Probiotics for type 2 diabetes mellitus: an anti-diabetic intervention to see beyond the gut

Made Lady Adelaida Purwanta , Ni Putu Ayu Pande Arista Dewi, Made Ratna Saraswati

Made Lady Adelaida Purwanta
Medical Student, Medical Faculty of Udayana University, Faculty of Medicine Udayana University/Sanglah Hospital. Email:

Ni Putu Ayu Pande Arista Dewi
Medical Student, Medical Faculty of Udayana University, Faculty of Medicine Udayana University/Sanglah Hospital

Made Ratna Saraswati
Endocrinology and Metabolism Division, Department of Internal Medicine, Faculty of Medicine Udayana University/Sanglah Hospital
Online First: July 02, 2017 | Cite this Article
Purwanta, M., Dewi, N., Saraswati, M. 2017. Probiotics for type 2 diabetes mellitus: an anti-diabetic intervention to see beyond the gut. Indonesia Journal of Biomedical Science 11(2): 11-18. DOI:10.15562/ijbs.v11i2.139

The increasing cases of type 2 diabetes mellitus (T2DM) have made it a very concerning metabolic disease worldwide. The increasing understanding of the role of gut microbiota in metabolism process has lead to a promising intervention of T2DM that can relieve not only the symptoms but also help improve the disrupted metabolic mechanisms. Probiotics are now widely studied for its potential in the management of T2DM. From 50 journals reviewed, 43 were found suitable as references for this paper. The keywords used are “probiotics,” “gut microbiota,” “obesity” and “type 2 diabetes mellitus” on selected search engines. In general, it has shown that probiotics do have systemic therapeutic effects as it can increase the secretion of gut hormones, maintain gut barrier function and improve inflammatory response, thereby providing a hopeful future for a comprehensive management of metabolic disorders, especially T2DM.

References Diabetes type 2. 2015. (Updated 2015; cited 12th of August 2016, 11:55 AM) Available at:

RISKESDAS. Badan Penelitian dan Pengembangan Kesehatan Kementrian Kesehatan RI. 2013; 89

IDF. Prevention of Diabetes. International Diabetes Federation. 2014. (Cited 13th of August 2016, 12.:15 PM) Available at:

Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 2011; 154: 602-613.

Caricilli AM, Saad MJ a. The role of gut microbiota on insulin resistance. Nutrients. 2013;5(3):829-851. doi:10.3390/nu5030829.

Delzenne NM, Cani PD. Gut microbiota and the pathogenesis of insulin resistance. Curr Diab Rep. 2011;11(3):154-159. doi:10.1007/s11892-011-0191-1.

Cani PD, Everard A, Duparc T. Gut microbiota, enteroendocrine functions and metabolism. Curr Opin Pharmacol. 2013;13(6):935-940. doi: 10.1016/j.coph.2013.09.008.

Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M et al.: Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A 2008, 105:16767-16772.

Backhed F, Ding H, Wang T, Hooper L V, Koh GY, Nagy A, Semenkovich CF, et al. The gut microbiota as an environmental factor that regulates fat storage. PNAS 2004;101(44).

Kaji I, Karaki S, Tanaka R, Kuwahara A: Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1- producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructo- oligosaccharide. J Mol Histol 2011, 42:27-38.

Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G et al.: Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE 2012, 7:e35240.

Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM: Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G protein-coupled receptor FFAR2. Diabetes 2012, 61:364-371.

Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M et al.: TGR5- mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009, 10:167-177.

Ma K, Saha PK, Chan L, Moore DD: Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 2006, 116:1102-1109.

Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI: Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005, 102:11070-11075.

Turnbaugh, P.J.; Hamady, M.; Yatsunenko, T.; Cantarel, B.L.; Duncan, A.; Ley, R.E.; Sogin, M.L.; Jones, W.J.; Roe, B.A.; Affourtit, J.P.; et al. A core gut microbiome in obese and lean twins. Nature 2009, 457, 480–484.

Moreno-Indias I, Cardona F, Tinahones FJ, Queipo-Ortu??o MI. Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus. Front Microbiol. 2014;5(APR):1-10. doi:10.3389/fmicb.2014.00190.

Gut Microbiota Health. Gut microbiota & diabetes. 2016.

Besten Gijs den, Karen van Eunen, Albert K.Groen, Koen Venema. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.The Journal of Lipid reasearh. 2013 Sep;54(9): 2325-2340.doi: 10.1194/jlr. R036012

Yadav H, Lee J-H, Lloyd J, Walter P, Rane SG. Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion. The Journal of Biological Chemistry. 2013;288(35):25088-25097. doi:10.1074/jbc.M113.452516.

Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, et al. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr 2010; 64:636-43.

Kadooka Y, Ogawa A, Ikuyama K, Akai Y, Sato M. The probiotic Lactobacillus gasseri SBT2055 inhibits enlargement of visceral adipocytes and upregulation of serum soluble adhesion molecule (sICAM-1) in rats. Int Dairy J 2011; 30:1-5.

Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, et al. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 2006; 1761:736-44.

Hansen KB, Rosenkilde MM, Knop FK, Wellner N, Diep TA, Rehfeld JF, Andersen UB, Holst JJ, Hansen HS: 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab 2011, 96: E1409-E1417.

Santacruz A, Collado MC, Garcia-Valdes L, Segura MT, Martin- Lagos JA, Anjos T, Marti-Romero M, Lopez RM, Florido J, Campoy C et al.: Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr 2010, 104:83-92.

Reimer RA, McBurney MI. Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon- like peptide-1 and insulin in rats. Endocrinology 1996; 137:3948-56

Gomes AC, Bueno AA, Graziany R, Souza M De, Mota JF. Gut microbiota, probiotics and diabetes. 2014. doi:10.1186/1475-2891-13-60.

Wang J, Tang H, Zhang C, et al. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J. 2015;9(1):1-15. doi:10.1038/ismej.2014.99.

MS Alokail, Sabico S, Al-Saleh Y,Al-Daghri NM, Alkharfy KM. Effects of probiotics in patients with diabetes mellitus type 2: study protocol for randomized, double blind,placebo-controlled trial.2013 Jul 4;14:195.doi:10.1186/1745-6215-14-195.

Mohamadshahi M, Veissi M, Haidari F, Shahbazian H, Kaydani GA, Mohammadi F. Effects of probiotic yogurt consumption on inflammatory biomarkers in patients with type 2 diabetes. BioImpacts. 2014;4(2):83-88. doi:10.5681/bi.2014.007.

Scott KP, Antoine J-M, Midtvedt T, van Hemert S. Manipulating the gut microbiota to maintain health and treat disease. Microbial Ecology in Health and Disease. 2015; 26:10.3402/mehd. v26.25877. doi:10.3402/mehd. v26.25877.

Ianiro G., Bibbò S., Gasbarrini A., Cammarota G. Fecal Microbiota Transplantation for the Management of Digestive and Extradigestive Diseases. CellR4 2014; 2 (6): e1284.

Grover S, Rokana N, Panwar H, Mallappa R, Duary R, Batish V. Management of metabolic syndrome through probiotic and prebiotic interventions. Indian J Endocrinol Metab. 2012;16(1):20-27. doi:10.4103/2230-8210.91178. Bariatric surgery: postoperative concerns. 2008 (Cited 12th of August 2016, 12:01 AM) Available at: Who is a candidate for bariatric surgery? 2016. (Cited 12th of August 2016, 11:58 AM) Available at:

Holzapfel, W.H. & Schillinger, U., 2002. Introduction to pre- and probiotics. Food Research International 35, 109-116.

Siuta-Cruce, P. & Goulet, J., 2001. Improving probiotic microorganisms in food systems. Food Technology 55, 36-42.

Hansen, L.T., Allan-Wojtas, P.M., Jin, Y.–L. & Paulson, A.T., 2002. Survival of Ca-alginate microencapsulated Bifidobacterium spp. in milk and simulated gastrointestinal conditions. Food Microbiology 19, 35-45.

Krasaekoopt W., Bhandari B., Deeth H., 2003. Evaluation of encapsulation techniques of probiotics for yogurt. International Dairy Journal, 13, 3-13.

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