Effect of probiotics on obesity-related markers per enterotype: a double-blind, placebo-controlled, randomized clinical trial



Prevention and improvement of disease symptoms are important issues, and probiotics are suggested as a good treatment for controlling the obesity. Human gut microbiota has different community structures. Because gut microbial composition is assumed to be linked to probiotic function, this study evaluated the efficacy of probiotics on obesity-related clinical markers according to gut microbial enterotype.


Fifty subjects with body mass index over 25 kg/m2 were randomly assigned to either the probiotic or placebo group. Each group received either unlabeled placebo or probiotic capsules for 12 weeks. Body weight, waist circumference, and body composition were measured every 3 weeks. Using computed tomography, total abdominal fat area and visceral fat area were measured. Blood and fecal samples were collected before and after the intervention for biochemical parameters and gut microbial compositions analysis.


Gut microbial compositions of all the subjects were classified into two enterotypes according to Prevotella/Bacteroides ratio. The fat percentage, blood glucose, and insulin significantly increased in the Prevotella-rich enterotype of the placebo group. The obesity-related markers, such as waist circumference, total fat area, visceral fat, and ratio of visceral to subcutaneous fat area, were significantly reduced in the probiotic group. The decrease of obesity-related markers was greater in the Prevotella-rich enterotype than in the Bacteroides-rich enterotype.


Administration of probiotics improved obesity-related markers in obese people, and the efficacy of probiotics differed per gut microbial enterotype and greater responses were observed in the Prevotella-dominant enterotype.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Agha M, Agha R. The rising prevalence of obesity: part A: impact on public health. Int J Surg Oncol (N Y). 2017;2(7):e17. https://doi.org/10.1097/IJ9.0000000000000017.

    Article  Google Scholar 

  2. 2.

    Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444(7121):875–80. https://doi.org/10.1038/nature05487.

    CAS  Article  Google Scholar 

  3. 3.

    Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17(9):961–9.

    CAS  Article  Google Scholar 

  4. 4.

    Global BMIMC, Di Angelantonio E, Bhupathiraju S, Wormser D, Gao P, Kaptoge S, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388(10046):776–86. https://doi.org/10.1016/S0140-6736(16)30175-1.

    Article  Google Scholar 

  5. 5.

    Anandacoomarasamy A, Fransen M, March L. Obesity and the musculoskeletal system. Curr Opin Rheumatol. 2009;21(1):71–7. https://doi.org/10.1097/bor.0b013e32831bc0d7.

    Article  PubMed  Google Scholar 

  6. 6.

    Harris R, Card TR, Delahooke T, Aithal GP, Guha IN. Obesity is the most common risk factor for chronic liver disease: results from a risk stratification pathway using transient elastography. Am J Gastroenterol. 2019;114(11):1744–52. https://doi.org/10.14309/ajg.0000000000000357.

    Article  PubMed  Google Scholar 

  7. 7.

    Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014;28(4):637–53. https://doi.org/10.1016/j.bpg.2014.07.008.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Castro AM. Macedo-de la concha LE, Pantoja-Meléndez CA. Low-grade inflammation and its relation to obesity and chronic degenerative diseases. Revista Médica del Hospital General de México. 2017;80(2):101–5. https://doi.org/10.1016/j.hgmx.2016.06.011.

    Article  Google Scholar 

  9. 9.

    Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394(6696):897–901. https://doi.org/10.1038/29795.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Youssef DM, Elbehidy RM, Shokry DM, Elbehidy EM. The influence of leptin on Th1/Th2 balance in obese children with asthma. J Bras Pneumol. 2013;39(5):562–8. https://doi.org/10.1590/S1806-37132013000500006.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Rogero MM, Calder PC. Obesity, inflammation, Toll-like receptor 4 and fatty acids. Nutrients. 2018;10(4):432. https://doi.org/10.3390/nu10040432.

    CAS  Article  PubMed Central  Google Scholar 

  12. 12.

    Galli C, Calder PC. Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review. Ann Nutr Metab. 2009;55(1–3):123–39. https://doi.org/10.1159/000228999.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Simopoulos AP, DiNicolantonio JJ. The importance of a balanced ω-6 to ω-3 ratio in the prevention and management of obesity. Open Heart. 2016;3(2):e000385–e. https://doi.org/10.1136/openhrt-2015-000385.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Roberts CK, Barnard RJ. Effects of exercise and diet on chronic disease. J Appl Physiol (Bethesda, Md : 1985). 2005;98(1):3–30. https://doi.org/10.1152/japplphysiol.00852.2004.

    Article  Google Scholar 

  15. 15.

    Feinberg AP, Irizarry RA, Fradin D, Aryee MJ, Murakami P, Aspelund T, et al. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med. 2010;2(49):49ra67. https://doi.org/10.1126/scitranslmed.3001262.

    Article  Google Scholar 

  16. 16.

    Alonso R, Farías M, Alvarez V, Cuevas A. Chapter 7 - the genetics of obesity. In: Rodriguez-Oquendo A, editor. Translational cardiometabolic genomic medicine. Boston: Academic Press; 2016. p. 161–77.

    Google Scholar 

  17. 17.

    Romieu I, Dossus L, Barquera S, Blottiere HM, Franks PW, Gunter M, et al. Energy balance and obesity: what are the main drivers? Cancer Causes Control : CCC. 2017;28(3):247–58. https://doi.org/10.1007/s10552-017-0869-z.

    Article  Google Scholar 

  18. 18.

    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31. https://doi.org/10.1038/nature05414.

    Article  PubMed  Google Scholar 

  19. 19.

    Turnbaugh PJ, Gordon JI. The core gut microbiome, energy balance and obesity. J Physiol. 2009;587(Pt 17):4153–8. https://doi.org/10.1113/jphysiol.2009.174136.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535:65–74. https://doi.org/10.1038/nature18847.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2008a;457:480. https://doi.org/10.1038/nature07540 https://www.nature.com/articles/nature07540#supplementary-information.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008b;3(4):213–23. https://doi.org/10.1016/j.chom.2008.02.015.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14–6ra. https://doi.org/10.1126/scitranslmed.3000322.

    Article  Google Scholar 

  24. 24.

    Hughes RL, Marco ML, Hughes JP, Keim NL, Kable ME. The role of the gut microbiome in predicting response to diet and the development of precision nutrition models—part I: overview of current methods. Adv Nutr. 2019a;10(6):953–78. https://doi.org/10.1093/advances/nmz022.

    Article  PubMed  Google Scholar 

  25. 25.

    Hughes RL, Kable ME, Marco M, Keim NL. The role of the gut microbiome in predicting response to diet and the development of precision nutrition models. Part II: Results. Adv Nutr. 2019b;10(6):979–98. https://doi.org/10.1093/advances/nmz049.

    Article  Google Scholar 

  26. 26.

    Bubnov R, Babenko L, Lazarenko L, Kryvtsova M, Shcherbakov O, Zholobak N, et al. Can tailored nanoceria act as a prebiotic? Report on improved lipid profile and gut microbiota in obese mice. EPMA J. 2019;10(4):317–35. https://doi.org/10.1007/s13167-019-00190-1.

    Article  Google Scholar 

  27. 27.

    Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and Synbiotics on human health. Nutrients. 2017;9(9):1021. https://doi.org/10.3390/nu9091021.

    CAS  Article  PubMed Central  Google Scholar 

  28. 28.

    Wang L, Guo M-J, Gao Q, Yang J-F, Yang L, Pang X-L, et al. The effects of probiotics on total cholesterol: a meta-analysis of randomized controlled trials. Medicine. 2018;97(5):e9679–e. https://doi.org/10.1097/MD.0000000000009679.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Collado MC, Meriluoto J, Salminen S. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett Appl Microbiol. 2007;45(4):454–60. https://doi.org/10.1111/j.1472-765X.2007.02212.x.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–14. https://doi.org/10.1038/nrgastro.2014.66.

    Article  PubMed  Google Scholar 

  31. 31.

    Bubnov RV, Babenko LP, Lazarenko LM, Mokrozub VV, Demchenko OA, Nechypurenko OV, et al. Comparative study of probiotic effects of Lactobacillus and Bifidobacteria strains on cholesterol levels, liver morphology and the gut microbiota in obese mice. EPMA J. 2017;8(4):357–76. https://doi.org/10.1007/s13167-017-0117-3.

    Article  Google Scholar 

  32. 32.

    Park D-Y, Ahn Y-T, Park S-H, Huh C-S, Yoo S-R, Yu R, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One. 2013;8(3):e59470. https://doi.org/10.1371/journal.pone.0059470.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Huang Y, Wang J, Quan G, Wang X, Yang L, Zhong L. <span class="named-content genus-species" id="named-content-1">Lactobacillus acidophilus</span> ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein e-knockout mice. Appl Environ Microbiol. 2014;80(24):7496. https://doi.org/10.1128/AEM.02926-14.

    Article  Google Scholar 

  34. 34.

    Aronsson L, Huang Y, Parini P, Korach-André M, Håkansson J, Gustafsson J-Å, et al. Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4). PLoS One. 2010;5(9):e13087. https://doi.org/10.1371/journal.pone.0013087.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol. 2008;49(5):821–30. https://doi.org/10.1016/j.jhep.2008.05.025.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Hidalgo-Cantabrana C, Delgado S, Ruiz L, Ruas-Madiedo P, Sánchez B, Margolles A. Bifidobacteria and their health-promoting effects. Microbiol Spectr. 2017;5(3). https://doi.org/10.1128/microbiolspec.BAD-0010-2016.

  37. 37.

    Thomson P, Medina DA, Garrido D. Human milk oligosaccharides and infant gut bifidobacteria: molecular strategies for their utilization. Food Microbiol. 2018;75:37–46. https://doi.org/10.1016/j.fm.2017.09.001.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Ruiz L, Delgado S, Ruas-Madiedo P, Sánchez B, Margolles A. Bifidobacteria and their molecular communication with the immune system. Front Microbiol. 2017;8:2345. https://doi.org/10.3389/fmicb.2017.02345.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–7. https://doi.org/10.1038/nature11053.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Moschen AR, Wieser V, Tilg H. Dietary factors: major regulators of the gut’s microbiota. Gut Liver. 2012;6(4):411–6. https://doi.org/10.5009/gnl.2012.6.4.411.

    CAS  Article  Google Scholar 

  41. 41.

    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8. https://doi.org/10.1126/science.1208344.

    CAS  Article  Google Scholar 

  42. 42.

    Lim MY, Rho M, Song Y-M, Lee K, Sung J, Ko G. Stability of gut enterotypes in Korean monozygotic twins and their association with biomarkers and diet. Sci Rep. 2014;4:7348. https://doi.org/10.1038/srep07348 https://www.nature.com/articles/srep07348#supplementary-information.

  43. 43.

    Liang C, Tseng H-C, Chen H-M, Wang W-C, Chiu C-M, Chang J-Y, et al. Diversity and enterotype in gut bacterial community of adults in Taiwan. BMC Genomics. 2017;18(1):932. https://doi.org/10.1186/s12864-016-3261-6.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80. https://doi.org/10.1038/nature09944.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    de Moraes AC, Fernandes GR, da Silva IT, Almeida-Pititto B, Gomes EP, Pereira AD, et al. Enterotype may drive the dietary-associated cardiometabolic risk factors. Front Cell Infect Microbiol. 2017;7:47. https://doi.org/10.3389/fcimb.2017.00047.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahl MI. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet. Appl Environ Microbiol. 2014;80(3):1142–9. https://doi.org/10.1128/aem.03549-13.

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Hjorth MF, Roager HM, Larsen TM, Poulsen SK, Licht TR, Bahl MI, et al. Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. Int J Obes. 2017;42:580–3. https://doi.org/10.1038/ijo.2017.220.

    Article  Google Scholar 

  48. 48.

    Hjorth MF, Blaedel T, Bendtsen LQ, Lorenzen JK, Holm JB, Kiilerich P, et al. Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis. Int J Obes (Lond). 2019;43(1):149–57. https://doi.org/10.1038/s41366-018-0093-2.

    Article  Google Scholar 

  49. 49.

    Organization WH. The Asia-Pacific perspective: redefining obesity and its treatment. Sydney: Health Communications Australia; 2000.

  50. 50.

    Organization WH. Waist circumference and waist-hip ratio: report of a WHO expert consultation, Geneva, 8-11 December 2008. 2011.

  51. 51.

    Perry AC, Applegate EB, Jackson ML, Deprima S, Goldberg RB, Ross R, et al. Racial differences in visceral adipose tissue but not anthropometric markers of health-related variables. J Appl Physiol (Bethesda, Md : 1985). 2000;89(2):636–43. https://doi.org/10.1152/jappl.2000.89.2.636.

    CAS  Article  Google Scholar 

  52. 52.

    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.

    CAS  Article  Google Scholar 

  53. 53.

    Lim MY, Song E-J, Kim SH, Lee J, Nam Y-D. Comparison of DNA extraction methods for human gut microbial community profiling. Syst Appl Microbiol. 2018;41(2):151–7. https://doi.org/10.1016/j.syapm.2017.11.008.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20. https://doi.org/10.1093/bioinformatics/btu170.

    CAS  Article  Google Scholar 

  55. 55.

    Zhang J, Kobert K, Flouri T, Stamatakis A. PEAR: a fast and accurate Illumina Paired-End reAd mergeR. Bioinformatics. 2014;30(5):614–20. https://doi.org/10.1093/bioinformatics/btt593.

    Article  Google Scholar 

  56. 56.

    Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27(16):2194–200. https://doi.org/10.1093/bioinformatics/btr381.

    CAS  Article  Google Scholar 

  57. 57.

    Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet C, Al-Ghalith GA, et al. QIIME 2: reproducible, interactive, scalable, and extensible microbiome data science. Peer J Preprints. 2018;6:e27295v2. https://doi.org/10.7287/peerj.preprints.27295v2.

  58. 58.

    Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med. 2002;162(18):2074–9.

    Article  Google Scholar 

  59. 59.

    Janssen I, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health risk. Am J Clin Nutr. 2004;79(3):379–84.

    CAS  Article  Google Scholar 

  60. 60.

    Jung SP, Lee KM, Kang JH, Yun SI, Park HO, Moon Y, et al. Effect of Lactobacillus gasseri BNR17 on overweight and obese adults: a randomized, double-blind clinical trial. Korean J Fam Med. 2013;34(2):80–9. https://doi.org/10.4082/kjfm.2013.34.2.80.

    Article  Google Scholar 

  61. 61.

    Matsuzawa Y, Nakamura T, Shimomura I, Kotani K. Visceral fat accumulation and cardiovascular disease. Obes Res. 1995;3(Suppl 5):645s–7s.

    Article  Google Scholar 

  62. 62.

    Despres JP. Cardiovascular disease under the influence of excess visceral fat. Crit Pathw Cardiol. 2007;6(2):51–9. https://doi.org/10.1097/HPC.0b013e318057d4c9.

  63. 63.

    Fukuda T, Bouchi R. Ratio of visceral-to-subcutaneous fat area predicts cardiovascular events in patients with type 2 diabetes. J Diabetes Investig.  2018;9:396-402. https://doi.org/10.1111/jdi.12713.

    Article  Google Scholar 

  64. 64.

    Kaess BM, Pedley A, Massaro JM, Murabito J, Hoffmann U, Fox CS. The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk. Diabetologia. 2012;55(10):2622–30. https://doi.org/10.1007/s00125-012-2639-5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Barreto FM, Colado Simão AN, Morimoto HK, Batisti Lozovoy MA, Dichi I, Helena da Silva Miglioranza L. Beneficial effects of Lactobacillus plantarum on glycemia and homocysteine levels in postmenopausal women with metabolic syndrome. Nutrition 2014;30(7):939–942. doi:https://doi.org/10.1016/j.nut.2013.12.004.

    CAS  Article  Google Scholar 

  66. 66.

    Takemura N, Okubo T, Sonoyama K. Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Exp Biol Med (Maywood, NJ). 2010;235(7):849–56. https://doi.org/10.1258/ebm.2010.009377.

    CAS  Article  Google Scholar 

  67. 67.

    Takahashi S, Anzawa D, Takami K, Ishizuka A, Mawatari T, Kamikado K, et al. Effect of Bifidobacterium animalis ssp. lactis GCL2505 on visceral fat accumulation in healthy Japanese adults: a randomized controlled trial. Biosci Microbiota Food Health. 2016;35(4):163–71. https://doi.org/10.12938/bmfh.2016-002.

  68. 68.

    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(6):636–43. https://doi.org/10.1038/ejcn.2010.19.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Kortman GAM, Raffatellu M, Swinkels DW, Tjalsma H. Nutritional iron turned inside out: intestinal stress from a gut microbial perspective. FEMS Microbiol Rev. 2014;38(6):1202–34. https://doi.org/10.1111/1574-6976.12086.

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Das NK, Schwartz AJ, Barthel G, Inohara N, Liu Q, Sankar A, et al. Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metabolism. 2019;S1550–4131(19):30560–1. https://doi.org/10.1016/j.cmet.2019.10.005.

    CAS  Article  Google Scholar 

  71. 71.

    Skrypnik K, Suliburska J. Association between the gut microbiota and mineral metabolism. J Sci Food Agric. 2018;98(7):2449–60. https://doi.org/10.1002/jsfa.8724.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Raimondi S, Amaretti A, Leonardi A, Quartieri A, Gozzoli C, Rossi M. Conjugated linoleic acid production by Bifidobacteria: screening, kinetic, and composition. Biomed Res Int. 2016;2016:8654317. https://doi.org/10.1155/2016/8654317.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Kim JH, Kim Y, Kim YJ, Park Y. Conjugated linoleic acid: potential health benefits as a functional food ingredient. Annu Rev Food Sci Technol. 2016a;7:221–44. https://doi.org/10.1146/annurev-food-041715-033028.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Patterson E, Wall R, Lisai S, Ross RP, Dinan TG, Cryan JF, et al. Bifidobacterium breve with α-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat. Sci Rep. 2017;7:43300. https://doi.org/10.1038/srep43300 https://www.nature.com/articles/srep43300#supplementary-information.

    Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Kondo S, Kamei A, Xiao JZ, Iwatsuki K, Abe K. Bifidobacterium breve B-3 exerts metabolic syndrome-suppressing effects in the liver of diet-induced obese mice: a DNA microarray analysis. Benefic Microbes. 2013;4(3):247–51. https://doi.org/10.3920/BM2012.0019.

    CAS  Article  Google Scholar 

  76. 76.

    Kondo S, Xiao J-z, Satoh T, Odamaki T, Takahashi S, Sugahara H, et al. Antiobesity effects of Bifidobacterium breve strain B-3 supplementation in a mouse model with high-fat diet-induced obesity. Biosci Biotechnol Biochem. 2010;74(8):1656–61. https://doi.org/10.1271/bbb.100267.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Molly K, Smet ID, Nollet L, Woestyne MV, Verstraete W. Effect of lactobacilli on the ecology of the gastro-intestinal microbiota cultured in the SHIME reactor. Microb Ecol Health Dis. 1996;9(2):79–89. https://doi.org/10.3109/08910609609166446.

    Article  Google Scholar 

  78. 78.

    Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol. 2008;74(16):4985–96. https://doi.org/10.1128/AEM.00753-08.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Wu C-C, Weng W-L, Lai W-L, Tsai H-p, Liu W-H, Lee M-H et al. Effect of Lactobacillus plantarum strain K21 on high-fat diet-fed obese mice. Evid Based Complement Alternat Med. 2015;2015:391767. doi:DOI:https://doi.org/10.1155/2015/391767.

  80. 80.

    Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog. 2012;53(2):100–8. https://doi.org/10.1016/j.micpath.2012.05.007.

    Article  PubMed  Google Scholar 

  81. 81.

    Michael DR, Davies TS, Moss JWE, Calvente DL, Ramji DP, Marchesi JR, et al. The anti-cholesterolaemic effect of a consortium of probiotics: an acute study in C57BL/6J mice. Sci Rep. 2017;7(1):2883. https://doi.org/10.1038/s41598-017-02889-5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Mastromarino P, Macchia S, Meggiorini L, Trinchieri V, Mosca L, Perluigi M, et al. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect. 2009;15(1):67–74. https://doi.org/10.1111/j.1469-0691.2008.02112.x.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Kobyliak N, Conte C, Cammarota G, Haley AP, Styriak I, Gaspar L, et al. Probiotics in prevention and treatment of obesity: a critical view. Nutri Metab. 2016;13:14. https://doi.org/10.1186/s12986-016-0067-0.

    CAS  Article  Google Scholar 

  84. 84.

    Brusaferro A, Cozzali R, Orabona C, Biscarini A, Farinelli E, Cavalli E, et al. Is it time to use probiotics to prevent or treat obesity? Nutrients. 2018;10(11). https://doi.org/10.3390/nu10111613.

    Article  Google Scholar 

  85. 85.

    X-M L, HA L, M K, E-S P, K-Y P. Probiotic effects of Lactobacillus plantarum strains isolated from Kimchi. J Korean Soc Food Sci Nutr. 2016;45(12):1717–24.

    Article  Google Scholar 

  86. 86.

    Kim HW, Hong R, Choi EY, Yu K, Kim N, Hyeon JY, et al. A probiotic mixture regulates T cell balance and reduces atopic dermatitis symptoms in mice. Front Microbiol. 2018a;9(2414). https://doi.org/10.3389/fmicb.2018.02414.

  87. 87.

    Lee SJ, Bose S, Seo J-G, Chung W-S, Lim C-Y, Kim H. The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: a randomized double-blind controlled clinical trial. Clin Nutr. 2014;33(6):973–81. https://doi.org/10.1016/j.clnu.2013.12.006.

    Article  PubMed  Google Scholar 

  88. 88.

    Kwak M-J, Yoon J-K, Kwon S-K, Chung M-J, Seo J-G, Kim JF. Complete genome sequence of the probiotic bacterium Bifidobacterium breve KCTC 12201BP isolated from a healthy infant. J Biotechnol. 2015;214:156–7. https://doi.org/10.1016/j.jbiotec.2015.09.035.

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Shin J-H, Chung M-J, Seo J-G. A multistrain probiotic formulation attenuates skin symptoms of atopic dermatitis in a mouse model through the generation of CD4(+)Foxp3(+) T cells. Food Nutr Res. 2016;60:32550. https://doi.org/10.3402/fnr.v60.32550.

    CAS  Article  PubMed  Google Scholar 

  90. 90.

    Kim MS, Byun JS, Yoon YS, Yum DY, Chung MJ, Lee JC. A probiotic combination attenuates experimental colitis through inhibition of innate cytokine production. Benefic Microbes. 2016b;8(2):231–41. https://doi.org/10.3920/BM2016.0031.

    CAS  Article  Google Scholar 

  91. 91.

    J-S L, M-J C, J-G S. In vitro evaluation of antimicrobial activity of lactic acid bacteria against Clostridium difficile. Toxicological Research. 2013;29(2):99–106.

    Article  Google Scholar 

  92. 92.

    Chung M-J. Efficacy and safety evaluation of anti-obesity probiotics. Unpublished raw data. 2017.

  93. 93.

    Canada Go. Accepted claims about the nature of probiotic microorganisms in food. 2019. http://www.hc-sc.gc.ca/fn-an/label-etiquet/claims-reclam/probiotics_claims-allegations_probiotiques-eng.php%20.

    Google Scholar 

  94. 94.

    Hobbs CA, Saigo K, Koyanagi M, Hayashi S-M. Magnesium stearate, a widely-used food additive, exhibits a lack of in vitro and in vivo genotoxic potential. Toxicol Rep. 2017;4:554–9. https://doi.org/10.1016/j.toxrep.2017.10.003.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491–502. https://doi.org/10.1038/nrgastro.2017.75.

    Article  PubMed  Google Scholar 

  96. 96.

    Reid G, Abrahamsson T, Bailey M, Bindels LB, Bubnov R, Ganguli K, et al. How do probiotics and prebiotics function at distant sites? Benefic Microbes. 2017;8(4):521–33. https://doi.org/10.3920/BM2016.0222.

    CAS  Article  Google Scholar 

  97. 97.

    Andersen CJ, Murphy KE, Fernandez ML. Impact of obesity and metabolic syndrome on immunity. Adv Nutr. 2016;7(1):66–75. https://doi.org/10.3945/an.115.010207.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Cheru L, Saylor CF, Lo J. Gastrointestinal barrier breakdown and adipose tissue inflammation. Curr Obes Rep. 2019;8(2):165–74. https://doi.org/10.1007/s13679-019-00332-6.

    Article  PubMed  Google Scholar 

  99. 99.

    Chang C-C, Sia K-C, Chang J-F, Lin C-M, Yang C-M, Huang K-Y, et al. Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. Int J Med Sci. 2019;16(1):167–79. https://doi.org/10.7150/ijms.24068.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Moss RB, Moll T, El-Kalay M, Kohne C, Soo Hoo W, Encinas J, et al. Th1/Th2 cells in inflammatory disease states: therapeutic implications. Expert Opin Biol Ther. 2004;4(12):1887–96. https://doi.org/10.1517/14712598.4.12.1887.

    CAS  Article  PubMed  Google Scholar 

  101. 101.

    Charlton B, Lafferty KJ. The Th1/Th2 balance in autoimmunity. Curr Opin Immunol. 1995;7(6):793–8. https://doi.org/10.1016/0952-7915(95)80050-6.

    CAS  Article  PubMed  Google Scholar 

  102. 102.

    Mazzarella G, Bianco A, Catena E, De Palma R, Abbate GF. Th1/Th2 lymphocyte polarization in asthma. Allergy. 2000;55(Suppl 61):6–9. https://doi.org/10.1034/j.1398-9995.2000.00511.x.

    Article  PubMed  Google Scholar 

  103. 103.

    Han JM, Levings MK. Immune regulation in obesity-associated adipose inflammation. J Immunol. 2013;191(2):527. https://doi.org/10.4049/jimmunol.1301035.

    CAS  Article  PubMed  Google Scholar 

  104. 104.

    Richardson VR, Smith KA, Carter AM. Adipose tissue inflammation: feeding the development of type 2 diabetes mellitus. Immunobiology. 2013;218(12):1497–504. https://doi.org/10.1016/j.imbio.2013.05.002.

    CAS  Article  PubMed  Google Scholar 

  105. 105.

    Savcheniuk OA, Virchenko OV, Falalyeyeva TM, Beregova TV, Babenko LP, Lazarenko LM, et al. The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention. EPMA J. 2014;5(1):2. https://doi.org/10.1186/1878-5085-5-2.

    Article  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Tymoshok NO, Lazarenko LM, Bubnov RV, Shynkarenko LN, Babenko LP, Mokrozub VV, et al. New aspects the regulation of immune response through balance Th1/Th2 cytokines. EPMA J. 2014;5(1):A134. https://doi.org/10.1186/1878-5085-5-S1-A134.

  107. 107.

    Мokrozub VV, Lazarenko LM, Sichel LM, Babenko LP, Lytvyn PM, Demchenko OM, et al. The role of beneficial bacteria wall elasticity in regulating innate immune response. EPMA J. 2015;6(1):13–5. https://doi.org/10.1186/s13167-015-0035-1.

  108. 108.

    Shockman GD, Barren JF. Structure, function, and assembly of cell walls of gram-positive bacteria. Annu Rev Microbiol 1983;37(1):501–527. doi:https://doi.org/10.1146/annurev.mi.37.100183.002441.

    CAS  Article  Google Scholar 

  109. 109.

    Zeuthen LH, Fink LN, Frøkiær H. Toll-like receptor 2 and nucleotide-binding oligomerization domain-2 play divergent roles in the recognition of gut-derived lactobacilli and bifidobacteria in dendritic cells. Immunology. 2008;124(4):489–502. https://doi.org/10.1111/j.1365-2567.2007.02800.x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M, et al. Safety of probiotics that contain lactobacilli or bifidobacteria. Clin Infect Dis. 2003;36(6):775–80. https://doi.org/10.1086/368080.

    CAS  Article  PubMed  Google Scholar 

  111. 111.

    Boyle RJ, Robins-Browne RM, Tang MLK. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr. 2006;83(6):1256–447. https://doi.org/10.1093/ajcn/83.6.1256.

    CAS  Article  PubMed  Google Scholar 

  112. 112.

    Schork NJ. Personalized medicine: time for one-person trials. Nature. 2015;520(7549):609–11. https://doi.org/10.1038/520609a.

    CAS  Article  PubMed  Google Scholar 

  113. 113.

    Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016;7(1):23. https://doi.org/10.1186/s13167-016-0072-4.

    Article  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Nebert DW, Zhang G, Vesell ES. From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons. Future Directions Drug Metabolism Reviews. 2008;40(2):187–224. https://doi.org/10.1080/03602530801952864.

    CAS  Article  PubMed  Google Scholar 

  115. 115.

    John GK, Wang L, Nanavati J, Twose C, Singh R, Mullin G. Dietary alteration of the gut microbiome and its impact on weight and fat mass: a systematic review and meta-analysis. Genes. 2018;9(3). https://doi.org/10.3390/genes9030167.

    Article  Google Scholar 

  116. 116.

    Park S, Bae J-H. Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res. 2015;35(7):566–75. https://doi.org/10.1016/j.nutres.2015.05.008.

    CAS  Article  PubMed  Google Scholar 

  117. 117.

    Borgeraas H, Johnson LK, Skattebu J, Hertel JK, Hjelmesaeth J. Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2018;19(2):219–32. https://doi.org/10.1111/obr.12626.

    CAS  Article  PubMed  Google Scholar 

  118. 118.

    Korem T, Zeevi D, Zmora N, Weissbrod O, Bar N, Lotan-Pompan M, et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 2017;25(6):1243–53.e5. https://doi.org/10.1016/j.cmet.2017.05.002.

    CAS  Article  PubMed  Google Scholar 

  119. 119.

    Kang C, Zhang Y, Zhu X, Liu K, Wang X, Chen M, et al. Healthy subjects differentially respond to dietary capsaicin correlating with specific gut enterotypes. J Clin Endocrinol Metab. 2016;101(12):4681–9. https://doi.org/10.1210/jc.2016-2786.

    CAS  Article  PubMed  Google Scholar 

  120. 120.

    Christensen L, Roager HM, Astrup A, Hjorth MF. Microbial enterotypes in personalized nutrition and obesity management. Am J Clin Nutr. 2018a;108(4):645–51. https://doi.org/10.1093/ajcn/nqy175.

    Article  PubMed  Google Scholar 

  121. 121.

    Gu Y, Wang X, Li J, Zhang Y, Zhong H, Liu R, et al. Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment. Nat Commun. 2017a;8(1):1785. https://doi.org/10.1038/s41467-017-01682-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Scientific reports. 2017;7(1):2594. https://doi.org/10.1038/s41598-017-02995-4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189–200. https://doi.org/10.1080/19490976.2015.1134082.

    Article  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Kim YA, Keogh JB, Clifton PM. Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutr Res Rev. 2018b;31(1):35–51. https://doi.org/10.1017/S095442241700018X.

    CAS  Article  PubMed  Google Scholar 

  125. 125.

    Zmora N, Zeevi D, Korem T, Segal E, Elinav E. Taking it personally: personalized utilization of the human microbiome in health and disease. Cell Host Microbe. 2016;19(1):12–20. https://doi.org/10.1016/j.chom.2015.12.016.

    CAS  Article  PubMed  Google Scholar 

  126. 126.

    Bubnov RV, Babenko LP, Lazarenko LM, Mokrozub VV, Demchenko OA, Nechypurenko OV, et al. Comparative study of probiotic effects of Lactobacillus and Bifidobacteria strains on cholesterol levels, liver morphology and the gut microbiota in obese mice. EPMA J. 2017;8(4):357–76. https://doi.org/10.1007/s13167-017-0117-3.

    Article  PubMed  PubMed Central  Google Scholar 

  127. 127.

    Bubnov RV, Spivak MY, Lazarenko LM, Bomba A, Boyko NV. Probiotics and immunity: provisional role for personalized diets and disease prevention. EPMA J. 2015b;6(1):14. https://doi.org/10.1186/s13167-015-0036-0.

    Article  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Christensen L, Roager HM, Astrup A, Hjorth MF. Microbial enterotypes in personalized nutrition and obesity management. Am J Clin Nutr. 2018b;108(4):645–51. https://doi.org/10.1093/ajcn/nqy175.

    Article  PubMed  Google Scholar 

  129. 129.

    Costea PI, Hildebrand F, Arumugam M, Bäckhed F, Blaser MJ, Bushman FD, et al. Enterotypes in the landscape of gut microbial community composition. Nat Microbiol. 2018;3(1):8–16. https://doi.org/10.1038/s41564-017-0072-8.

    CAS  Article  PubMed  Google Scholar 

  130. 130.

    Gu Y, Wang X, Li J, Zhang Y, Zhong H, Liu R, et al. Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment. Nat Commun. 2017b;8(1):1785. https://doi.org/10.1038/s41467-017-01682-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  131. 131.

    de la Cuesta-Zuluaga J, Kelley ST, Chen Y, Escobar JS, Mueller NT, Ley RE, et al. Age- and sex-dependent patterns of gut microbial diversity in human adults msystems. 2019;4(4):e00261–19. https://doi.org/10.1128/mSystems.00261-19.

    Article  PubMed  Google Scholar 

  132. 132.

    Zhang Q, Wang Y. Socioeconomic inequality of obesity in the United States: do gender, age, and ethnicity matter? Soc Sci Med. 2004;58(6):1171–80. https://doi.org/10.1016/s0277-9536(03)00288-0.

    Article  PubMed  Google Scholar 

  133. 133.

    Santos-Marcos JA, Rangel-Zuñiga OA, Jimenez-Lucena R, Quintana-Navarro GM, Garcia-Carpintero S, Malagon MM, et al. Influence of gender and menopausal status on gut microbiota. Maturitas. 2018;116:43–53. https://doi.org/10.1016/j.maturitas.2018.07.008.

    Article  PubMed  Google Scholar 

Download references


This research was supported by Main Research Program (E0170601-03) of the Korea Food Research Institute (KFRI) funded by the Ministry of Science and ICT.

Author information



Corresponding authors

Correspondence to Hojun Kim or Young-Do Nam.

Ethics declarations

Ethical approval

This study was conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. The study protocol was approved by the Institutional Review Board of Ilsan Dongguk University Hospital (approval number 2016-02) and registered in Clinical Research Information Service (CRIS identifier: KCT0002292). Written informed consent has also been obtained from all the participants.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Song, EJ., Han, K., Lim, TJ. et al. Effect of probiotics on obesity-related markers per enterotype: a double-blind, placebo-controlled, randomized clinical trial. EPMA Journal 11, 31–51 (2020). https://doi.org/10.1007/s13167-020-00198-y

Download citation


  • Predictive preventive personalized medicine
  • Probiotics
  • Obesity
  • Clinical trial
  • Gut microbial enterotype