Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders.

BACKGROUND Berberine, an alkaloid obtained by extraction from Berberis spp., is a botanical that is widely used in the nutraceutical sector to control cholesterol and blood glucose levels. It is also a molecule that is effective in limiting diarrhea due to its multi-factorial properties, including its antimicrobial, gut eubiotic and antisecretive actions, and its ability to slow gut motility. In our routine clinical practice, we have suggested the use of a berberine-based nutraceutical, formulated with melatonin and depolymerized guar gum, to patients affected by functional diarrhea (FD) or by diarrhea-type irritable bowel syndrome (IBS-D). METHODS We have therefore retrospectively analyzed the clinical effect of such a nutritional supplement in these two sub-groups of patients. RESULTS Despite the highly pragmatic scheme of our study, our findings strongly confirm the antidiarrheal properties of berberine and recommend its use in some gut functional diseases characterized by frequent evacuation of mushy and/or watery stools. In fact, even after 30 days of treatment, the berberine-based nutritional supplement significantly reduces diarrheal events by 50-70%. After 90 days, this reduction improves to between 70 and 80%, with a reduction of more than 60% in the number of evacuations per week and with more than 50% of treated subjects demonstrating normalized, according to self-reported Bristol Stool Scale categorization, stool consistency. The product is well tolerated and adherence to the proposed therapy is good. Common side effects of the product are flatulence and meteorism, likely due to the "acarbose-like" berberine effects on gut α-glucosidase. CONCLUSIONS Patients, especially those preferring "natural" therapy, can be successfully treated, when affected by a gut functional disease characterized by diarrhea, by berberine-based products.

[1]  J. Keller,et al.  [Chronic diarrhoea in daily practice; article for education and training purposes]. , 2019, Nederlands tijdschrift voor geneeskunde.

[2]  Ming Yang,et al.  A Novel Method to Mask the Bitter Taste of Berberine Hydrochloride: Powder Surface Modification , 2018, Pharmacognosy magazine.

[3]  J. Tack,et al.  Existing and emerging therapies for managing constipation and diarrhea. , 2017, Current opinion in pharmacology.

[4]  W. Whitehead,et al.  Update on Rome IV Criteria for Colorectal Disorders: Implications for Clinical Practice , 2017, Current Gastroenterology Reports.

[5]  R. Carson,et al.  Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea , 2017, Health and Quality of Life Outcomes.

[6]  J. Slavin,et al.  In vitro analysis of partially hydrolyzed guar gum fermentation on identified gut microbiota. , 2016, Anaerobe.

[7]  H. Hosseinzadeh,et al.  Berberis Vulgaris and Berberine: An Update Review , 2016, Phytotherapy research : PTR.

[8]  Brian P. Meier,et al.  The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference , 2016, Medical decision making : an international journal of the Society for Medical Decision Making.

[9]  Hyungwoo Kim,et al.  Berberine induces pacemaker potential inhibition via cGMP-dependent ATP-sensitive K+ channels by stimulating mu/delta opioid receptors in cultured interstitial cells of Cajal from mouse small intestine. , 2016, Molecular medicine reports.

[10]  K. Whelan,et al.  Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea‐predominant irritable bowel syndrome , 2016, Alimentary pharmacology & therapeutics.

[11]  Q. Pan,et al.  Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner , 2015, PloS one.

[12]  Q. Pan,et al.  A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea‐Predominant Irritable Bowel Syndrome , 2015, Phytotherapy research : PTR.

[13]  Weihua Liu,et al.  Berberine Blocks the Relapse of Clostridium difficile Infection in C57BL/6 Mice after Standard Vancomycin Treatment , 2015, Antimicrobial Agents and Chemotherapy.

[14]  Ruben Abagyan,et al.  Rational Design of Berberine-Based FtsZ Inhibitors with Broad-Spectrum Antibacterial Activity , 2014, PloS one.

[15]  K. Ho,et al.  Melatonin for the treatment of irritable bowel syndrome. , 2014, World journal of gastroenterology.

[16]  H. Cai,et al.  Inhibiting Roles of Berberine in Gut Movement of Rodents are Related to Activation of the Endogenous Opioid System , 2013, Phytotherapy research : PTR.

[17]  N. Talley,et al.  Sa1105 International Perceptions of IBS: Survey of IBS Investigators From the Global Multinational IBS Initiative , 2013 .

[18]  P. Moayyedi,et al.  Peripheral mechanisms in irritable bowel syndrome. , 2013, The New England journal of medicine.

[19]  Xin Wang,et al.  Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model. , 2012, Fitoterapia.

[20]  G. Marchesini,et al.  Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[21]  E. K. Kemsley,et al.  Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota , 2010, BMC gastroenterology.

[22]  L. Good,et al.  Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine , 2010, PloS one.

[23]  Jie-shou Li,et al.  The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells. , 2009, Fitoterapia.

[24]  Shousi Lu,et al.  Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats. , 2008, Die Pharmazie.

[25]  H. Shi,et al.  Palmatine, a protoberberine alkaloid, inhibits both Ca2+‐ and cAMP‐activated Cl− secretion in isolated rat distal colon , 2008, British journal of pharmacology.

[26]  K. Moji,et al.  Suppressive effect of partially hydrolyzed guar gum on transitory diarrhea induced by ingestion of maltitol and lactitol in healthy humans , 2007, European Journal of Clinical Nutrition.

[27]  E. Giannini,et al.  Role of partially hydrolyzed guar gum in the treatment of irritable bowel syndrome. , 2006, Nutrition.

[28]  K. Gwee,et al.  Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double‐blind placebo‐controlled study , 2005, Alimentary pharmacology & therapeutics.

[29]  D. Drossman,et al.  The functional gastrointestinal disorders and the Rome III process. , 1999, Gastroenterology.

[30]  A. Baird,et al.  Berberine inhibits ion transport in human colonic epithelia. , 1999, European journal of pharmacology.

[31]  Rabbani Gh.  Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins. , 1996 .

[32]  J. Yuan,et al.  [Effect of berberine on transit time of human small intestine]. , 1994, Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine.

[33]  H. Homann,et al.  Reduction in diarrhea incidence by soluble fiber in patients receiving total or supplemental enteral nutrition. , 1994, JPEN. Journal of parenteral and enteral nutrition.

[34]  C. Sninsky,et al.  Effect of berberine on myoelectric activity and transit of the small intestine in rats. , 1989, Gastroenterology.

[35]  E. Beachey,et al.  Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli , 1988, Antimicrobial Agents and Chemotherapy.

[36]  T. Butler,et al.  Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. , 1987, The Journal of infectious diseases.

[37]  Khin-Maung-U,et al.  Clinical trial of berberine in acute watery diarrhoea. , 1985, British medical journal.

[38]  T. Subbaiah,et al.  Effect of Berberine Sulphate on Entamoeba histolytica , 1967, Nature.

[39]  P. Gray,et al.  Assimilation of Berberine by Bacteria , 1956, Nature.

[40]  Tao-Tao Liu,et al.  Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe-/- mice. , 2018, Atherosclerosis.

[41]  A. Cicero,et al.  Berberine and Its Role in Chronic Disease. , 2016, Advances in experimental medicine and biology.

[42]  G. Rabbani.  Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins. , 1996, Danish medical bulletin.