Key points
- Synbiotic supplements could help to modulate intestinal permeability
- Reviews of the evidence show benefits from synbiotic supplementation on a range of health conditions, including cancer and cardiometabolic, neurological, and gastrointestinal conditions
Synbiotic supplementation is a relatively new concept (when compared to supplementing with pre- and probiotics) that has a large body of emerging research on its potential uses for health.
[See the previous article on the overall health effects of Synbiotics]
Synbiotics and ‘leaky gut’
Synbiotics might play a role in modulating inappropriate gut permeability (commonly called ‘leaky gut’). The gut wall is permeable by nature to allow for greater or lesser ingress of nutrients into the system. The amount of permeability shifts constantly and is influenced by many factors. Increased intestinal permeability which may be inappropriate for optimal immune, allergy, and inflammatory modulation is influenced by diet and lifestyle factors, especially the gliadin protein (a component of gluten) and by small intestinal bacterial overgrowth and dysbiosis.1 Therefore, our diet and lifestyle, including factors like a typical Western-style diet high in gluten-containing ultra-refined foods, sugar, and other factors like stress and lack of movement (which affect gut motility) are likely to play a role in ‘leaky gut’ and resultant immunological and inflammatory challenges. A primary modulator of intestinal permeability is the protein zonulin. Synbiotic supplementation reduces zonulin levels,2 and so, might play a role in reducing excessive intestinal permeability and might even help to reduce muscle wasting by reducing intestinal permeability. A 2021 review by Krimpen and colleagues found that Lactobacillus and Bifidobacterium reduce muscle wasting in mice and that there is an association between gut permeability and muscle mass. Thus, they proposed that some interaction of lactate, butyrate, and reduced inflammation from probiotic or synbiotic supplementation might help to prevent muscle wasting.3
Synbiotics in critical illness and surgery
Synbiotics and probiotics increase levels of the beneficial short-chain fatty acids acetic acid, butyric acid, and propionic acid, and reduce c-reactive protein and interleukin-6. They have been shown to reduce surgery-related complications including abdominal distention, diarrhoea, pneumonia, sepsis, surgery site and urinary tract infection, and reduce the duration of antibiotic therapy, postoperative pyrexia, time of fluid introduction, time-to-solid diet, and duration of hospital stay.4-11 It has been concluded that perioperative synbiotics “clearly reduce infection after liver surgery”.12
A 2016 review that compared the effects of synbiotics and probiotics found that there was a greater improvement in infection rates in studies of probiotics compared to those conducted on synbiotics, however, the authors noted there was limited clinical data available at the time for synbtioics.13
Metabolic disorders
Prediabetes & non-alcoholic fatty liver disease
Reviews of randomised controlled trials have shown that synbiotic supplementation can improve body mass, blood glucose, insulin, LDL and total cholesterol, triglycerides, inflammatory markers c-reactive protein and tumour necrosis factor-alpha (TNF-α), and liver enzymes alanine transaminase and aspartate transaminase14 and GGT15 levels among patients with non-alcoholic fatty liver disease (NAFLD). 14, 16, 17
Diabetes
Synbiotics supplementation significantly improves fasting blood glucose, insulin, HOMA-IR, insulin sensitivity (QUICKI) and triglycerides, V-LDL, LDL, HDL and total cholesterol.18-20 Synbiotic supplementation also reduces the inflammatory markers TNF-α, malondialdehyde, and c-reactive protein in people with diabetes21, 22 while also increasing total antioxidant capacity and glutathione.22
Obesity
Synbiotic supplementation is known to reduce fasting insulin and triglyceride levels, an effect also observed in people with obesity.23A meta-analysis of 23 randomized trials indicated that supplementation with synbiotic can decrease body weight and waist circumference.24 A 2019 review also found that while overall no significant effects from probiotic or synbiotic supplementation were observed for metabolic and anthropometric markers in children and teens, sub-group analysis revealed a significant reduction in body mass index (BMI) z-score in the synbiotic supplemented groups.25 Similarly, another review and meta-analysis from the same year found no difference in body weight or BMI but a significant reduction in waist circumference (of less than 1 cm).26 The most recent review in this area included here (from 2020) found significant reductions in BMI, total body fat, waist circumference, and waist height ratio27 (an important indicator of metabolic health and disease risk).
Blood pressure
Synbiotics have been shown to reduce systolic blood pressure by around 3 mmHg and blood pressure reducing effects were greater with longer-term supplementation (i.e., > 12 weeks) and in younger people.28
Respiratory infections
Overall, synbiotic interventions reduce the incidence rate of respiratory infections by ~16%. Subgroup analysis also suggested more prominent effects of synbiotics among adults than infants and children.29
Asthma
In a review of 11 randomised trials including over 1600 children, while no association was found between probiotic use and asthma risk, a significant reduction in asthma risk was observed in those taking pre- or synbiotics.30
Pneumonia
Network meta-analysis has shown that synbiotics, especially Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophiles, B. longum + L. bulgaricus + S. thermophiles and Lactobacillus rhamnosus were superior to placebo in preventing ventilator-assisted pneumonia. Analysis was performed to rank the treatments, finding that the most efficacious treatment for preventing pneumonia of this type was B. longum + L. bulgaricus + S. thermophiles.31
Pancreatitis
Patients treated with pro-, pre-, or synbiotics had significantly shorter hospital stays and a lower risk of organ failure compared to control.32
Cancer
Both probiotics and synbiotics might help prevent colorectal cancer, likely through mechanisms including modulating the intestinal microbiota, reducing inflammation, inducing apoptosis and inhibiting cancer cell growth, modulation of immune responses and cell proliferation, enhanced intestinal barrier function, modulation of oxidative stress, and production of anti-carcinogenic compounds in the gut.33 Synbiotics also have a positive effect on diarrhoea, symptomatic intestinal obstructions, surgical infections and pneumonia in cancer patients undergoing colorectal resection.34
Pregnancy
Synbiotic supplementation might reduce anxiety in perinatal women.35 Synbiotic supplementation also reduces insulin and improves insulin homeostasis in pregnant women,36 and in those with gestational diabetes reduces inflammation, improves antioxidant capacity, and reduces insulin and very-low-density lipoprotein. Supplementation during pregnancy was also associated with reduced risk of hyperbilirubinemia in the newborn and improved birth weight.37
Mental health
Synbiotics may modulate depression and anxiety but at this time, the research is inconclusive and pro- and synbiotics might affect mental health conditions in a strain-specific manner.38
Irritable bowel syndrome
Synbiotics significantly improve global IBS scores compared to placebo.39
Chronic kidney disease
Synbiotic supplementation significantly reduces inflammatory markers CRP and MDA11, 40 while increasing the antioxidant glutathione in chronic kidney disease patients, as compared to placebo. Subgroup analyses showed that other key factors, such as the duration of intervention, participants’ baseline body mass index (BMI), type of intervention, and age, had an effect of microbial therapies on outcomes.40 Synbiotics might also reduce total cholesterol, fasting blood glucose, and improve insulin sensitivity.11
Pancreatitis
Use of pre-, pro-, and synbiotics shorten the length of hospital stay in severe acute pancreatitis.41
Autism spectrum disorder
A 2021 review by Tan and colleagues concluded that at this time results from the extant research do not support that probiotics are beneficial for ASD but that synbiotics appear to be effective in reducing some behavioural symptoms of ASD.42
Autoimmune conditions
Overall, pro- and synbiotic therapies have been shown to reduce inflammatory markers (CRP, IL-6, TNF-a, MDA) and improve insulin homeostasis in people with autoimmune conditions.43
Inflammatory bowel diseases
Pro-, pre-, and synbiotics increase Bifidobacteria and can improve remission rates and reduce disease activity in ulcerative colitis. Synbiotics appear to be more effective than either pre- or probiotics.44 Synbiotics also significantly improve endoscopic and histological scores, clinical disease activity, c-reactive protein, intestinal microbiota, bowel habits and levels of mRNA, TNF-a, interleukin1a, interleukin-10 and modulates pro- and anti-inflammatory colonic cytokines.45
Polycystic ovary syndrome
Pro-, and synbiotic supplementation reduce insulin and triglycerides,46 free androgens and the inflammatory marker MDA, and increases sex hormone-binding globulin and nitric oxide in women with PCOS.47 Effects on fasting blood glucose, HOMA-IR, c-reactive protein, and total testosterone were previously thought to be equivocal,46, 48 but meta-analysis published in 2020 and 2021 suggest improvement in insulin and insulin homeostasis.49, 50 In a 2018 review it was noted that although significant, the reduction in triglycerides was negligible.46 However, this amounted to a reduction of ~0.2 mmol/L, which is clinically meaningful. Subgroup analysis has also suggested that probiotics are associated with greater reductions in testosterone and post-prandial glucose while synbiotics resulted in a more pronounced reduction in fasting blood insulin.49
Diarrhoea
Treatment with pro- or synbiotics significantly reduces the duration of diarrhoea,51, 52 hospitalisations,51 and hospital stay-length52 in severe cases of diarrhoea in children.
Stomach ulcers
Helicobacter pylori overgrowth is commonly implicated as either causal or comorbid with gastric ulcers. Synbiotics might help to reduce complications of stomach ulcers by improving H. pylori eradication rates and reducing adverse events of antibiotic therapy.53
Cognition
Early studies in elderly people with cognitive decline suggest that pro- and synbiotics might improve cognition.54
Eczema
A meta-analysis of 6 randomised controlled trials found significant reductions in the clinical severity of atopic eczema in children when mixed bacteria were used and by children over 1 year of age.55
Summary
Synbiotics offer the potential to improve a host of health conditions. They have been demonstrated to positively influence the gut microbiota and have demonstrated functional benefits for a range of health conditions. Their effects are likely to be due to gut-modulated and associated improvements in immunological and inflammatory modulation.
Check out Part 1. The Health Benefits of Synbiotics
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References
1. Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. 2011;91(1):151-75.
2. Ramezani Ahmadi A, Sadeghian M, Alipour M, Ahmadi Taheri S, Rahmani S, Abbasnezhad A. The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis. Iran J Public Health. 2020;49(7):1222-31.
3. van Krimpen SJ, Jansen FAC, Ottenheim VL, Belzer C, van der Ende M, van Norren K. The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting, a Systematic Review—Gut Permeability as Potential Treatment Target. Nutrients. 2021;13(4):1115.
4. Skonieczna-Żydecka K, Kaczmarczyk M, Łoniewski I, Lara LF, Koulaouzidis A, Misera A, et al. A Systematic Review, Meta-Analysis, and Meta-Regression Evaluating the Efficacy and Mechanisms of Action of Probiotics and Synbiotics in the Prevention of Surgical Site Infections and Surgery-Related Complications. Journal of Clinical Medicine. 2018;7(12):556.
5. Lytvyn L, Quach K, Banfield L, Johnston BC, Mertz D. Probiotics and synbiotics for the prevention of postoperative infections following abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Journal of Hospital Infection. 2016;92(2):130-9.
6. Kasatpibal N, Whitney JD, Saokaew S, Kengkla K, Heitkemper MM, Apisarnthanarak A. Effectiveness of Probiotic, Prebiotic, and Synbiotic Therapies in Reducing Postoperative Complications: A Systematic Review and Network Meta-analysis. Clinical Infectious Diseases. 2017;64(suppl_2):S153-S60.
7. Yang Z, Wu Q, Liu Y, Fan D. Effect of Perioperative Probiotics and Synbiotics on Postoperative Infections After Gastrointestinal Surgery: A Systematic Review With Meta-Analysis. Journal of Parenteral and Enteral Nutrition. 2017;41(6):1051-62.
8. Kinross JM, Markar S, Karthikesalingam A, Chow A, Penney N, Silk D, et al. A Meta-Analysis of Probiotic and Synbiotic Use in Elective Surgery. Journal of Parenteral and Enteral Nutrition. 2013;37(2):243-53.
9. Wu X-D, Liu M-M, Liang X, Hu N, Huang W. Effects of perioperative supplementation with pro-/synbiotics on clinical outcomes in surgical patients: A meta-analysis with trial sequential analysis of randomized controlled trials. Clinical Nutrition. 2018;37(2):505-15.
10. Arumugam S, Lau CSM, Chamberlain RS. Probiotics and Synbiotics Decrease Postoperative Sepsis in Elective Gastrointestinal Surgical Patients: a Meta-Analysis. Journal of Gastrointestinal Surgery. 2016;20(6):1123-31.
11. Zeng J, Ji Y, Liang B, Zhang G, Chen D, Zhu M, et al. The effect of pro/synbiotics on postoperative infections in colorectal cancer patients: A systematic review and meta-analysis. Complementary Therapies in Clinical Practice. 2021;43:101370.
12. Kahn J, Pregartner G, Schemmer P. Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut–Liver Axis—A Systematic Review and Meta-Analysis. Nutrients. 2020;12(8):2461.
13. Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Critical Care. 2016;20(1):262.
14. Khan MY, Mihali AB, Rawala MS, Aslam A, Siddiqui WJ. The promising role of probiotic and synbiotic therapy in aminotransferase levels and inflammatory markers in patients with nonalcoholic fatty liver disease – a systematic review and meta-analysis. European Journal of Gastroenterology & Hepatology. 2019;31(6):703-15.
15. Khalesi S, Johnson DW, Campbell K, Williams S, Fenning A, Saluja S, et al. Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis. Eur J Nutr. 2018;57(6):2037-53.
16. Hadi A, Mohammadi H, Miraghajani M, Ghaedi E. Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials: Synbiotic supplementation and NAFLD. Critical Reviews in Food Science and Nutrition. 2019;59(15):2494-505.
17. Liu L, Li P, Liu Y, Zhang Y. Efficacy of Probiotics and Synbiotics in Patients with Nonalcoholic Fatty Liver Disease: A Meta-Analysis. Digest Dis Sci. 2019;64(12):3402-12.
18. Tabrizi R, Moosazadeh M, Lankarani KB, Akbari M, Heydari ST, Kolahdooz F, et al. The Effects of Synbiotic Supplementation on Glucose Metabolism and Lipid Profiles in Patients with Diabetes: a Systematic Review and Meta-Analysis of Randomized Controlled Trials. Probiotics and Antimicrobial Proteins. 2018;10(2):329-42.
19. Mahboobi S, Rahimi F, Jafarnejad S. Effects of Prebiotic and Synbiotic Supplementation on Glycaemia and Lipid Profile in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Adv Pharm Bull. 2018;8(4):565-74.
20. Bock PM, Telo GH, Ramalho R, Sbaraini M, Leivas G, Martins AF, et al. The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2021;64(1):26-41.
21. Tabrizi R, Ostadmohammadi V, Lankarani KB, Akbari M, Akbari H, Vakili S, et al. The effects of probiotic and synbiotic supplementation on inflammatory markers among patients with diabetes: A systematic review and meta-analysis of randomized controlled trials. European Journal of Pharmacology. 2019;852:254-64.
22. Zheng HJ, Guo J, Jia Q, Huang YS, Huang W-J, Zhang W, et al. The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research. 2019;142:303-13.
23. Beserra BTS, Fernandes R, do Rosario VA, Mocellin MC, Kuntz MGF, Trindade EBSM. A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity. Clinical Nutrition. 2015;34(5):845-58.
24. Hadi A, Alizadeh K, Hajianfar H, Mohammadi H, Miraghajani M. Efficacy of synbiotic supplementation in obesity treatment: A systematic review and meta-analysis of clinical trials. Critical Reviews in Food Science and Nutrition. 2020;60(4):584-96.
25. Mohammadi H, Ghavami A, Hadi A, Askari G, Symonds M, Miraghajani M. Effects of pro-/synbiotic supplementation on anthropometric and metabolic indices in overweight or obese children and adolescents: A systematic review and meta-analysis. Complementary Therapies in Medicine. 2019;44:269-76.
26. Suzumura EA, Bersch-Ferreira ÂC, Torreglosa CR, da Silva JT, Coqueiro AY, Kuntz MGF, et al. Effects of oral supplementation with probiotics or synbiotics in overweight and obese adults: a systematic review and meta-analyses of randomized trials. Nutrition reviews. 2019;77(6):430-50.
27. Cao S, Ryan PM, Salehisahlabadi A, Abdulazeem HM, Karam G, Černevičiūtė R, et al. Effect of probiotic and synbiotic formulations on anthropometrics and adiponectin in overweight and obese participants: A systematic review and meta-analysis of randomized controlled trials. Journal of King Saud University – Science. 2020;32(2):1738-48.
28. Hadi A, Pourmasoumi M, Kazemi M, Najafgholizadeh A, Marx W. Efficacy of synbiotic interventions on blood pressure: a systematic review and meta-analysis of clinical trials. Critical Reviews in Food Science and Nutrition. 2021:1-11.
29. Chan CKY, Tao J, Chan OS, Li H-B, Pang H. Preventing Respiratory Tract Infections by Synbiotic Interventions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Advances in Nutrition. 2020;11(4):979-88.
30. Wawryk-Gawda E, Markut-Miotła E, Emeryk A. Postnatal probiotics administration does not prevent asthma in children, but using prebiotics or synbiotics may be effective potential strategies to decrease the frequency of asthma in high-risk children–a meta-analysis of clinical trials. Allergologia et Immunopathologia. 2021;49(4):4-14.
31. Fan Q-L, Yu X-M, Liu Q-X, Yang W, Chang Q, Zhang Y-P. Synbiotics for prevention of ventilator-associated pneumonia: a probiotics strain-specific network meta-analysis. Journal of International Medical Research. 2019;47(11):5349-74.
32. Yu C, Zhang Y, Yang Q, Lee P, Windsor JA, Wu D. An Updated Systematic Review With Meta-analysis: Efficacy of Prebiotic, Probiotic, and Synbiotic Treatment of Patients With Severe Acute Pancreatitis. Pancreas. 2021;50(2):160-6.
33. Cruz BCS, Sarandy MM, Messias AC, Gonçalves RV, Ferreira CLLF, Peluzio MCG. Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: a systematic review. Nutrition reviews. 2020;78(8):667-87.
34. He D, Wang H-Y, Feng J-Y, Zhang M-M, Zhou Y, Wu X-T. Use of pro-/synbiotics as prophylaxis in patients undergoing colorectal resection for cancer: A meta-analysis of randomized controlled trials. Clinics and Research in Hepatology and Gastroenterology. 2013;37(4):406-15.
35. Desai V, Kozyrskyj AL, Lau S, Sanni O, Dennett L, Walter J, et al. Effectiveness of Probiotic, Prebiotic, and Synbiotic Supplementation to Improve Perinatal Mental Health in Mothers: A Systematic Review and Meta-Analysis. Frontiers in psychiatry. 2021;12:622181-.
36. Luo C, Wan J, Rao Z, Zhang Y. Synbiotic supplementation for glycemic status in pregnant women: a meta-analysis of randomized clinical trials. Gynecological Endocrinology. 2021;37(2):146-51.
37. Hao Y, Zhou L, Ding C, Wu J, Chen X, Ng DM, et al. Probiotics and synbiotics show clinical efficacy in treating gestational diabetes mellitus: A meta-analysis. Primary Care Diabetes. 2021.
38. Vaghef-Mehrabany E, Maleki V, Behrooz M, Ranjbar F, Ebrahimi-Mameghani M. Can psychobiotics “mood” ify gut? An update systematic review of randomized controlled trials in healthy and clinical subjects, on anti-depressant effects of probiotics, prebiotics, and synbiotics. Clinical Nutrition. 2020;39(5):1395-410.
39. Asha MZ, Khalil SFH. Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis. Sultan Qaboos Univ Med J. 2020;20(1):e13-e24.
40. Zheng HJ, Guo J, Wang Q, Wang L, Wang Y, Zhang F, et al. Probiotics, prebiotics, and synbiotics for the improvement of metabolic profiles in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition. 2021;61(4):577-98.
41. Tian X, Pi Y-P, Liu X-L, Chen H, Chen W-Q. Supplemented Use of Pre-, Pro-, and Synbiotics in Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis of 13 Randomized Controlled Trials. Frontiers in Pharmacology. 2018;9(690).
42. Tan Q, Orsso CE, Deehan EC, Kung JY, Tun HM, Wine E, et al. Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review. Autism Research. 2021;14(9):1820-36.
43. Askari G, Ghavami A, Shahdadian F, Moravejolahkami AR. Effect of synbiotics and probiotics supplementation on autoimmune diseases: A systematic review and meta-analysis of clinical trials. Clinical Nutrition. 2021;40(5):3221-34.
44. Zhang X-F, Guan X-X, Tang Y-J, Sun J-F, Wang X-K, Wang W-D, et al. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Nutr. 2021;60(5):2855-75.
45. Rufino MN, da Costa AL, Jorge EN, Paiano VF, Camparoto ML, Keller R, et al. Synbiotics improve clinical indicators of ulcerative colitis: systematic review with meta-analysis. Nutrition reviews. 2021.
46. Heshmati J, Farsi F, Yosaee S, Razavi M, Rezaeinejad M, Karimie E, et al. The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: a Systematic Review and Meta-Analysis of Randomized Clinical Trials. Probiotics and Antimicrobial Proteins. 2019;11(4):1236-47.
47. Shamasbi SG, Ghanbari-Homayi S, Mirghafourvand M. The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: a systematic review and meta-analysis. Eur J Nutr. 2020;59(2):433-50.
48. Hadi A, Moradi S, Ghavami A, Khalesi S, Kafeshani M. Effect of probiotics and synbiotics on selected anthropometric and biochemical measures in women with polycystic ovary syndrome: a systematic review and meta-analysis. European Journal of Clinical Nutrition. 2020;74(4):543-7.
49. Cozzolino M, Vitagliano A, Pellegrini L, Chiurazzi M, Andriasani A, Ambrosini G, et al. Therapy with probiotics and synbiotics for polycystic ovarian syndrome: a systematic review and meta-analysis. Eur J Nutr. 2020;59(7):2841-56.
50. Miao C, Guo Q, Fang X, Chen Y, Zhao Y, Zhang Q. Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis. Journal of International Medical Research. 2021;49(7):03000605211031758.
51. Yang B, Lu P, Li M-X, Cai X-L, Xiong W-Y, Hou H-J, et al. A meta-analysis of the effects of probiotics and synbiotics in children with acute diarrhea. Medicine. 2019;98(37):e16618-e.
52. Kambale RM, Nancy FI, Ngaboyeka GA, Kasengi JB, Bindels LB, Van der Linden D. Effects of probiotics and synbiotics on diarrhea in undernourished children: Systematic review with meta-analysis. Clinical Nutrition. 2021;40(5):3158-69.
53. Pourmasoumi M, Najafgholizadeh A, Hadi A, Mansour-Ghanaei F, Joukar F. The effect of synbiotics in improving Helicobacter pylori eradication: A systematic review and meta-analysis. Complementary Therapies in Medicine. 2019;43:36-43.
54. Coutts L, Ibrahim K, Tan QY, Lim SER, Cox NJ, Roberts HC. Can probiotics, prebiotics and synbiotics improve functional outcomes for older people: a systematic review. European Geriatric Medicine. 2020;11(6):975-93.
55. Chang Y-S, Trivedi MK, Jha A, Lin Y-F, Dimaano L, García-Romero MT. Synbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials. JAMA Pediatrics. 2016;170(3):236-42.
