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Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.
Shu, Q, Kang, C, Li, J, Hou, Z, Xiong, M, Wang, X, Peng, H
PloS one. 2024;19(1):e0296733
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The gut microbiome is thought to play a role in thyroid disorders, mediated by regulating iodine uptake, degradation and enterohepatic cycling of thyroid hormones, and differences in microbiome composition between patients with thyroid disorders and healthy individuals have been observed. The aim of this systematic review and meta-analysis was to evaluate the effect of pro-, pre- and synbiotics on thyroid function (thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and thyroid stimulating hormone receptor antibody (TRAb)) in patients with and without thyroid disorders. 8 randomised controlled trials including 367 participants were included in the review and meta-analysis. Neither pro-, pre- nor synbiotics had a significant effect on TSH, fT4 or fT3 but pre- and probiotics lead to a significant reduction in TRAb in patients with Graves’ disease.
Abstract
BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.
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Are probiotics, prebiotics, and synbiotics beneficial in primary thyroid diseases? A systematic review with meta-analysis.
Zawadzka, K, Kałuzińska, K, Świerz, MJ, Sawiec, Z, Antonowicz, E, Leończyk-Spórna, M, Abadi, AK, Trofimiuk-Müldner, M, Bała, MM
Annals of agricultural and environmental medicine : AAEM. 2023;30(2):217-223
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Irregularities in intestinal microbial composition are thought to be correlated with thyroid dysfunction. Supplementation of prebiotics, probiotics and synbiotics are gaining momentum in recent times in improving health in general. This systematic review of randomised controlled trials was conducted to summarise the up-to-date evidence on the therapeutic potential of prebiotics, probiotics and synbiotics in the treatment of thyroid disease. The meta-analysis did not show beneficial effects on thyroid hormone balance, BMI or levothyroxine dosage reduction. Supplementation with Lactobacillus and Bifidobacterium resulted in improvement in constipation and a statistically non-significant reduction in thyroid-stimulating hormone in adult participants with hypothyroidism. Further robust long-term studies are required to evaluate the efficacy of prebiotics, probiotics and synbiotics in thyroid disease treatment as the availability of the number of studies included in this systematic review was limited. However, healthcare professionals can use the review to understand the current evidence in this area and the correlation between gut microbial alterations and thyroid disease.
Abstract
INTRODUCTION AND OBJECTIVE A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases. REVIEW METHODS Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054). BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD -0.19 mIU/L; 95% CI -0.43 to 0.06; I2= 0%), and no effect on fT3 levels (MD 0.01 pg/mL; 95% CI-0.16 to 0.18; I2= 0%). Data from single studies indicated no significant change in the levels of fT4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD -8.71 points in the Faecal Incontinence Questionnaire; 95% CI -15.85 to -1.57; I2= 0%). SUMMARY Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.
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Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review.
Avelar-Rodríguez, D, Peña-Vélez, R, Popov, J, Hill, L, Ryan, PM
Revista espanola de enfermedades digestivas. 2023;115(8):418-427
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Non-alcoholic fatty liver disease (NAFLD), as a direct result of the escalating childhood obesity epidemic, is a significant public health issue globally. NAFLD is the most common cause of chronic liver disease in the paediatric population. The aim of this study was to assess the quality of evidence currently available for the use of microbial therapies (i.e., prebiotics, probiotics, and synbiotics) in the treatment of NAFLD in children with obesity. This study was a systematic review and meta-analysis of five randomised controlled studies. Results showed that although there is a range of promising effects on both clinical and biochemical parameters, significant interstudy discrepancies reduce reliability and generalisability of these results. Authors concluded there is insufficient evidence to support the beneficial role of probiotics and synbiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials.
Abstract
BACKGROUND non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.
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Effectiveness of Probiotic, Prebiotic, and Synbiotic Supplementation to Improve Perinatal Mental Health in Mothers: A Systematic Review and Meta-Analysis.
Desai, V, Kozyrskyj, AL, Lau, S, Sanni, O, Dennett, L, Walter, J, Ospina, MB
Frontiers in psychiatry. 2021;12:622181
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Maternal mental health problems in the perinatal period are a global public health challenge. As many as one in five women develop depression and/or anxiety in the postpartum period, making them the most common complications of pregnancy and delivery. The aim of this study was to evaluate the evidence on the administration of prebiotic, probiotic, and/or synbiotic supplements during pregnancy to reduce the risk of mental health problems in the perinatal period. This study is a systemic review and meta-analysis of four studies of which three where included in the qualitative and quantitative synthesis. Results indicate limited evidence about the effectiveness of probiotics administered during pregnancy to reduce the risk of maternal mental health disorders and highlighted the lack of evidence on prebiotics and synbiotics supplementation to inform their use for similar purposes. Authors conclude that there is the need for future trials targeting microbiota interventions that test probiotic/prebiotic/synbiotic interventions that redress specific dysbioses in pregnancy gut microbiota that arise from poor mental health.
Abstract
Introduction: There is an emerging interest in modulating the gut microbiota to target the gut-brain axis and improve maternal mental health in the perinatal period. This systematic review evaluated the effectiveness of prebiotics, probiotics, and synbiotics supplementation during pregnancy to reduce the risk of maternal mental health problems in the perinatal period. Methods: Electronic biomedical databases and clinical trial registries were searched from database inception through August 2020 to identify randomized controlled clinical trials (RCTs) evaluating the effect of probiotic, prebiotic, or synbiotic supplements administered to women during pregnancy on measures of perinatal depression, anxiety, and other mental health outcomes. Study selection, risk of bias appraisal, and data extraction were independently performed by two reviewers. Pooled mean differences (MD) and odds ratios (pOR) with 95% confidence intervals (CI) were calculated in random-effects meta-analyses for the outcomes of interest in the review. Results: From 3,868 studies identified through the search strategy, three RCTs of low risk of bias involving 713 participants were included, all three testing probiotics. There were no differences between probiotics and control groups in the mean depression scores (MD -0.46; 95% CI -2.16, 1.25) at end of follow-up. Although statistical significance was not achieved, probiotics showed an advantage in the proportion of participants scoring below an established cut-off for depression (pOR 0.68; 95% CI 0.43, 1.07). Compared to placebo, probiotics in pregnancy reduced anxiety symptoms (MD -0.99; 95% CI -1.80, -0.18); however, this advantage was not translated in a reduction in the proportion of participants scoring above an established cut-off for anxiety (pOR 0.65; 95% CI 0.23, 1.85). There were no differences between probiotics and control groups in global mental health scores at end of follow-up (MD 1.09; 95% CI -2.04, 4.22). Conclusion: There is limited but promising evidence about the effectiveness of probiotics during pregnancy to reduce anxiety symptoms and reduce the proportion of women scoring ABOVE a cut-off depression score. There is a lack of RCT evidence supporting prebiotics and synbiotics supplementation for similar purposes in the perinatal period. More research is needed before prebiotics, probiotics, and synbiotics are recommended to support maternal mental health and well-being in the perinatal period. Systematic Review Registration: PROSPERO, CRD42019137158.
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The Efficacy of Probiotics, Prebiotic Inulin-Type Fructans, and Synbiotics in Human Ulcerative Colitis: A Systematic Review and Meta-Analysis.
Astó, E, Méndez, I, Audivert, S, Farran-Codina, A, Espadaler, J
Nutrients. 2019;11(2)
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It is thought that ulcerative colitis (UC) may be caused by an excessive immune response to endogenous bacteria in genetically predisposed individuals, and therefore that manipulating of the gut flora may be of benefit. Microbial diversity and intestinal microbiota stability are lower in patients with inflammatory bowel disease (including UC), than in healthy people. This systematic review and metanalysis looked at clinical trials using probiotics, prebiotics and synbiotics (a combination of pro- and prebiotics) in UC. 18 papers were included, with a total of 1491 adult and 69 children. 16 of these were on probiotics, one on prebiotics and one on synbiotics. Outcomes considered in this systematic review were the effects on short chain fatty acids (SCFAs, metabolic end products of gut bacteria which have a beneficial effect on immune and gut health), inflammation levels, composition of faecal microbiota and UC remission. In trials on inactive UC patients, the faecal concentration of SCFAs did not differ significantly between the probiotic and placebo groups, whilst in trials with active UC patients, SCFAs significantly increased after probiotic supplementation. All studies reported a significant reduction in inflammation. Meta-analysis of studies which looked at induction/maintenance of remission by probiotics showed that this depends on a) the type of disease activity score used to assess remission, and b) the type of probiotics used, with bifidobacteria containing probiotics, VSL3 and Mutaflor showing benefits, but studies without bifidobacteria being no different from placebo. The authors conclude that bifidobacteria containing probiotics seem to be beneficial in terms of reaching remission in patients with UC, although there is insufficient information on necessary dose and duration of treatment. They note that there are only few studies on prebiotics and synbiotics and are calling for a standardisation of scales to assess remission.
Abstract
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13⁻2.15, p-value = 0.007, I² = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23⁻2.43, p-value = 0.002, I² = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
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Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis.
Jarde, A, Lewis-Mikhael, AM, Moayyedi, P, Stearns, JC, Collins, SM, Beyene, J, McDonald, SD
BMC pregnancy and childbirth. 2018;18(1):14
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It has been suggested that probiotics might help prevent premature birth, but two previous systematic reviews found possible increases in risk. The objective of this meta-analysis was to perform an up-to-date review of the risk of premature birth and other pregnancy outcomes in pregnant women taking probiotics or prebiotics. The authors pooled data from 27 studies, one using prebiotics and the rest probiotics. Taking probiotics or prebiotics during pregnancy did not change the risk of premature birth, or other pregnancy outcomes. The authors concluded that more studies are required to assess the safety and effects of taking probiotics and prebiotics during pregnancy.
Abstract
BACKGROUND Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit. It has been speculated that probiotics might help prevent preterm birth, but in two previous systematic reviews possible major increases in this risk have been suggested. Our objective was to perform a systematic review and meta-analysis of the risk of preterm birth and other adverse pregnancy outcomes in pregnant women taking probiotics, prebiotics or synbiotics. METHODS We searched six electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science's Core collection and BIOSIS Preview) up to September 2016 and contacted authors for additional data. We included randomized controlled trials in which women with a singleton pregnancy received a probiotic, prebiotic or synbiotic intervention. Two independent reviewers extracted data using a piloted form and assessed the risk of bias using the Cochrane risk of bias tool. We used random-effects meta-analyses to pool the results. RESULTS We identified 2574 publications, screened 1449 non-duplicate titles and abstracts and read 160 full text articles. The 49 publications that met our inclusion criteria represented 27 studies. No study used synbiotics, one used prebiotics and the rest used probiotics. Being randomized to take probiotics during pregnancy neither increased nor decreased the risk of preterm birth < 34 weeks (RR 1.03, 95% CI 0.29-3.64, I2 0%, 1017 women in 5 studies), preterm birth < 37 weeks (RR 1.08, 95% CI 0.71-1.63, I2 0%, 2484 women in 11 studies), or most of our secondary outcomes, including gestational diabetes mellitus. CONCLUSIONS We found no evidence that taking probiotics or prebiotics during pregnancy either increases or decreases the risk of preterm birth or other infant and maternal adverse pregnancy outcomes. TRIAL REGISTRATION We prospectively published the protocol for this study in the PROSPERO database ( CRD42016048129 ).
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Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review.
Ticinesi, A, Tana, C, Nouvenne, A, Prati, B, Lauretani, F, Meschi, T
Clinical interventions in aging. 2018;13:1497-1511
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Cognitive frailty is defined as the existence of both physical frailty and mild cognitive impairment, in the absence of a diagnosis of Alzheimer’s Disease or other form of dementia. As such, is considered to be the main pre-condition to developing dementia. Some recent studies have suggested an association between frailty and the gut microbiota, although little data exists on the links between the microbiome and cognitive health. This systematic review aimed to summarise the links made in the science between the gut microbiome and cognitive impairment and the effects of pre and pro-biotics on cognitive decline. 47 papers were identified (31 on animals and 16 on humans). Whilst a number of animal studies supported the link between cognitive impairment and the gut microbiota, there was a substantial lack of human data, preventing the researchers from formulating any clinical recommendations at this stage. Further research in human subjects is required to further our knowledge on the links between the gut microbiome and various forms of cognitive decline and dementia.
Abstract
Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of "gut-brain axis" has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer's disease) support the concept of a gut-brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.
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The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials.
Yeh, TL, Shih, PC, Liu, SJ, Lin, CH, Liu, JM, Lei, WT, Lin, CY
Drug design, development and therapy. 2018;12:217-230
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Influenza vaccination is widely used although concerns regarding its efficacy exist. Both prebiotics and probiotics have been shown to produce protective effects against influenza infection and may enhance the immune response to the vaccination, especially in the elderly. The aim of this systematic review and meta-analysis was to determine the effect of pre- and probiotics on immune response to the influenza vaccination. According to the existing literature, participants who took prebiotics or probiotics were found to have higher hemagglutination inhibition (HI) antibodies, meaning a reduced likelihood of the virus attaching to the host’s red blood cells. Based on these results, the authors conclude both pre- or probiotic supplementation may enhance immune response in three influenza strains. While these results are promising, larger controlled trials are warranted to confirm the effectiveness and establish best clinical practice for supplementation.
Abstract
BACKGROUND Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination. METHODS We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review. RESULTS Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, P=0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, P=0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, P=0.03). CONCLUSION Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted.
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Effect of Probiotics and Prebiotics on Immune Response to Influenza Vaccination in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Lei, WT, Shih, PC, Liu, SJ, Lin, CY, Yeh, TL
Nutrients. 2017;9(11)
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The influenza virus causes three to five million severe cases per year and currently the main way to minimise both morbidity and mortality is the influenza vaccine. Both prebiotics and probiotics have been shown to demonstrate protective effects against influenza infection. The aim of this systematic review and meta-analysis is to explore the effectiveness of probiotics and prebiotics on immune function in adults after an influenza vaccine. According to the existing literature, participants who took prebiotics or probiotics showed significant improvements in the immune response for three different strains of influenza vaccine. According to these results, the authors conclude that both pre- and pro- biotics can be used in adults prior to a seasonal influenza vaccine. Further large trials are required to both validate these findings as well as have a better understanding of the optimal dose and duration of supplementation.
Abstract
We conducted a meta-analysis to evaluate the effects of probiotics and prebiotics on the immune response to influenza vaccination in adults. We conducted a literature search of Pubmed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health (CINAHL), Airiti Library, and PerioPath Index to Taiwan Periodical Literature in Taiwan. Databases were searched from inception to July 2017. We used the Cochrane Review risk of bias assessment tool to assess randomized controlled trial (RCT) quality. A total of 20 RCTs comprising 1979 adults were included in our systematic review. Nine RCTs including 623 participants had sufficient data to be pooled in a meta-analysis. Participants who took probiotics or prebiotics showed significant improvements in the H1N1 strain seroprotection rate (with an odds ratio (OR) of 1.83 and a 95% confidence interval (CI) of 1.19-2.82, p = 0.006, I² = 0%), the H3N2 strain seroprotection rate (OR = 2.85, 95% CI = 1.59-5.10, p < 0.001, I² = 0%), and the B strain seroconversion rate (OR = 2.11, 95% CI = 1.38-3.21, p < 0.001, I² = 0%). This meta-analysis suggested that probiotics and prebiotics are effective in elevating immunogenicity by influencing seroconversion and seroprotection rates in adults inoculated with influenza vaccines.