Journal of the Korean Applied Science and Technology (한국응용과학기술학회지)

The Korean Society of Applied Science and Technology (한국응용과학기술학회)
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Effects of 8 weeks Pregnancy Pilates Exercise and Probiotics Combined Treatment on Postnatal Women's Gut-microbiota, Body Composition, Blood Lipids, Obesity Hormones, Inflammatory Indicators

8주간의 출산 전 필라테스 운동과 프로바이오틱스 섭취가 출산 후 여성의 장내미생물, 신체구성, 혈중지질, 비만호르몬, 염증성 사이토카인에 미치는 영향

  • Hyun, Hyun-Ah (Exercise biochemistry Laboratory, Korea National Sport University) ;
  • Choi, Dong-Hun (Exercise biochemistry Laboratory, Korea National Sport University) ;
  • Eom, Hyun-Seoub (Department of Sports Medicine, Konyang University) ;
  • Kim, Ji-Sun (3Department of Sport Industry Major, Jungwon University) ;
  • Oh, Eun-Tak (Department of Sports Science & Rehabilitation, Woosong University) ;
  • Cho, Joon-Yong (Department of Health and Exercise Science, Korea National Sport University)
  • 현아현 (한국체육대학교 운동생화학연구실) ;
  • 최동훈 (한국체육대학교 운동생화학연구실) ;
  • 엄현섭 (건양대학교 스포츠의학과) ;
  • 김지선 (중원대학교 스포츠산업학과) ;
  • 오은택 (우송대학교 스포츠건강재활학과) ;
  • 조준용 (한국체육대학교 운동건강관리학과)
  • Received : 2020.07.28
  • Accepted : 2020.08.26
  • Published : 2020.08.31
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Abstract

The purpose of this study is to explore the effects of pregnant women's taking of probiotics and pilates exercise on Postnatal women's body composition, gut-microbiota, obesity hormones, blood lipid, inflammatory cytokine. Overall clinical trial procedures are as follows. First, a total of 15 pregnant women were classified into 3 groups, probiotics intake+exercise group(PEX, n=5), exercise group(EX, n=5), and control group(CON, n=5). The PEX and EX groups participated in the pilates exercise twice a week for eight weeks, with 10 min for warm-up, 30 min for main exercise and 10 min for cool-dawn. The probiotics had to take one capsule a day on its empty stomach every day. The results showed that intestinal harmful bacteria were inhibited after childbirth in PEX group, and body fat, WHR reduction. There were also positive effects on the decrease of leptin hormone in PEX group and on IL-6, TNF-a levels. The caesarean section ratio of CON group compared to PEX and EX group was found to be high. Conclusion pregnant women's probiotics intake and pilates exercise will be effective in women's abdominal fat reduction after childbirth, and will have positive effects on inflammatory levels and appetite control hormones, which will be effective in preventing and treating obesity for after childbirth.

본 연구의 목적은 출산 전 필라테스 운동과 프로바이오틱스 섭취가 출산 후 여성의 장내미생물, 신체구성, 혈중지질, 비만호르몬, 염증성 사이토카인에 미치는 영향을 알아보는데 있다. 총 15명의 임산부를 운동+프로바이오틱스섭취군(PEX, n=5), 운동군(EX, n=5), 대조군(CON, n=5)으로 구분하였다. PEX 집단과 EX 집단은 8주 동안 주 2회 필라테스 운동에 참여하였고 준비운동 10분, 본 운동 30분, 정리운동 10분으로 실시하였으며, PEX 집단은 매일 공복에 프로바이오틱스 1 캡슐을 섭취하였다. 그 결과 출산 후 PEX 집단의 체지방 및 WHR 수치가 감소하였다. 장내미생물의 변화는 비피도박테리움, 락토바실러스, 클로스트리디움, 퍼미큐테스, 박테리오데스의 구성 수준에서 집단 간 유의한 차이가 나타나지 않았다. 비만 호르몬과 염증성 사이토카인의 변화는 PEX 집단에서 사후 렙틴, IL-6, TNF-a 수치가 감소하는 것으로 나타났고, 혈중 지질 수준에서는 차이가 없었다. 결론적으로 출산 전 필라테스와 프로바이오틱스 병행 처치는 출산 후 여성의 복부지방 감소에 효과적이며 염증 및 비만 관련 호르몬에 긍정적인 영향을 주어 산후 빠른 회복에 도움이 될 것이다.

Keywords

References

  1. H. Ashton, M. Malwina, Naghibi, G. Davinder, "The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome", Foods, Vol. 7, No. 2, pp. 13, (2018). https://doi.org/10.3390/foods7020013
  2. D. Porras, E. Nistal, S. Martinez, J. Gonzalez, M. Garcia, C. Sanche, "Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease", Frontiers in Psychology. Vol. 18, No. 9, pp. 1813, (2018).
  3. M. Elaheh, D. Ali, "The Role of Probiotics in Cancer Treatment: Emphasis on their In Vivo and In Vitro Anti-metastatic Effects", International Journal of Molecular and Cellular Medicine, Vol. 6, No. 2, pp. 66-76, (2017).
  4. M. Wouw, M. Boehme, J.M. Lyte, N. Wiley, C. Strain, O. O'Sullivan, G. Clarke, C. Stanton, T.G. Dinan, J.F. Cryan, "Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations", Journal of Physiology, Vol. 596, No. 20, pp. 4923-4944, (2018). https://doi.org/10.1113/JP276431
  5. A. Clark, N. Mach, "Exercise induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes", Journal of the International Society of Sports Nutrition, Vol. 24, No. 13, pp. 43, (2016). https://doi.org/10.1186/s12970-016-0155-6
  6. E. Nova, H. Perez, M. Gomez, A. Marcos, "The Role of Probiotics on the Microbiota: Effect on Obesity", Nutrition in Clinical Practice, Vol. 31, No. 3, pp. 387-400, (2016). https://doi.org/10.1177/0884533615620350
  7. A. Federico, M. Dallio, S. DI, V. Giorgio, L. Miele, "Gut microbiota, obesity and metabolic disorders", Minerva Gastroenterol Dietol, Vol. 63, No. 4, pp. 337-344, (2017).
  8. A. Renata, Bagarollia, T. Natalia, "Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice", The Journal of Nutritional Biochemistry, Vol. 50, pp. 16-25, (2017). https://doi.org/10.1016/j.jnutbio.2017.08.006
  9. K. Nazarii, A. Ludovico, M. Galyna, K. Liudmyla, B. Luigi, K. Dmytro, D. Oleg, "A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial", Journal of Gastrointestinal and Liver Diseases, Vol. 27, No. 1, pp. 41-49, (2018). https://doi.org/10.15403/jgld.2014.1121.271.kby
  10. Z. Liyuan X. Xinhua, "The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism" Bioscience Reports, Vol. 38, No. 2, BSR20171234, (2018).
  11. H. Man S. Jin, "Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis", Annals of Translational Medicine, Vol. 7, No. 5, pp. 99, (2019). https://doi.org/10.21037/atm.2019.01.61
  12. C. Barthow, K. Wickens, T. Stanley, "The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy", BMC Pregnancy And Childbirth, Vol. 16, No. 1, pp. 133, (2016). https://doi.org/10.1186/s12884-016-0923-y
  13. E. Widen, L. Kahn, P. Cirillo, K. Cohn, P. Factor, "Prepregnancy overweight and obesity are associated with impaired child neurodevelopment", Maternal & Child Nutrition, Vol. 14, No. 1, e12481, (2018). https://doi.org/10.1111/mcn.12481
  14. J. Zheng, Q. Feng, S. Zheng, X. Xiao, "The effects of probiotics supplementation on metabolic health in pregnant women: An evidence based meta-analysis", PLoS One, Vol. 13, No. 5, e0197771, (2018). https://doi.org/10.1371/journal.pone.0197771
  15. J. Zhenhu, P. Xiaoyang, L. Jiaping, "Reduced-Fat Response of Lactobacillus casei subsp. casei SY13 on a Time and Dose-Dependent Model", Frontiers in Microbiology, Vol. 9, pp. 3200, (2018). https://doi.org/10.3389/fmicb.2018.03200
  16. I. Sofie, N. Lisbeth, M. Emma, "Effects of probiotics (Vivomixx$^{(R)}$) in obese pregnant women and their newborn: study protocol for a randomized controlled trial", Bio med, Vol. 11, No. 17, pp. 491, (2016).
  17. ACOG, "physical activity and exercise during pregnancy and the postpartum period", Obstet Gynecol, Vol. 126, pp. 135-142, (2015) https://doi.org/10.1097/AOG.0000000000001214
  18. ACSM, "Guidelines for exercise testing and prescription", Philadelpia: Lippincott Williams & Wilkins, (2014)
  19. FAO, "Guidelines for the Evaluation of Probiotics in Food", Gut Microbes, Vol. 9, No. 2, pp. 115-130, (2018). https://doi.org/10.1080/19490976.2017.1372077
  20. M. Alice, B. Javad, B. Zach, M. Darya, D. Dustin, R. Heeney, L. Maria, Marco, M. Carolyn, "Supplementation of Lactobacillus plantarum Improves Markers of Metabolic Dysfunction Induced by a High Fat Diet", Journal of Proteome Research, Vol. 8, pp. 2790-2802, (2018).
  21. R. Slykerman, F. Hood, T. Wickens, C. Barthow, "Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial", EBio Medicine, Vol. 24, pp. 159-165, (2017).
  22. K.L. Wickens, C.A. Barthow, R. Murphy, P.R. Abels, R.M. Maude, P.R. Stone, E.A. Mitchell, T.V. Stanley, G.L. Purdie, J.M. Kang, F.E. Hood, J.L. Rowden, P.K. Barnes, P.F. Fitzharris, J. Crane, "Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial", British Journal of Nutrition, Vol. 117, No. 6, pp. 804-813, (2017). https://doi.org/10.1017/S0007114517000289
  23. C. Carolina, D. Marlos, S. Alan, "Efficacy of Regular Exercise During Pregnancy on the Prevention of Postpartum Depression", JAMA Netw Open, Vol. 2, No. 1, pp. 186861, (2019). https://doi.org/10.1001/jamanetworkopen.2018.6861
  24. S. Dilek, Y. Guder, "The effect of pregnancy Pilates-assisted childbirth preparation training on childbirth fear and neonatal outcomes", Quality & Quantity, Vol. 52, No. 6, pp. 2667-2679, (2018). https://doi.org/10.1007/s11135-018-0682-0
  25. R. Barakat, M. Pelaez, Y. Cordero, M. Perales, "Exercise during pregnancy protects against hypertension and macrosomia: randomized clinical trial", American Journal of Obstet Gynecol, Vol. 214, No. 5, pp. 1-8, (2015).
  26. H. Hyun, C. Yong, "Effects of 12-weeks pilates mat exercise on body composition, delivery confidence, and neck disability index in pregnant women", Sport Science, Vol. 36, No. 2, pp. 43-55, (2019). https://doi.org/10.46394/ISS.36.2.5
  27. M. Melissa, M. BNB, "Pilates program design and health benefits for pregnant women: A practitioners' survey", Journal of Bodywork and Movement Therapies, Vol. 22, No. 2, pp. 411-417, (2018). https://doi.org/10.1016/j.jbmt.2017.05.015
  28. A. Everard, S. Matamoros, L. Geurts, N. Delzenne, P. Cani, "Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice", Journal of Molecular Biology, Vol. 5, No. 3, pp. 01011-14, (2014).
  29. S. Emily, C. Judith, T. Joanna, H. Shanshan, A. Caroline, M. Philippa, "Combined diet and exercise interventions for preventing gestational diabetes mellitus, Ochrane Database of Systematic Reviews, Vol. 11, No. 11, CD010443, (2017).
  30. C. Evans, J. LePard, J. Kwak, "Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity", PLoS One, Vol. 9, No. 3, e92193, (2014) https://doi.org/10.1371/journal.pone.0092193
  31. J. Lambert, J. Myslicki, M. Bomhof, D. Belke, J. Shearer, R. Reimer, "Exercise training modifies gut microbiota in normal and diabetic mice", Applied Physiology, Nutrition, and Metabolism, Vol. 40, No. 7, pp. 749-52, (2015). https://doi.org/10.1139/apnm-2014-0452
  32. M. Eveliina, P. Juha, P. Ahtiainen, "Six-Week Endurance Exercise Alters Gut Metagenome That Is not Reflected in Systemic Metabolism in Over-weight Women", Frontiers in Microbiology, Vol. 2323, doi: 10.3389/fmicb.2018.02323, (2018).
  33. A. Jarde, A.M. Lewis-Mikhael, P. Moayyedi, J.C. Stearns, S.M. Collins, J. Beyene, S.D. McDonald, "Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis", BMC Pregnancy And Childbirth, Vol. 18, No. 1, pp. 14, (2018). https://doi.org/10.1186/s12884-017-1629-5
  34. R. Hage, E. Hernandez-Sanabria, T. Van de Wiele, "Emerging Trends in Smart Probiotics Functional Consideration for the Development of Novel Health and Industrial Applications", Frontiers in Psychology, Vol. 8, pp. 1889, (2017). https://doi.org/10.3389/fpsyg.2017.01889
  35. S. Sabico, A. Al-Mashharawi, N.M. Al-Daghri, S. Yakout, A.M. Alnaami, M.S. Alokail, P.G. McTernan, "Effects of a multi-strain probiotic supplement for 12 weeks in circulating endotoxin levels and cardiometabolic profiles of medication naive T2DM patients: a randomized clinical trial", Journal of Translational Medicine, Vol. 15, No. 1, pp. 249, (2017). https://doi.org/10.1186/s12967-017-1354-x
  36. Z. Jia, X. Pang, "Reduced-Fat Response of Lactobacillus casei subsp. casei SY13 on a Time and Dose-Dependent Model", Frontiers in Microbiology, Vol. 9, pp. 3200, (2018). https://doi.org/10.3389/fmicb.2018.03200
  37. S. Lim, J. Jeong, K. Woo, M. Han, D. Kim, "Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression", Nutrition Research, Vol. 36, No. 4, pp. 337-348, (2016). https://doi.org/10.1016/j.nutres.2015.12.001
  38. A. Hartstra, K. Bouter, F. Backhed, M. Nieuwdorp, "Insights into the role of the microbiome in obesity and type 2 diabetes", Diabetes Care, Vol. 38, No. 1, pp. 159-65, (2015). https://doi.org/10.2337/dc14-0769
  39. E. Barengolts, "Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: review of randomized controlled trials", Endocrine Practice, Vol. 22, No. 10, pp. 1224-1234, (2016). https://doi.org/10.4158/EP151157.RA
  40. P. Young, K. Seulki, L. Dong, "The Inhibitory Effect of L. plantarum Q180 on Adipocyte Differentiation in 3T3-L1 and Reduction of Adipocyte Size in Mice Fed High-fat Diet", Korean Journal for Food Science of Animal Resources, Vol. 38, No. 1, pp. 99-109, (2018). https://doi.org/10.5851/kosfa.2018.38.1.99
  41. C. Wu, W. Weng, W. Lai, H. Tsai, W. Liu, "Effect of Lactobacillus plantarum Strain K21 on High-Fat Diet-Fed Obese Mice", Evidence-Based Complementary and Alternative Medicine, doi: 10.1155/2015/391767, (2015).
  42. K. Lindsay, L. Brennan, M. Kennelly, O. Maguire, T. Smith, S. Curran, M. Coffey, M.E. Foley, M. Hatunic, F. Shanahan, F. McAuliffe, "Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial", American Journal of Obstetrics & Gynecology, Vol. 222, No. 4, pp. 496, (2015).
  43. Z. Asemi, M. Samimi, Z. Tabassi, M. Naghibi, A. Rahimi, H. Khorammian, A. Esmaillzadeh, "Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial", European Journal of Clinical Nutrition, Vol. 67, No. 1, pp. 71-74, (2013). https://doi.org/10.1038/ejcn.2012.189
  44. J.F. Briffa, A.J. McAinch, T. Romano, M.E. Wlodek, D.H. Hryciw, "Leptin in pregnancy and development: a contributor to adulthood disease?", Department of Physiology, University of Melbourne, Vol. 308, No. 5, pp. 335-350, (2014).
  45. B. Sun, N. Liang, E.R. Ewald, R.H. Purcell, G.J. Boersma, J. Yan, T.H. Moran, K.L. K. Tamashir, "Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation", American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 305, No. 9, pp. 1076-1084, (2013) https://doi.org/10.1152/ajpregu.00566.2012
  46. F.A. Duca, T.D. Swartz, Y. Sakar, M. Covasa, "Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota", PLoS One, Vol. 7, No. 6, e39748, (2012). https://doi.org/10.1371/journal.pone.0039748
  47. O. Queipo, L. Seoane, M. Murri, M. Pardo, J. Gomez, F. Cardona, F. Casanueva, F. Tinahones, "Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels", PLoS One, Vol. 8, No. 5, e65465, (2013). https://doi.org/10.1371/journal.pone.0065465
  48. Q. Liping, W. Jean, L. Samuel, N. Amanda, S. Jerome, W. William, J. Hay, S. Jianhua, "Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice", Diabetes, Vol. 66, No. 5, pp. 1126-1135, (2017). https://doi.org/10.2337/db16-1096
  49. B. Vahideh, J. Shima, A. Naheed, J. Mohama, H. Fatemeh, "Effects of Probiotic and Prebiotic Supplementation on Leptin, Adiponectin, and Glycemic Parameters in Non-alcoholic Fatty Liver Disease: A Randomized Clinical Trial", Middle East Journal of Digestive Diseases, Vol. 9, No. 3, pp. 150-157, (2017). https://doi.org/10.15171/mejdd.2017.66
  50. A. Kylie, D. McLachlan, J. Alicia, P. Frank, "Do adiponectin, $TNF{\alpha}$, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy", Diabetes Metabolism Research and Reviews, Vol. 22, No. 2, pp. 131-138, (2006). https://doi.org/10.1002/dmrr.591
  51. G. Moller, M. Goulart, B. Nicoletto, F. Alves, C. Schneider, "Supplementation of Probiotics and Its Effects on Physically Active Individuals and Athletes", International Journal of Sport Nutrition and Exercise Metabolism, Vol. 24, pp. 1-30, (2019). https://doi.org/10.1123/ijsnem.2014-0026
  52. N. Ibrahim, A. Muhamad, F. Ooi, J. Meor, C. Chen, "The effects of combined probiotic ingestion and circuit training on muscular strength and power and cytokine responses in young males", Applied Physiology, Nutrition, and Metabolism, Vol. 43, No. 2, pp. 180-186, (2018). https://doi.org/10.1139/apnm-2017-0464
  53. H. Fang, R. Judd, "Adiponectin Regulation and Function", Comprehensive Physiology, Vol. 8, No. 3, pp. 1031-1063, (2018).
  54. M.H. Rouhani, A. Hadi, E. Ghaedi, M. Salehi, A. Mahdavi, H. Mohammadi, "Do probiotics, prebiotics and synbiotics affect adiponectin and leptin in adults? A systematic review and meta-analysis of clinical trials", Clinical Nutrition, Vol. 38, No. 5, pp. 2031-2037, (2018). https://doi.org/10.1016/j.clnu.2018.09.033
  55. N. Kobyliak, T. Falalyeyeva, G. Mykhalchyshyn, D. Kyriienko, I. Komissarenko, "Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial", Diabetology & Metabolic Syndrome, Vol. 12, No. 5, pp. 617-624, (2018). https://doi.org/10.1016/j.dsx.2018.04.015
  56. L. Yuan, W. Yanyun, D. Xiaoyan, "Serum Levels of TNF-$\alpha$ and IL-6 Are Associated With Pregnancy-Induced Hypertension", Journal of Human Reproductive Sciences, Vol. 23, No. 10, pp. 1402-8, (2016). https://doi.org/10.1177/1933719116641760
  57. F. Maillard, E. Vazeille, P. Sauvanet, "Preventive Effect of Spontaneous Physical Activity on the Gut-Adipose Tissue in a Mouse Model That Mimics Crohn's Disease Susceptibility", Cells, Vol. 8, No. 1, pp. 33, (2019). https://doi.org/10.3390/cells8010033
  58. D. Groeger, L. O'Mahony, E.F. Murphy, J.F. Bourke, T.G. Dinan, B. Kiely, F. Shanahan, E.M.M. Quigley, "Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut", Gut Microbes, Vol. 4, No. 4, pp. 325-339, (2014).
  59. J. Instanes, A. Halmoy, A. Engeland, J. Haavik, K. Furu, K. Klungsoyr, "Attention-Deficit Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases", Biological Psychiatry, Vol. 81, No. 5, pp. 452-459, (2017). https://doi.org/10.1016/j.biopsych.2015.11.024
  60. C. Yuyi, L. Zhe, T. Kian, L. Huijuan, T. Xiaomei, L. Yu, "Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status", Frontiers in Cellular and Infection Microbiology, Vol. 9, pp. 254, (2019). https://doi.org/10.3389/fcimb.2019.00254
  61. N. Yu, H. Cui, X. Chen, Y. Chang, "Changes of serum pentraxin-3 and hypersensitive CRP levels during pregnancy and their relationship with gestational diabetes mellitus", PLoS One, Vol. 14, No. 11, e0224739, (2019). https://doi.org/10.1371/journal.pone.0224739
  62. Y. Zhou, C. Qi, S. Li, X. Shao, S. Mou, Z. Ni, "Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function", Cell Physiol Biochem, Vol. 51, No. 3, pp. 1119-1133, (2018). https://doi.org/10.1159/000495491
  63. N. Kobyliak, C. Conte, G. Cammarota, A. Haley, I. Styriak, L. Gaspar, J. Fusek, L. Rodrigo, P. Kruzliak, "Probiotics in prevention and treatment of obesity: a critical view", Nutrition & Metabolism, Vol. 13, pp. 14, (2016). https://doi.org/10.1186/s12986-016-0067-0
  64. J. Dugoua, M. Machado, X. Zhu, X. Chen, "Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp", Journal of Obstetrics and Gynaecology Canada, Vol. 31, No. 6, pp. 542-552, (2009). https://doi.org/10.1016/S1701-2163(16)34218-9