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The human gastrointestinal tract is colonised by a complex ecosystem of microorganisms. Intestinal bacteria are not only commensal, but they also undergo a synbiotic co-evolution along with their host. Beneficial intestinal bacteria have numerous and important functions, e.g., they produce various nutrients for their host, prevent infections caused by intestinal pathogens, and modulate a normal immunological response. Therefore, modification of the intestinal microbiota in order to achieve, restore, and maintain favourable balance in the ecosystem, and the activity of microorganisms present in the gastrointestinal tract is necessary for the improved health condition of the host. The introduction of probiotics, prebiotics, or synbiotics into human diet is favourable for the intestinal microbiota. They may be consumed in the form of raw vegetables and fruit, fermented pickles, or dairy products. Another source may be pharmaceutical formulas and functional food. This paper provides a review of available information and summarises the current knowledge on the effects of probiotics, prebiotics, and synbiotics on human health. The mechanism of beneficial action of those substances is discussed, and verified study results proving their efficacy in human nutrition are presented.

The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated with disease severity and restoration with probiotic administration in animal models and human patients has been associated with improvement of symptoms and disease progression. Characterizing the gut microbiota dysbiosis in different diseases and determining a causal relationship between the gut microbiota and disease can be beneficial in formulating therapeutic interventions for type 2 diabetes and associated complications. In this review, we present the most important findings regarding the role of the gut microbiota in type 2 diabetes and chronic complications as well as their underlying mechanisms.

Synbiotics are complex preparations of prebiotics that can be selectively utilized by live microorganisms to improve host health. Synbiotics are divided into complementary synbiotics, which consist of probiotics and prebiotics with independent functions, and synergistic synbiotics, which consist of prebiotics that are selectively used by gut microorganisms. Complementary synbiotics used in human clinical trials include Lactobacillus spp. and Bifidobacterium spp. as probiotics, and fructooligosaccharides, galactooligosaccharides, and inulin as prebiotics. Over the past five years, synbiotics have been most commonly used in patients with metabolic disorders, including obesity, and immune and gastrointestinal disorders. Several studies have observed alterations in the microbial community; however, these changes did not lead to significant improvements in disease outcomes or biochemical and hematological markers. The same synbiotics have been applied to individuals with different gut environments. As a result, even with the same synbiotics, there are non-responders who do not respond to the applied synbiotics due to the different intestinal environment for each individual. Therefore, to obtain meaningful results, applying different synbiotics depending on the individual is necessary. Synergistic synbiotics are one solution to circumvent this problem, as they combine elements that can effectively improve health, even in non-responders. This review aims to explain the concept of synbiotics, highlight recent human clinical trials, and explore the current state of research on synergistic synbiotics. Graphical abstract

Although non-alcoholic fatty liver disease (NAFLD) is the leading aetiology of liver disorders in the world, there is no proven treatment for NAFLD patients with normal or low BMI. The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI. In this randomised, double-blind, placebo-controlled, clinical trial, fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks. Both groups were advised to follow a healthy lifestyle. At the end of the study, hepatic steatosis and fibrosis reduced in both groups; however, the mean reduction was significantly greater in the synbiotic group rather than in the placebo group (P<0·001). Furthermore, serum levels of fasting blood sugar, TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group (P<0·05). Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI, at least partially through reduction in inflammatory indices. Further studies are needed to address the exact mechanism of action of these effects.

The purpose of this study was to investigate the beneficial effects of synbiotics on liver damage, intestinal health, and muscle loss, and their relevance in rats with chronic ethanol feeding. Thirty Wistar rats fed with a control liquid diet were divided into control and synbiotics groups, which were respectively provided with water or synbiotics solution (1.5 g/kg body weight/day) for 2 weeks. From the 3rd to 8th week, the control group was divided into a C group (control liquid diet + water) and an E group (ethanol liquid diet + water). The synbiotics group was separated in to three groups, SC, ASE, and PSE. The SC group was given a control liquid diet with synbiotics solution; the ASE group was given ethanol liquid diet with synbiotics solution, and the PSE group was given ethanol liquid diet and water. As the results, the E group exhibited liver damage, including increased AST and ALT activities, hepatic fatty changes, and higher CYP2E1 expression. Intestinal mRNA expressions of occludin and claudin-1 were significantly decreased and the plasma endotoxin level was significantly higher in the E group. In muscles, beclin-1 was significantly increased in the E group. Compared to the E group, the PSE and ASE groups had lower plasma ALT activities, hepatic fatty changes, and CYP2E1 expression. The PSE and ASE groups had significantly higher intestinal occludin and claudin-1 mRNA expressions and lower muscular beclin-1 expression when compared to the E group. In conclusion, synbiotics supplementation might reduce protein expression of muscle protein degradation biomarkers such as beclin-1 in rats with chronic ethanol feeding, which is speculated to be linked to the improvement of intestinal tight junction and the reduction of liver damage.

The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

Breastfeeding is natural and the optimal basis of infant nutrition and development, with many benefits for maternal health. Human milk is a dynamic fluid fulfilling an infant’s specific nutritional requirements and guiding the growth, developmental, and physiological processes of the infant. Human milk is considered unique in composition, and it is influenced by several factors, such as maternal diet and health, body composition, and geographic region. Human milk stands as a model for infant formula providing nutritional solutions for infants not able to receive enough mother’s milk. Infant formulas aim to mimic the composition and functionality of human milk by providing ingredients reflecting those of the latest human milk insights, such as oligosaccharides, bacteria, and bacterial metabolites. The objective of this narrative review is to discuss the most recent developments in infant formula with a special focus on human milk oligosaccharides and postbiotics.

In alignment with Hippocrates’ aphorisms “Let food be your medicine and medicine be your food” and “All diseases begin in the gut”, recent studies have suggested that healthy diets should include fermented foods to temporally enhance live microorganisms in our gut. As a result, consumers are now demanding this type of food and fermented food has gained popularity. However, certain sectors of population, such as those allergic to milk proteins, lactose intolerant and strict vegetarians, cannot consume dairy products. Therefore, a need has arisen in order to offer consumers an alternative to fermented dairy products by exploring new non-dairy matrices as probiotics carriers. Accordingly, this review aims to explore the benefits of different fermented non-dairy beverages (legume, cereal, pseudocereal, fruit and vegetable), as potential carriers of bioactive compounds (generated during the fermentation process), prebiotics and different probiotic bacteria, providing protection to ensure that their viability is in the range of 106–107 CFU/mL at the consumption time, in order that they reach the intestine in high amounts and improve human health through modulation of the gut microbiome.

Recent evidence suggests that probiotics, prebiotics and synbiotics may serve as important dietary components in the prevention (especially) and treatment of cardiovascular diseases (CVD), but the recommendations for their use are often based on brief reports and small clinical studies. This review evaluates the current literature on the correlation between CVD and probiotics, prebiotics and synbiotics. Although research on probiotics, prebiotics and synbiotics has grown exponentially in recent years, particularly regarding the effect of probiotics on CVD, their mechanisms have not been clearly defined. It has been proposed that probiotics lower cholesterol levels, and may protect against CVD, by increasing bile salt synthesis and bile acid deconjugation. Similar effects have also been observed for prebiotics and synbiotics; however, probiotics also appear to have anti-oxidative, anti-platelet and anti-inflammatory properties. Importantly, probiotics not only have demonstrated effects in vitro and in animal models, but also in humans, where supplementation with probiotics decreases the risk factors of CVD. In addition, the properties of commercial probiotics, prebiotics and synbiotics remain undetermined, and further experimental research is needed before these substances can be used in the prevention and treatment of CVD. In particular, well-designed clinical trials are required to determine the influence of probiotics on trimethylamine-N-oxide (TMAO), which is believed to be a marker of CVDs, and to clarify the long-term effects, and action, of probiotic, prebiotic and synbiotic supplementation in combination with drug therapy (for example, aspirin). However, while it cannot be unequivocally stated whether such supplementation yields benefits in the prevention and treatment of CVDs, it is important to note that clinical studies performed to date have not identified any side-effects to use.

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.