández, Á. G., Méndez–García, C., Inboden, A. M., Wiley, J., Paul, O., et al. (2019) · Applied and Environmental Microbiology · doi:10.1128/aem.00052-19 · Cited by 59 · see citing works
Wang, Y., Liu, H., Zheng, M., Yang, Y., Ren, H., Kong, Y., Wang, S., Wang, J., Jiang, Y., Yang, J., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.609134 · Cited by 59 · cited 4× · see citing works
“Other studies have also shown (Xu et al., 2017) BBR significantly increased the levels of plasma GLP-1 and GLP-2 in portal vein, as well as the number of L-cells in proximal colon and the mRNA expression level of preluganin.”
BackgroundInfluentialCould the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?
Finelli, C. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i44.16649 · Cited by 58 · see citing works
A review on pain‐relieving activity of berberine
Hashemzaei, M., & Rezaee, R. (2020) · Phytotherapy Research · doi:10.1002/ptr.6984 · Cited by 56 · cited 1× · see citing works
“, 2004), pain‐relieving (Hashemzaei and Rezaee, 2021), anti-infective (Aswathanarayan and Vittal, 2018), antitumor (Liu et al.”
Shinkov, A. D., Borissovа, A.-M., Kovatcheva, R. D., Vlahov, J. D., Dakovska, L. N., Atanassova, I., & Petkova, P. (2017) · Postgraduate Medicine · doi:10.1080/00325481.2018.1410054 · Cited by 55 · cited 1× · see citing works
“The current situation shows that a large proportion of metabolic syndrome patients suffer from impaired glucose tolerance or diabetes (Shinkov et al., 2018).”
BackgroundZhou, J., & Zhang, X. (2019) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(19)30101-3 · Cited by 55 · see citing works
Biotransformation of 1‐Nitropyrene in Intestinal Anaerobic Bacteria
Kinouchi, T., Manabe, Y., Wakisaka, K., & Ohnishi, Y. (1982) · Microbiology and Immunology · doi:10.1111/j.1348-0421.1982.tb00249.x · Cited by 53 · cited 8× · see citing works
“Treatment with berberine in combination with Bifidobacterium could increase the abundance of beneficial bacteria in the intestine of diabetic patients and achieve better glucose lowering effect because of the inhibitory effect of berberine on Bifidobacterium (Ming et al., 2021).”
BackgroundInfluentialSchapiro, J. M., Gupta, R., Stefansson, E., Fang, F. C., & Limaye, A. P. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.9.4127-4129.2004 · Cited by 52 · cited 9× · see citing works
“Increasing of the NR-producing bacteria: BBR can increase th abundance of Bacteroides, Escherichia-Shigella and Bifidobacterium which can produc NRs. Nrs converts BBR into its absorbable form of DhBBR, which has highly polar and easily absorbed into the blood.”
BackgroundInfluentialMing, J., Yu, X., Xu, X., Wang, L., Ding, C., Wang, Z., Xie, X., Li, S., Yang, W., Luo, S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00942-7 · Cited by 52 · see citing works
Gao, Z., Li, Q., Wu, X., Zhao, X., Zhao, L., & Tong, X. (2017) · Journal of Immunology Research · doi:10.1155/2017/1813086 · Cited by 50 · cited 1× · see citing works
“, 2017a), alleviating metabolic endotoxemia (Gao et al., 2017), increasing of short-chain fatty acid (SCFA)producing bacteria (Mcnabney and Henagan, 2017) and other ways.”
BackgroundSelf-citationGu, S., Cao, B., Sun, R., Tang, Y., Paletta, J. L., Wu, X., Liu, L., Zha, W., Zhao, C., Li, Y., et al. (2014) · Molecular BioSystems · doi:10.1039/c4mb90042a · Cited by 49 · see citing works
Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3
Zhang, B., Pan, Y., Xu, L., Tang, D., Dorfman, R. G., Zhou, Q., Yin, Y., Yang, L., Zhou, L., Zhao, S., et al. (2018) · Endocrine · doi:10.1007/s12020-018-1689-y · Cited by 49 · see citing works
Han, K., Bose, S., Wang, J., Lim, S.-K., Chin, Y., Kim, Y., Choi, H., & Kim, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182467 · Cited by 47 · cited 2× · see citing works
“BBR is considered to be an agonist of FXR and TGR5 and regulate bile acid signal and function (Han et al., 2017).”
Berberine reduced blood pressure and improved vasodilation in diabetic rats
Ma, Y., Liang, L., Zhang, Y.-B., Wang, B., Bai, Y., Dai, Z.-J., Xie, M., & Wang, Z. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0014 · Cited by 45 · see citing works
Cao, H., Li, C., Lei, L., Wang, X., Liu, S., Liu, Q., Huan, Y., Sun, S., & Shen, Z. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.578943 · Cited by 45 · cited 1× · see citing works
“The researchers found that BBR reversed these increases and reduced the level of Vibrio desulfuricus, in addition, they discovered that BBR treatment reduced inflammation of KKAy mice at least in part by regulating TLR4, ERK, and p38MAPK pathways (Cao et al., 2020).”
BackgroundWęglarz, L., Wawszczyk, J., Orchel, A., Jaworska‐Kik, M., & Dzierżewicz, Z. (2006) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9320-0 · Cited by 44 · cited 7× · see citing works
“Decreasing of LPS-producing bacteria: BBR reduced the level of Vibrio desulfuricus and Enterobacter to inhibit the production of LPS.”
BackgroundInfluentialPrebiotic Effect of Berberine and Curcumin Is Associated with the Improvement of Obesity in Mice
Neyrinck, A. M., Sánchez, C. R., Rodriguez, J., Cani, P. D., Bindels, L. B., & Delzenne, N. M. (2021) · Nutrients · doi:10.3390/nu13051436 · Cited by 44 · cited 1× · see citing works
“, 2020), lose weight (Neyrinck et al., 2021) and alleviation of insulin resistance (Memon et al.”
BackgroundLi, M., Zhou, W., Dang, Y., Li, C., Ji, G., & Zhang, L. R. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110953 · Cited by 40 · see citing works
Yang, S., Li, D., Yu, Z., Li, Y., & Wu, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.709629 · Cited by 40 · cited 6× · see citing works
“Then, different conclusions remain to be reported about the structural changes of intestinal flora caused by Berberine: Some believe that the abundance of Akkermansia increased after BBR intervention, But while others believe that BBR could not increase the abundance of Akkermansia alone.”
BackgroundInfluentialGetting to the bottom of feeding behaviour: who’s on top?
Cameron, J. D., & Doucet, É. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h06-072 · Cited by 36 · see citing works
Berberine alters gut microbial function through modulation of bile acids
Wolf, P. G., Devendran, S., Doden, H. L., Ly, L. K., Moore, T., Takei, H., Nittono, H., Murai, T., Kurosawa, T., Chlipala, G. E., et al. (2021) · BMC Microbiology · doi:10.1186/s12866-020-02020-1 · Cited by 34 · cited 1× · see citing works
“(Wolf et al., 2021) found that sulfated bile acids were strongly associated with C.”
BackgroundWang, S., Zhang, X., Cai, B., & Chen, Q. (2020) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530320666200910105612 · Cited by 33 · see citing works
Luo, T., Jiang, W. M., Kong, Y., Li, S., He, F., Xu, J., & Wang, H. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311211080013 · Cited by 30 · cited 1× · see citing works
“, 2019),neuroprotective (Luo et al., 2012) and modulate energy metabolism, which can be used to treat cancer (Zhang et al.”
BackgroundSelf-citationMethylglyoxal and insulin resistance in berberine-treated type 2 diabetic patients
Memon, M., Khan, R., Riaz, S., Ain, Q., Ahmed, M., & Kumar, N. (2018) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_1078_17 · Cited by 29 · cited 1× · see citing works
“, 2021) and alleviation of insulin resistance (Memon et al., 2018), especially in the treatment of combined multiple metabolic disorders, the efficacy of BBR is outstanding (Yu-Guang et al.”
BackgroundMartini, D., Pucci, C., Gabellini, C., Pellegrino, M., & Andreazzoli, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-73661-5 · Cited by 25 · cited 1× · see citing works
“, 2021), cardiovascular (Martini et al., 2020), and neurological diseases (Kulkarni and Dhir, 2010).”
BackgroundBertuccioli, A., Moricoli, S., Amatori, S., Rocchi, M., Vici, G., & Sisti, D. (2019) · Journal of Medicinal Food · doi:10.1089/jmf.2019.0088 · Cited by 23 · cited 1× · see citing works
“It can regulate and ameliorate glycolipid metabolism (Ma et al., 2018; Yu et al., 2019; Bertuccioli et al., 2020), lose weight (Neyrinck et al.”
BackgroundHvistendahl, M. (2012) · Science · doi:10.1126/science.336.6086.1248 · Cited by 22 · cited 1× · see citing works
“With further in-depth studies scholars have found that modulation of gut microbiome may be another novel mechanism of action for berberine to ameliorate metabolic disorders (Hvistendahl, 2012; Feng et al., 2015).”
BackgroundSingh, A. B., & Liu, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-52253-y · Cited by 21 · cited 1× · see citing works
“, 2016a) and upregulation of Trib1 mRNA levels to reduce lipid levels (Singh and Liu, 2019).”
BackgroundXiao, Y., Xu, M., Alimujiang, M., Bao, Y., Wei, L., & Yin, J. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27312 · Cited by 16 · cited 1× · see citing works
“In terms of glucose metabolism, BBR strengthened autophagy and protected from high glucose-related injury in podocytes by promoting the AMPK activation, at the same time, the bidirectional regulation of AMPK activity can reduce the risk of hypoglycemia caused by berberine (Xiao et al., 2018).”
BackgroundCao, S., Yu, S., Cheng, L., Yan, J., Zhu, Y., Deng, Y., Qiu, F., & Kang, N. (2018) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2018.09.007 · Cited by 11 · see citing works
Live and Diet by Your Gut Microbiota
Bassis, C. M. (2019) · mBio · doi:10.1128/mbio.02335-19 · Cited by 10 · see citing works
Responses of human gut microbiota abundance and amino acid metabolism in vitro to berberine
Fu, Y., Wang, Y., Wang, X., Sun, Y., Ren, J., & Fang, B. (2022) · Food & Function · doi:10.1039/d1fo04003k · Cited by 10 · cited 1× · see citing works
“However, experiments in humans have also shown that BBR reduces acetate and propionate production but has no effect on butyrate levels, and that, at the same time, the use of BBR increases the abundance of Faeca l ibacter ium and decreases the abundance of Bifidobacterium, Streptococcus and Enterococcus (Fu et al., 20…”
BackgroundTranscriptional profile induced by furazolidone treatment of Shigella flexneri
Fu, H., Leng, W., Wang, J., Zhang, W., Peng, J., Wang, L., & Jin, Q. (2007) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-007-1180-9 · Cited by 9 · cited 5× · see citing works
“, 2004), Escherichia-Shigella (Fu et al., 2007), and Bifidobacterium (Kinouchi et al.”
InfluentialExercise affects gut microbiota and bone
Greenhill, C. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0014-4 · Cited by 7 · see citing works
The Direct Thrombin Inhibitor Trialists’ Collaborative Group (2002) · ACC Current Journal Review · doi:10.1016/s1062-1458(02)00683-9 · Cited by 4 · see citing works
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Editorial: Gastrointestinal Hormones
Paternoster, S., Keating, D. J., & Falasca, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00498 · Cited by 1 · cited 3× · see citing works
“In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NA…”
Background
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Research works printed but not linked: 3
- Gong J. Hu M. Huang Z. Fang K. Wang D. Chen Q.. (2017b). Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats. Front. Pharmacol. 8. doi: 10.3389/fphar.2017.00042 PMC5290458 28217099 · DOI
- He K. Hu Y. Ma H. Zou Z. Xiao Y. Yang Y.. (2016b). Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways. Biochim. Biophys. Acta 1862 (9), 1696– 1709. doi: 10.1016/j.bbadis.2016.06.006 27287254 · DOI
- Xu X. Gao Z. Yang F. Yang Y. Chen L. Han L.. (2020b). Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine. Genomics Proteomics Bioinf. 18 (6), 721– 736. doi: 10.1016/j.gpb.2019.09.007 PMC8377040 33359679 · DOI
Cited by
Sorted by citations
Bicknell, B. T., Liebert, A. D., Borody, T. J., Herkes, G., McLachlan, C. S., & Kiat, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119577 · Cited by 129 · see citing works
“Improvements in the microbiome include increases in the numbers of SCFA-producing bacteria and mucin-degrading bacteria ( Akkermansia ) [448,449] and decreases in LPS bacteria (Proteobacteria and Desulfovibrio ) [425].”
Ashraf, M. V., Khan, S., Misri, S., Gaira, K. S., Rawat, S., Rawat, B., Khan, M. A. H., Shah, A. A., Asgher, M., & Ahmad, S. (2024) · Pharmaceuticals · doi:10.3390/ph17080975 · Cited by 102 · see citing works
Obesity: pathophysiology and therapeutic interventions
Kong, Y., Yang, H., Nie, R., Zhang, X., Zuo, F., Zhang, H., & Nian, X. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00264-9 · Cited by 89 · see citing works
“…composition: BBR restores the Bacteroidetes/Firmicutes balance, enriches SCFA-producing bacteria, and suppresses bacterial proliferation [351, 353–360]. b Enhancement of intestinal barrier integrity: BBR modulates the abundance of Akkermansia muciniphila and the IL-25/mucin-2 dynamics [361, 362].”
Self-citationBerberine influences multiple diseases by modifying gut microbiota
Yang, F., Gao, R., Luo, X., Liu, R., & Xiong, D. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1187718 · Cited by 70 · see citing works
“This promotes insulin secretion, improves insulin resistance, and inhibits lipogenesis which is associated with changes in the composition of the gut microbiota and its metabolites [(1, 8, 9)].”
BackgroundRepairing gut barrier by traditional Chinese medicine: roles of gut microbiota
Zhou, Y., Zhang, D., Cheng, H., Wu, J., Liu, J., Feng, W., & Peng, C. Y. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1389925 · Cited by 57 · see citing works
Chen, K., Wang, H., Yang, Y., Tang, C., Sun, X., Zhou, J., Liu, S., Li, Q., Zhao, L., & Gao, Z. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02299-5 · Cited by 45 · see citing works
“BBR markedly increases the abundance of the genus Lacto-bacillus, Bifidobacterium, Blautia, Faecalibacterium, Roseburia, Ruminococcus, Clostridium, Akkermansia and decrease the abundance of harmful genera such as Escherichia coli during anti-diabetes [170].”
Self-citationPharmacological properties and therapeutic potential of berberine: a comprehensive review
Fan, K.-Q., Zhang, L., Song, F., Zhang, Y., Chen, T., Cheng, X., Su, N., Zou, Y., Yu, T., Tan, F., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1604071 · Cited by 33 · see citing works
Yang, B. J., Han, X., Liu, D., Tan, Z., & Deng, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1072376 · Cited by 29 · see citing works
Al-Marzooqi, S. K., Almarzooqi, F., Sadida, H. Q., Jerobin, J., Ahmed, I., Abou‐Samra, A., Fakhro, K. A., Dhawan, P., Bhat, A. A., & Akil, A. A. (2024) · Obesity Reviews · doi:10.1111/obr.13766 · Cited by 30 · see citing works
“233,234 Phytochemicals modulate the gut microbiota by selectively promoting or inhibiting specific bacterial groups, thereby altering metabolite production (e.g., short-chain fatty acids, bile acids, and polyphenols) and influencing bacterial gene expression and enzyme activities.”
Kong, Y., Yang, H., Nie, R., Zhang, X., Zhang, H., & Nian, X. (2025) · European journal of medical research · doi:10.1186/s40001-025-02738-6 · Cited by 40 · see citing works
“…barrier function through: (1) Mucosal protection: Ameliorates endoplasmic reticulum (ER) stress-induced goblet cell apoptosis by restraining mucin-2 expression, upregulating Akkermansia muciniphil a ( A. muciniphila ) abundance to stabilize tight junctions in obese and diabetic mice [165–167].”
Self-citationFiore, G., Pascuzzi, M. C., Profio, E. D., Corsello, A., Agostinelli, M., Mendola, A. L., Milanta, C., Campoy, C., Calcaterra, V., Zuccotti, G., et al. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106599 · Cited by 28 · see citing works
Wang, C., Yang, Y., Chen, J., Dai, X., Xing, C., Zhang, C., Cao, H., Guo, X., Hu, G., & Zhuang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417304 · Cited by 27 · see citing works
“Recent research has indicated that BBR may directly improve the function of the intestinal barrier, reduce inflammation, control the bile acid signal pathway, and regulate the axis of bacteria–gut–brain [39].”
BackgroundMulti-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus
He, Q., Dong, H., Guo, Y., Gong, M., Xia, Q., Lu, F., & Wang, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1074348 · Cited by 26 · see citing works
“BBR can significantly reduce the abundance of Proteobacteria, (such as Desulfovibrio, and Enterobacter cloacae), and inhibit LPS production, as well as prevent serum LPS elevation, regulating intestinal permeability, attenuating insulin resistance and improving metabolic endotoxemia effectively (101).”
BackgroundVrentzos, E., Pavlidis, G., Korakas, E., Kountouri, A., Pliouta, L., Dimitriadis, G., & Lambadiari, V. (2025) · Nutrients · doi:10.3390/nu17101657 · Cited by 25 · see citing works
“Berberine, a natural alkaloid found in Coptis chinensis, has been used for thousands of years in traditional Chinese medicine to treat gastrointestinal disorders, infections, and metabolic imbalances [26].”
Advancements in MRSA treatment: the role of berberine in enhancing antibiotic therapy
Zhou, F., Gu, X., Wang, W., Lin, M., & Wang, L. (2024) · BMC Microbiology · doi:10.1186/s12866-024-03692-9 · Cited by 21 · see citing works
Liu, Y., Wang, H., Geng, Y.-H., Han, L., Tu, S., & Wang, H. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1112088 · Cited by 19 · see citing works
“Author ID Year Country Model Targeted molecular Mechanism Limei Liu 2015 China Spontaneously hypertensive rats eIF2a, ATF3, ATF6, XBP1, COX-2, and ROS↓ Activating AMPK, thus inhibiting ER stress and scavenging ROS Zhichao Wang 2022 China Angiotensin II-induced hypertensive mice FMO3 and TMA/TMAO↓ Regulating the gut mi…”
BackgroundSelf-citationGut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke
Gao, L., Xia, X., Shuai, Y., Zhang, H., Jin, W., Zhang, X., & Zhang, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1164150 · Cited by 20 · see citing works
Self-citationLiu, M., Shi, W., Huang, Y., Wu, Y., & Ke-ming, W. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1134430 · Cited by 18 · see citing works
Gut microbiota and the “gut-liver-kidney axis” theory: from mechanisms to therapeutics
Fei, D.-L., Liu, Y., Liu, J., Yu, Z., & Dong, J.-L. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1554458 · Cited by 16 · see citing works
“For instance, research has demonstrated gut microbiome can influence how various medications are processed in the body, resulting in varying therapeutic outcomes for different patients (Lim and Wang, 2022).”
Tian, Y., Yao, J., Gao, Q., Zou, L., Lu, P., Guan, T., Liu, X., Zhou, S., & Jin, X. (2025) · Chinese Medicine · doi:10.1186/s13020-025-01269-w · Cited by 16 · see citing works
“On the other hand, berberine itself reshapes gut microbial composition, restores dysbiosis, strengthens the intestinal barrier, and reduces metabolic inflammation and endotoxemia [94].”
Effect of tea polyphenols on the prevention of neurodegenerative diseases through gut microbiota
Xu, L., Wang, R., Liu, Y., Zhan, S., Wu, Z., & Zhang, X. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105669 · Cited by 15 · see citing works
Ma, W., Wang, M., Chen, J., Wang, Y., Chen, J., Pei, Y., Gong, Y., You, J., Cao, Y., Zhou, J., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156723 · Cited by 14 · see citing works
Lu, Y., Sun, W., Zhang, Z., Yu, J. H., Zhang, J., & Guo, Q. (2025) · Food Bioscience · doi:10.1016/j.fbio.2025.105848 · Cited by 14 · see citing works
Chen, C.-Y., & Zhang, Y. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117475 · Cited by 14 · see citing works
Janota, B., Janion, K., Buzek, A., & Janczewska, E. (2025) · Metabolites · doi:10.3390/metabo15080528 · Cited by 13 · see citing works
Čolić, M., Pavelić, S. K., Peršurić, Ž., Agaj, A., Bulog, A., & Pavelić, K. (2024) · Redox Report · doi:10.1080/13510002.2024.2333619 · Cited by 13 · see citing works
“Chitosan combination with small anionic molecules such as citric or ascorbic acid form nano-gels that are also very e ffi cient delivery systems [91].”
BackgroundDu, L., Yang, D., Wu, L., Li, M., Wu, S., Ba, Y., Bao, Y., Su, R., & Lin, S. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s455600 · Cited by 11 · see citing works
“…are widely present in different medicinal plants, and various ingredients, such as berberine, 33 can reverse disorders in the gut microbiota; 34 thus, they affect the secretion of 5-HT, which is involved in many metabolic pathways, such as nerve active ligand-receptor, cAMP signal pathway,…”
BackgroundBerberine: A natural modulator of immune cells in multiple sclerosis
Yazdanpanah, E., Dadfar, S., Shadab, A., Orooji, N., Nemati, M., Pazoki, A., Esmaeili, S., Baharlou, R., & Haghmorad, D. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1213 · Cited by 10 · see citing works
“15 Interestingly, Berberine appeared to be almost safe in usual doses, with a relatively low incidence of side effects.”
BackgroundRole of anthraquinones in combating insulin resistance
Xia, W., Li, S., Li, L., Zhang, S., Wang, X., Ding, W., Ding, L., Zhang, X., & Wang, Z. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1275430 · Cited by 10 · see citing works
Berberine attenuates TNBS-induced colitis in mice by improving the intestinal microbiota
Li, C., Yin, X., Xie, C., Zeng, J., Song, C., Yang, G., Zhang, J., Chen, S., Wei, P., Wang, Z., et al. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1463005 · Cited by 10 · see citing works
“It can also reduce the inflammatory response in the intestines and preserve the integrity of the intestinal mucosal barrier (Wang H. et al., 2022).”
BackgroundMethodNaseem, S., & Rizwan, M. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.112285 · Cited by 9 · see citing works
Ping, Y., Li, C., Wang, L., & Zhao, H. L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1102605 · Cited by 9 · see citing works
Cervello, M., Augello, G., Cocco, L., Ratti, S., Follo, M. Y., Martelli, A. M., Cusimano, A., Montalto, G., & McCubrey, J. A. (2024) · Advances in Biological Regulation · doi:10.1016/j.jbior.2024.101032 · Cited by 9 · see citing works
Šantić, R., Martinovic, L., Pavlović, N., Martinović, D., Vrdoljak, J., Kumrić, M., Vilović, M., & Božić, J. (2026) · Molecules · doi:10.3390/molecules31111840 · Cited by 7 · see citing works
“…by P-glycoprotein efflux and first-pass metabolism, is partially resolved by microbial conversion to more bioavailable forms, though CYP3A4 inhibition introduces drug interaction risk and gastrointestinal adverse effects above 1.5 g/day remain the primary barrier to standardisation [173,185,187].”
InfluentialLCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine
He, H., Chai, X., Li, J., Li, C., Wu, X., Ye, X., Ma, H., & Li, X. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121595 · Cited by 6 · see citing works
Chang, C., Roh, Y. S., Du, M., Kuo, Y. C., Zhang, Y., Hardy, M. L., Gahler, R. J., & Solnier, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115625 · Cited by 6 · see citing works
Chai, L., Song, Y., Chen, A., Jiang, L., & Deng, H. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.122774 · Cited by 6 · see citing works
Sarkar, A., Khan, A. S., Kaul, R., Lee, S., Kamal, I., Paul, P., Laws, S., & Châari, A. (2024) · Discover Public Health · doi:10.1186/s12982-024-00213-x · Cited by 5 · see citing works
Nie, R., Yuan, Z., Wu, Y., Pan, M., Lu, J., & Xiong, G. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1600408 · Cited by 4 · see citing works
“Furthermore, BBR has shown potential to ameliorate metabolic disorders and mitigate diverse pathologies through gut microbiota modulation (Wang et al., 2022; Yang et al., 2023).”
Amalraj, A., Narayanan, V. A., Ardra, T. S., & Gopi, S. (2025) · In Silico Pharmacology · doi:10.1007/s40203-025-00426-1 · Cited by 3 · see citing works
“…signaling, lowers systemic inflammation, and improves gut microbiota composition by increasing short-chain fatty acid (SCFA)-producing species such as Akkermansia muciniphila while reducing endotoxin-producing strains (Zhang et al. 2015; Zhao et al. 2021 ; Wang et al. 2022 ; Dehau et al. 2023 ).”
Huang, J., Lu, J., Wu, C., Chen, S., Chang, T., Xu, L., Shen, X., Bakhsh, Q., Qin, B., Qian, W., et al. (2025) · Biomolecules · doi:10.3390/biom15111589 · Cited by 3 · see citing works
“The natural product berberine hydrochloride (BH), known for its broad-spectrum antibacterial activity and immunomodulatory properties, has become a potential drug candidate by disrupting bacterial membrane structure, suppressing biofilm formation, and regulating inflammation [11–15].”
A Strainer-Based Platform for the Collection and Immunolabeling of Mouse Intestinal Organoids
Tan, J., Liu, Y., Li, W., Chen, G., Fang, Y., He, X., Fu, B., & Jing, Z. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713568 · Cited by 3 · see citing works
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“Studies have shown that BBR exerts protective effects by modulating the gut microbiota and regulating receptor (TLR-4) associated signaling pathways [8, 9].”
Kurhaluk, N., Mazur, Z., Kołodziejska, R., & TKACZENKO, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083511 · Cited by 3 · see citing works
Swain, M. P., Mehta, C. H., Padya, B. S., Sharma, S., Velagacherla, V., Mitra, A., Mohanty, S., & Mukherjee, T. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02187-5 · Cited by 2 · see citing works
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Managing Glucose Homeostasis Through the Gut Microbiome
Weninger, S. N., Manley, A., & Duca, F. A. (2025) · Annual Review of Physiology · doi:10.1146/annurev-physiol-051524-094728 · Cited by 3 · see citing works
Dumitru, C. N., Marcu, T., Dumitru, A. O., Tudor, S. S., Ferțu, I. D., Elisei, A.-M., & Goroftei, L. (2026) · Pharmaceuticals · doi:10.3390/ph19081313 · Cited by 2 · see citing works
“Therefore, berberine can indirectly influence the disposition of other drugs by at least three routes: altering bacterial drug metabolism, modifying the enterohepatic circuit through regulation of bacterial β -glucuronidases, and modulating gut-barrier integrity [95,104,105].”
InfluentialBerberine Treats Type 2 Diabetes by Regulating Gutmicrobiota
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Exploring the relationship between berberine and the gut microbiome: A closer look at recent studies
Beyazgül, D., & Aksakal, N. E. (2024) · Anadolu Kliniği Tıp Bilimleri Dergisi · doi:10.21673/anadoluklin.1410170 · Cited by 1 · see citing works
Purhematy, A., Sharififar, F., & Halilu, E. M. (2026) · Advanced Gut & Microbiome Research · doi:10.1155/agm3/4722684 · Cited by 1 · see citing works
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“Similarly, important mechanisms attributed to BBR, such as AMPK activation and microbiota-mediated effects, are not represented by the chosen computational target (Fig 7) [24,72–74].”
Kumar, V., Sharma, C., Bhatt, S. C., Rajput, V., Mishra, R., Gupta, A. K., Shikha, D., Kumar, V., & Naik, B. (2026) · Food Production Processing and Nutrition · doi:10.1186/s43014-026-00402-y · Cited by 1 · see citing works
“Some alkaloids, such as berberine, have been found to enhance gut microbiota composition by promoting the growth of beneficial bacteria and inhibiting endotoxin-producing microorganisms, thereby alleviating gut inflammation and supporting metabolic health (Wang et al., 2022; Zhang et al., 2016).”
Liu, Y., Liu, Y.-Y., Xiao, Y., Huang, W., Sun, R., Hu, J., Fu, X., Chuxiao, T., Fu, Q., & Zhao, J. (2025) · Journal of Diabetes Research · doi:10.1155/jdr/3823051
“Berberine, one of the primary active ingredients in SL decoction, exhibits multiple biological activities, including regulation of glucose and lipid homeostasis, anti-in fl ammatory, antioxidant, anticancer properties, and protection of the intestinal barrier [28].”
Gut Ecology and Metabolic Health: Understanding the Microbiome-Metabolic Syndrome Connection
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BERBERINE IN METABOLIC DISORDERS: THE “NATURE’S OZEMPIC” PHENOMENON - A NARRATIVE REVIEW
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“Inter-estingly, this effect differed from that of berberine, which has been reported to preferentially enhance butyrate production [59,60].”
Xie, F.-J., Zhang, M., Li, W.-T., Zhou, W.-Y., Ma, H.-B., Xu, Y., & Bi, L.-M. (2026) · World Journal of Diabetes · doi:10.4239/wjd.122293
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“Changes in microbial composition can be consequences of antimicrobial exposure, altered diet or gastrointestinal adverse effects rather than mediators of improved insulin sensitivity [66–69].”
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“Berberine, an isoquinoline alkaloid, has been shown to activate AMPK and modulate the gut microbiota in DIO mice, resulting in reduced body weight and improved glucose tolerance [38,39].”
- Authors
- Wang, H., Zhang, H., Gao, Z., Zhang, Q., & Gu, C.
- Affiliations
- Beijing University of Chinese Medicine (CN)
- China Academy of Chinese Medical Sciences (CN)
- Guangzhou University of Chinese Medicine (CN)
- Corresponding author
- Gu, Chengjuan
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2022-08-25
- Volume
- 12
- Pages
- 854885-854885
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC9452888
- OpenAlex
- W4293089756
- Cited by
- 69
- References
- 162
- Citations by year
- 2026: 21 · 2025: 19 · 2024: 14 · 2023: 12 · 2022: 3
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81973837, 81704067, 81430097)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- berberine, gut microbiota, metabolic syndrome, obesity, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, intestinal barrier function, inflammation, bile acid signaling, gut-brain axis
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Berberine, Diabetes Mellitus, Type 2, Humans, Non-alcoholic Fatty Liver Disease
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