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Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.
Gasmi, A, Noor, S, Tippairote, T, Dadar, M, Menzel, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;215:108409
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With the continuing spread of COVID-19 and lack of any approved treatments, this paper examines possible strategies for prevention. The data emerging so far highlights that individual health status plays a critical role in determining clinical severity of COVID-19 symptoms ranging from asymptomatic, mild, moderate, to death. Metabolic status, as determined by a patient’s diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors can therefore be considered preventative strategies to improve the severity of COVID-19 outcomes. Social distancing and personal hygiene are stated as the most effective strategies to prevent or slow spread of the disease. However individual health status, age and the presence of pre-existing comorbidities influences outcomes, as shown by global data highlighting a prevalence in older, males with metabolic conditions; hypertension in 23.7% patients and diabetes in 16.2% of patients. Older males appear more prone to infectious diseases with high pro-inflammatory immune responses and low adaptive immune responses than an older woman. Diet and healthy intestinal and respiratory tract microbiota may also influence immune system competence. Numerous micronutrients are essential for immunocompetence, particularly vitamin A, C, D, E, Bs, iron, selenium, and zinc. A balanced diet, high in colourful fruits and vegetables with a variation of prebiotic fibres, probiotics, and plant polyphenols and phytonutrients, help promote a healthy, diverse microbiota. Oral probiotics may also be beneficial to vulnerable individuals. Vitamin D supplementation is also proving helpful in prevention of acute respiratory tract infections. Other lifestyle factors such as smoking and exposure to environmental toxins should also be considered. Together these preventative measures may reduce personal risk of getting the disease.
Abstract
It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.
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Role of gut microbiota in cardiovascular diseases.
Novakovic, M, Rout, A, Kingsley, T, Kirchoff, R, Singh, A, Verma, V, Kant, R, Chaudhary, R
World journal of cardiology. 2020;12(4):110-122
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Cardiovascular disease (CVD) is the leading cause of death globally. CVD risk factors such as aging, obesity, dietary patterns and a sedentary lifestyle induce changes in the gut microbiota. The resulting dysbiosis is associated with intestinal inflammation leading to reduced integrity of the gut barrier. When this happens, certain components enter the circulation which may facilitate the development of CVD. Looking at the gut microbiota as a locus of intervention is therefore a novel and relevant avenue for future research. This article reviews the normal function and composition of the gut microbiome, the mechanisms leading to reduced gut barrier integrity (leaky gut syndrome), its link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. The alteration of the gut microbiome is a potential therapeutic target in managing CVD. However, further experiments are needed to see if the effects observed in animal studies can be translated to humans.
Abstract
The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.
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Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease.
Dimidi, E, Cox, SR, Rossi, M, Whelan, K
Nutrients. 2019;11(8)
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Fermented foods have grown in popularity due to their proposed health benefits but there is limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health. This review paper looks at non-dairy fermented foods which have been studied in at least one RCT: kefir, sauerkraut, natto, and sourdough bread. The health benefits are attributed to the high ratio of probiotic microorganisms, metabolites, or ability to convert compounds into active metabolites, as well as prebiotics and vitamins contained in these foods. Kimchi has the greatest evidence from epidemiological and case control studies investigating risk of gastric cancers. Different food composition of kimchi is shown to both increase and decrease risks, whilst it had no impact on H. pylori levels. There were no studies on kefir in functional bowel disorders however, it was shown to help lactose malabsorption and reduce H. pylori levels. A small RCT on Sauerkraut showed it reduced IBS severity in patients and increased in vitro activity of key liver and kidney detoxifying enzymes. There are small pockets of data that show that tempeh may influence gut microbiota in humans, and that natto may increase bifidobacterial and short-chain fatty acids in healthy volunteers. There are numerous limited cohort studies on miso and cancer risk but no studies on gastrointestinal conditions. Finally, sourdough was shown to reduce FODMAPS and be better tolerated in IBS patients, reducing bloating, nausea and discomfort. Overall, all the studies provide insufficient evidence on fermented foods and gastrointestinal health.
Abstract
Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.
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Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
Xie, C, Halegoua-DeMarzio, D
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an excessive accumulation of fat in the liver tissue, without excessive alcohol consumption, and appears to be related to metabolic syndrome. It is thought to have a prevalence of 25% globally and there are no pharmacological treatments available. This review discusses the connection between the gut microbiota (GM) and NAFLD. Various mechanisms by which the GM may be involved in the development of NAFLD are discussed. As probiotics and prebiotics can normalise GM and reverse dysbiosis their use may benefit patients with NAFLD. This has been confirmed in animal models. The authors review 26 randomised controlled trials (RCTs) of probiotics and/or prebiotics in the treatment of NAFLD which evaluate biochemical markers, as well as five meta-analyses, and found that overall there is strong evidence that probiotics and/or prebiotics can lower ALT and AST (markers of NAFLD), although results for other biochemical markers were mixed. They also reviewed RCTs assessing NAFLD by imaging and histological means, and again found benefits from probiotic and/or prebiotic supplementation.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.
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The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases.
Xu, H, Liu, M, Cao, J, Li, X, Fan, D, Xia, Y, Lu, X, Li, J, Ju, D, Zhao, H
Journal of immunology research. 2019;2019:7546047
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The human gut, or intestines, are populated with commensal bacteria which live in harmony with us and support various biological functions. The main role of the gut microbiota is to maintain the homeostasis of our immune system. It does this by maintaining the integrity of the intestinal lining and helping with digestive processes, production, and absorption of nutrients, and harvesting of immune cells. Our gut microbiome develops throughout infancy and confers benefits in adulthood and so any disruption to its development may impact on health. An imbalance between these helpful bacteria and more harmful pathogenic bacteria, which are also present in smaller amounts, is called dysbiosis and is a common factor in many autoimmune conditions. Autoimmune conditions are characterised by an over-active immune system where immune cells attack our own body. Imbalances in gut microbiota are also common, and diet is thought to be a key factor alongside other genetic and environmental factors. Evidence suggests that long-term dysbiosis may trigger autoimmune disease, amplify disease progression or both, as seen in studies on Arthritis, Lupus, Inflammatory bowel disease. The gut microbiota can be partially restored and supported with antimicrobial interventions, prebiotics, and selective probiotics. The review concludes that therapies targeting the gut microbiota may be effective in the future prevention or treatment of autoimmune diseases.
Abstract
The human gut-resident commensal microbiota is a unique ecosystem associated with various bodily functions, especially immunity. Gut microbiota dysbiosis plays a crucial role in autoimmune disease pathogenesis as well as in bowel-related diseases. However, the role of the gut microbiota, which causes or influences systemic immunity in autoimmune diseases, remains elusive. Aryl hydrocarbon receptor, a ligand-activated transcription factor, is a master moderator of host-microbiota interactions because it shapes the immune system and impacts host metabolism. In addition, treatment optimization while minimizing potential adverse effects in autoimmune diseases remains essential, and modulation of the gut microbiota constitutes a potential clinical therapy. Here, we present evidence linking gut microbiota dysbiosis with autoimmune mechanisms involved in disease development to identify future effective approaches based on the gut microbiota for preventing autoimmune diseases.
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Crosstalk between the microbiome and epigenome: messages from bugs.
Qin, Y, Wade, PA
Journal of biochemistry. 2018;163(2):105-112
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Trillions of microbes live symbiotically in and on an individual human being, most of them inside the digestive tract and communally known as the gut microbiome. The gut microbiome plays a vital role in the individual host’s health, not only by helping digest food and harvest energy, but also by regulating immune development and influencing gene expression. Diet and factors, such as infections and the use of antibiotics, can alter the balance of the microbiome and lead to various outcomes. This paper reviewed the current understanding of the ways in which the gut microbiome is capable of altering the host’s gene expression through microbial signals, including metabolites, bile acids, inflammation and altered composition. The studies highlighted in the paper show that gut microbes communicate both with local cells in the intestines and with more distant organs, such as the liver and the cardiovascular system. Through this communication, they can regulate the expression of immune cells, cancer cells, enzymes and inflammation-related molecules. The authors concluded that these interactions, or the crosstalk between the microbes and the host, demonstrate a crucial role of the gut microbiome in the host’s response to environmental signals. However, many of the mechanisms are still unclear, so further studies are needed to explain specific microbe-derived signals, affecting host gene expression, and to deepen our understanding of how lifestyle, health status and environmental exposures, such as antibiotics, regulate the microbiome and its influence.
Abstract
Mammals exist in a complicated symbiotic relationship with their gut microbiome, which is postulated to have broad impacts on host health and disease. As omics-based technologies have matured, the potential mechanisms by which the microbiome affects host physiology are being addressed. The gut microbiome, which provides environmental cues, can modify host cell responses to stimuli through alterations in the host epigenome and, ultimately, gene expression. Increasing evidence highlights microbial generation of bioactive compounds that impact the transcriptional machinery in host cells. Here, we review current understanding of the crosstalk between gut microbiota and the host epigenome, including DNA methylation, histone modification and non-coding RNAs. These studies are providing insights into how the host responds to microbial signalling and are predicted to provide information for the application of precision medicine.
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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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The microbiome and autoimmunity: a paradigm from the gut-liver axis.
Li, B, Selmi, C, Tang, R, Gershwin, ME, Ma, X
Cellular & molecular immunology. 2018;15(6):595-609
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The incidence of autoimmune and inflammatory diseases has been increasing worldwide. Changes in environmental factors, such as modern lifestyle, diet, antibiotics and hygiene are thought to play a critical role in the development of various autoimmune diseases. It is the mucosal microbial flora that is shaped by our environment and communicates with the innate and adaptive immune systems, and when disrupted, can lead to the loss of immune tolerance and dysregulated immune cells. This review paper provides an overview of the interactions between the intestinal microbiome and the immune system. It explains how these interactions affect host autoimmunity locally and systemically and sheds light on the molecular mechanisms, utilised by microbes that may contribute to systemic autoimmunity in genetically susceptible individuals. The links between the gut microbiome and various autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, as well as the gut-liver axis, involving intestinal microbiome and autoimmune liver diseases, are discussed in more detail.
Abstract
Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut-liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.
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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.