Impact of Prebiotics, Probiotics and Synbiotics on Components of the Metabolic Syndrome

Research Article

Ann Nutr Disord & Ther. 2014;1(2): 1009.

Impact of Prebiotics, Probiotics and Synbiotics on Components of the Metabolic Syndrome

Scavuzzi BM1, Henrique FC2, Miglioranza LHS3, Simão ANC4 and Dichi I5*

1Department of Health Sciences, University of Londrina, Brazil

2Department of Food Science, University of Londrina, Brazil

3Department of Food Science and Technology, University of Londrina, Brazil

4Department of Pathology, University of Londrina, Brazil

5Departament of Internal Medicine, University of Londrina, Brazil

*Corresponding author: Dichi I, Department of Internal Medicine, University of Londrina, Rua Robert Koch n. 60, Londrina, Paraná, Brazil

Received: August 08, 2014; Accepted: September 02, 2014; Published: September 03, 2014

Abstract

Changes in eating habits are undoubtedly the most important nonpharmacologic factor for the prevention and treatment of risk factors of metabolic syndrome and, therefore, nutritional therapies have been researched. The consumption of prebiotics, probiotics and synbiotics gained recognition from the scientific community due to the promising effects on health and well-documented history of safe use. Thus, this article presents a review of scientific studies investigating clinical responses of patients treated with prebiotics, probiotic or symbiotic, and raises the key issues to be considered by scientists in the search of dietary alternatives for patients suffering from metabolic syndrome.

Keywords: Dysbiosis; Obesity; Dyslipidemia; Insulin resistance; Inflammation

Abbreviations

ALA: Alpha Linolenic Acid; B: Bifidobacterium; BMI: Body Mass Index; BP: Blood Pressure; CG: Chitin-Glucan; CRP: C-Reactive Protein; DB: Double-Blind; DBP: Diastolic Blood Pressure; FOS: Fructo Oligosaccharides; GLP-1: Glucagon-Like Peptide 1; HDL-C: HDL Cholesterol; HOMA: Homeostasis Model Assessment; hs- CRP: high-sensitive C-Reactive Protein; IL: Interleukin; IR: Insulin Resistance; L: Lactobacillus; LDL-C: LDL Cholesterol; Lp(a): Lipoprotein A; LPS: Plasma Lipopolysaccharide; MetS: Metabolic Syndrome; OFS: Oligofructose; OGTT: Oral Glucose Tolerance Test; OxLDL: Oxidized Low-Density Lipoprotein; PYY: Peptide YY; RCT: Randomized Control Trial; RCOT: Randomized Cross- Over Trial; RPCT: Randomized Placebo Controlled Trial; SBP: Systolic Blood Pressure; SCFA: Short-Chain Fatty Acids; T2D: Type 2 Diabetes Mellitus; TAC: Plasma Total Antioxidant Capacity; TC: Total Cholesterol; TG: Triglycerides; TNF-a: Tumor Necrosis Factoralpha; VLDL-C: VLDL Cholesterol.

Introduction

Metabolic syndrome is a complex disorder represented by a cluster of cardiovascular risk factors associated with central fat deposition, abnormal plasma lipid levels, elevated blood pressure insulin resistance and intestinal dysbiosis [1-4]. Changes in eating habits are undoubtedly the most important non-pharmacological factor for the prevention and treatment of the risk factors of the MetS and various nutritional therapies have been researched [5,6]. Among the nutritional therapies to prevent MetS risk factors, the scientific literature has pointed to the consumption of probiotic, prebiotic and symbiotic products.

The gastrointestinal tract is composed of several connected organs that are involved in nutrient conversion and providing energy sources from the food absorbed. This complex system has a well-known anatomical architecture that is approximately 7m long, comprising 300m2 surface area in adults. The human large intestine has a bacterial flora with total numbers of 1014 cells, (ten times the number of the cells of the human body) more than 1000 species and a biomass superior 1Kg [7,8].

From the mouth to the colon, there is a complex micro biota consisted of facultative and strict anaerobes, including streptococci, bacteroides, lactobacilli and yeasts [9,10]. The micro biome comprises nearly two million genes, being the collective bacterial genome vastly greater than the human genome. The advent of high-through put methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the microbial constituents of the human gut as never before and are now enabling comparisons to be made between health and various disease states [11].

Currently, it has also been recognized that this dynamic yet stable ecosystem plays a role in conditions such as obesity and diabetes as well as in general well-being, from infancy to ageing [7,12-15]. The literature has demonstrated different gut microbial composition between non-diabetics and adults with T2D, and lean and obese individuals [7,16] and suggested that gut microbial composition may affect the metabolism and energy storage [17]. The main functions of the gut micro biota are ascribed into three categories: metabolic, protective and trophic [18].

A consensus definition of the term “probiotics” was adopted after a joint Food and Agricultural Organization of the United Nations and World Health Organization expert consultation. In October 2001, the Organizations experts defined probiotics as “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host.” The original idea of the probiotics concept (that can be translated in ‘probiotics effects’), was defined as: ‘the selective stimulation of growth and/or activity (ies) of one or a limited number of microbial genus (era)/species in the gut micro biota that confer(s) health benefits to the host.’ When probiotics and prebiotics are used in combination, they are known as synbiotics [19,20].

The consumption of prebiotics, probiotics and synbiotics has gained recognition from the scientific community due to the promising health effects and well documented history of safe use. Thus, the present review gathers recent and relevant literature found in at least 130 Databases included in the virtual library “Portal CAPES Consortia” (Higher Education Personnel Improvement Coordination –Brazil) published from 1994 to 2014, involving the consumption of prebiotics, probiotics and synbiotics and the components of the MS. There were no restriction groups, but searches have focused on texts written in English.

Probiotics


The modulation of the intestinal microbiota is one of the potential beneficial health effects of probiotics, and numerous research studies have documented that probiotics can impact the gut microbiota [21]. The mechanisms and efficiency of the probiotic effect depend primarily on the interactions between the probiotic microorganisms and either the microbiota of the host or the immunocompetent cells of the intestinal mucosa [22,23].

Dysbiosis of the intestinal microbiota has been associated with a growing number of diseases. Some data on the MetS suggest that changes in gut microbiome composition may play a role in the disorder. Recently, fecal microbiota transplant from non-diabetic donors infused into the duodenum of patients with the MetS improved their insulin sensitivity, highlighting the broad potential of this intervention [24]. Since modulation of the composition of intestinal microbiota by probiotics was demonstrated to be possible, this intervention has the potential to counterbalance intestinal Dysbiosis and thus restore health [22].

Probiotics may play a beneficial role in several medical conditions, including diarrhea, gastroenteritis, irritable bowel syndrome, inflammatory bowel disease, cancer, depressed immune function, infant allergies, failure-to-thrive, hyperlipidemia, hepatic diseases, Helicobacter pylori infections, and others [25].

The effects of probiotics are mediated by the role of probiotic bacteria in normalization of intestinal microbiota composition, immunomodulation, and maintenance of gut barrier function. With advancing knowledge of how probiotics interact with the gut microbiome, there is an increasing interest in exploring the effect of probiotics on specific elements of the MetS in humans [26].

Several strains of probiotics improve metabolic parameters such as hypertension, abnormal plasma lipid levels, obesity, inflammation and glucose homeostasis disorders [15,27-30]. The important criteria that have been put forward by FAO/WHO in the selection of food probiotics include identification of strains using state-ofthe- art techniques, ability to tolerate gastric juice and bile, maintain stability and, most importantly, prove to be safe and beneficial to the consumer. A number of genera of bacteria are used as probiotics, including Lactobacillus, Bifidobacterium, Pediococcus, Leuconostoc and Enterococcus [31]. Amongst probiotics, L. acidophilus NCFM / La5, L. casei subsp. casei, L. gasseri SBT2055, L. helveticus, L. plantarum 299v, L. rhamnosus GG, L. reuteri NCIMB, B. lactis Bb12 and others, have human health efficacy data with desirable properties and well-documented clinical effects on parameters of MetS [30,32- 36].

The physiological effects of probiotics are highly strain-dependent. The variations in outcomes between different studies appear to be due to choice of probiotic strain, route of administration and length of study. Human studies considering probiotics and components of the MetS are still under consideration.

Probiotics and body weight

Numerous studies of the human gut microbiome found evidence of core differences between lean and obese individuals, reduced diversity of the microbiota in obese individuals and suggested that gut microbial composition may affect the metabolism and fat storage [17,37-39],

Additionally, studies have recognized that the composition of the gut microbiota has an impact on energy homeostasis and suggested that probiotics have a positive impact on weight loss. However, it is important to mention that the physiological effects of probiotics are highly strain-dependent. Million et al., 2012, conducted a comparative meta-analysis of studies considering the effect of species of Lactobacillus on body weight of humans and animals. The authors found that the species fermentum and ingluviei were associated with weight gain in animals, plantarum was associated with weight loss in animals and gasseri was associated with weight reduction in animals and humans [40].

Five studies considering the impact of probiotics on body weight were considered for this review. All the studies documented improvements in this MetS parameter after probiotic consumption (Table 1). The mechanisms involved in the reported body weight reduction are not clear, but studies point out to the reduction of adipocyte size [41,42], inhibition of adiposeness [43] and the suppression of energy intake [44].

Table 1: Human studies considering probiotics and body weight.

Probiotics and blood lipids

Guo et al, 2011 conducted a meta-analysis of randomized controlled trials to evaluate the effects of probiotics on blood lipids. The authors found evidence that probiotics decreases plasma LDL and total cholesterol in subjects with normal, borderline high and high cholesterol levels [46]. Similarly, nine out of the twelve studies in this review documented significant improvements in blood lipids after probiotic consumption (Table 2).

Table 2: Human studies considering probiotics and blood lipids.

Although the mechanisms involved in the cholesterol-lowering effect are not clearly understood, it is accepted that the inhibition of intestinal cholesterol absorption, suppression of bile acid reabsorption [47,48] and production of short-chain fatty acids, which reduce cholesterol synthesis, are involved [49].

Probiotics and glucose homeostasis

Firouzi et al, 2013 conducted a review of studies in animals and humans that considered the impact of probiotics on parameters of glucose homeostasis. The authors found that 16 out of 17 studies in animals, and three out of four studies in humans, had documented significant improvements in at least one glucose homeostasis related parameter [59]. Similarly, in the present review, three out of five studies documented improvements in this MetS parameter after probiotic consumption (Table 3). Currently, it is known that the glucose homeostasis is negatively affected by a low grade chronic inflammatory state promoted by lipopolysaccharide binding to CD14 toll-like receptor-4 [60,61].

Table 3: Human studies considering probiotics and glucose homeostasis.

Probiotics and inflammatory markers

The pathways involved in the reduction of inflammation markers are still under investigation. However, it is possible that increase of glucagon-like peptide-2 production and a resulting improvement of gut permeability [63], decrease of proinflammatory cytokines [64], a toll-like receptor 9 signaling mediation [65] are involved.

One third of the investigations included in this review documented improvements in this MetS parameter after probiotic consumption (Table 4).

Table 4: Human studies considering probiotics and inflammatory markers.

Probiotics and blood pressure

In a recent systematic review and meta-analysis of randomized controlled trials, Khalesi et al, 2014 concluded that probiotics moderately reduce blood pressure. The authors found evidence that BP reduction is greater when the intervention has a duration superior to eight weeks, when daily dose of probiotic consumption is greater than (or equal to) 1011 colony-forming units, and among individuals with elevated BP. The study also suggests a greater BP-lowering effect when multiple species of probiotics are consumed [66]. In the present review, five out of seven studies documented improvements in this MetS parameter after probiotic consumption (Table 5).

Table 5: Human studies considering probiotics and blood pressure..

The blood-pressure lowering ability of some probiotics has been related to the release of bioactive peptides that have an Angiotensin- Converting Enzyme (ACE) inhibitor effect [67]. The blood-pressure decrease may also be a result of the reduction of blood lipids [68] and body weight [69].

Safety considerations

Given the growing reports of health benefits of probiotics and the resulting widespread use of these products, it is important to be aware that safety data, particularly long-term safety. Studies concerning safety of these products are still very limited and there are no established guidelines for this evaluation. Some probiotics have been used for thousands of years without being associated to undesirable effects. However, the health effects are strain-dependent and should not be generalized without prior confirmation. Probiotics contain live organisms and although very rare, may cause infections. Therefore, there are safety issues particularly amongst individuals with compromised immune systems. Lactobacilli strains, for example, have been associated with rare cases of bacterial sepsis in debilitated individuals, despite of the long history of safe use. For the general population, probiotics appear to be safe and side effects, if present, tend to be mild and digestive, such as gas or bloating [19,76,77]. Contrarily, some probiotic species have demonstrated beneficial effect in decreasing the symptoms of bloating in patients with irritable bowel syndrome [78].

Another area of concern is that probiotics are commonly commercialized as foods or dietary supplements and, therefore, there is no requirement to demonstrate the purity of these products [76]. Reports of mislabeled number of live organisms and identification of strains indicate a need for recognized regulations concerning labeling issues and claims, to ensure safety of these products [79, 80].

Prebiotics

Prebiotics are selectively fermented dietary fibers that are found naturally in plants such as asparagus, bananas, berries, chicory, garlic and onions and that promote the growth of beneficial microorganisms such as Lactobacilli and Bifidobacteria in the intestine. Some examples of prebiotics include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides and lactulose. The consumption of nutrients with prebiotics properties is associated with changes in the gut microbiota and improvements in metabolic parameters related to obesity, inflammation, glucose homeostasis disorders and abnormal plasma lipid levels [85-89,97-121]. Additionally, increased satiety has been associated to the intake of prebiotics, which may contribute to weight management [85-87].

Consumption of prebiotics appears to be effective in the modulation of the components of the MetS. Yacon roots, the most abundant know source of fructooligosaccharides [88], for example, have been related to antiglycemic, hypolipidemic, laxative and slimming effects [89-91].

The exact mechanisms by which prebiotics contribute to the improvement of metabolic parameters are not completely elucidated. The hypotriglyceridemic action seems to be associated to decreased expression of the liver lipogenic pathway [92]. The antilipemic effects have been associated to decreased cholesterol absorption / increased excretion of cholesterol through feces and by the production of shortchain fatty acids such as acetate, butyrate and propionate produced by intestinal micro flora fermentation [93]. The antiobesity and antidiabetic effects are probably related to the binding of SCFA to G-protein coupled receptors and subsequent increase of glucagonlike peptide 1 and peptide YY [94,95]. The antihypertensive effects may be a result of the lowering of cholesterol attributed to the prebiotics [96].

Seven studies considering the impact of probiotics on body weight were included in this review and six of them documented improvements in this MetS parameter after probiotic consumption (Table 6). However, in a systematic review of randomized controlled trials, Kellow et al, concluded that there is insufficient evidence at present to recommend dietary prebiotics for reducing energy intake and body weight. The authors also noted that studies with a duration superior to 12 weeks were more likely to observe reduction in body weight [122].

Table 6: Human studies considering prebiotics and body weight, energy intake or satiety..

Studies measuring blood lipids after prebiotics consumption have yielded promising results. Thirteen studies considered the impact of prebiotics on lipids levels in this review, and nine documented significant improvements in this MetS parameter after probiotic consumption (Table 7).

Table 7: Human studies considering prebiotics and blood lipids.

Prebiotics also seem to have positive effect on glucose metabolism. In the systematic review of randomized controlled trials conducted by Kellow et al, the authors found that studies generally supported significant reduction in postprandial glucose and insulin concentrations in healthy and overweight individuals after consumption of prebiotics [122]. Similarly, in the present review,most studies documented improvements these parameters of glucose homeostasis after prebiotics consumption (Table 8).

Table 8: Human studies considering prebiotics and glucose homeostasis.

Although there is not enough evidence to recommend the use of prebiotics to improve inflammatory markers, measures of antioxidant capacity and blood pressure, all of the studies considered in this review reported improvements for these markers (Tables 9 and 10). Therefore, further studies and more detailed clinical trials are needed to support these clinical findings.

Table 9: Human studies considering prebiotics and inflammatory or oxidative stress markers.

Table 10: Human studies considering prebiotics and blood pressure.

Synbiotics

Synbiotics are defined as ‘a mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract’ [123]. Studies on the effects of synbiotics on metabolic health still are limited. It is worth mentioning that the health effect will likely depend on the symbiotic combination. Therefore, although synbiotics seem promising for the modulation of the gut microbiota composition, the effects remain to be confirmed by human trials, once very few human studies considering synbiotics and components of the MetS have been published (Tables 11-15).

Studies considering the impact of symbiotic supplementation on body composition or energy intake have yielded mixed results. Only two out of the five studies considered for this review documented improvements of these markers (Table 11).

Table 11: Human studies considering synbiotics and body weight, energy intake or satiety.

Only one study considered for this review evaluated changes in blood pressure after consumption of synbiotics. A significant decrease in systolic blood pressure was documented (Table 12).

Table 12: Human studies considering synbiotics and blood pressure.

Similarly to probiotics and prebiotics, studies generally support significant improvement on blood lipid profile following synbiotics supplementation. In this review, six out of seven studies documented improvement of at least one blood lipid (Table 13).

Table 13: Human studies considering synbiotics and blood lipids.

Although the number of studies is still very limited, symbiotic consumption seems to have a positive effect on glucose homeostasis. Two out of three studies considered for this review documented improvements in this parameter after the consumption of dietary synbiotics (Table 14).

Table 14: Human studies considering synbiotics and glucose homeostasis.

Even though there is not enough evidence to recommend the use of prebiotics to improve inflammatory markers, most studies considered for this review documented improvements in at least one inflammatory marker after the consumption synbiotics (Table 15).

Table 15: Human studies considering synbiotics and inflammatory or oxidative stress markers.

Conclusion

A diet rich in prebiotics, probiotics and synbiotics might confer numerous health benefits to the host possibly due to positive gut microbiota modulation. However, further studies should provide reliable mechanistic, safety and clinical evidence before recommending prebiotics, probiotics and synbiotics to individuals with the MetS.

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Citation: Scavuzzi BM, Henrique FC, Miglioranza LHS, Simão ANC and Dichi I. Impact of Prebiotics, Probiotics and Synbiotics on Components of the Metabolic Syndrome. Ann Nutr Disord & Ther. 2014;1(2): 1009. ISSN:2381-8891