Scavuzzi BM; Henrique FC; Miglioranza LHS; Simão ANC; Dichi I

Research Article

Ann Nutr Disord & Ther. 2014;1(2): 1010.

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.

Study
Population
Conclusion
Reference���

A DB, RPCT to investigate the impact of a L. rhamnosus CGMCC1.3724 (LPR)
supplementation on weight loss and maintenance.
125 obese adults (48 male and 77 female) aged 18-55 years.
LPR supplementation can accentuate body-weight loss and seems to
help obese women to maintain healthy body weight.
[27]

A DB, randomized, prospective study to evaluate the impact of
perinatal probiotic intervention (L. rhamnosus GG - ATCC 53103) on childhood growth patterns and the development of overweight during a 10-year follow-up.
159 women before delivery and 113 children were measured at the ages of 3, 6, 12 and 24 months and 4, 7 and 10 years.
Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life.
[29]

A multicenter, DB, RPCT to evaluate the effects of the probiotic L. gasseri SBT2055 (LG2055) - originated from the human gut - on
abdominal adiposity, body weight and other body measures.
87 healthy adults (59 men/ 28 women) with BMI of 24.2-30.7?kg/m² and abdominal visceral fat area (81.2-78.5?cm²).
LG2055 consumption promoted a significant reduction in abdominal adiposity, BMI, waist and hip circumference.
[33]

A DB, RPCT parallel pilot study to evaluate the effects of a hypocaloric diet supplemented with a probiotic cheese containing L. plantarum strain TENSIA on obese hypertensive patients.
25 obese hypertensive patients.
The hypocaloric diet supplemented with a probiotic cheese helped to reduce BMI.
[45]

A DB, RPCT to assess the beneficial effects on MetS of functional yogurt

NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea)
supplemented with Streptococcus thermophilus,� L. acidophilus, B. infantis.
101 healthy adults� (70 women and 31 men), 20-65
years.
The functional yogurt NY-YP901 with probiotics reduced body weight and BMI.
[50]



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.

Study
Population
Conclusion
Reference���

A DB, RPCT to investigate the effect of L. salivarius Ls-33 on a series of biomarkers related to inflammation and the MetS.
50 obese adolescents (28 female and 22 male), 12-15 years.
No evidence of any beneficial effect on lipid profile.
[13]

A DB, RPCT to assess the
cholesterol-lowering clinical efficacy and safety of microencapsulated L. reuteri NCIMB 30242 supplemented in a yogurt formulation.
114 healthy hypercholesterolaemic adult men and women, 18-74 years.
Microencapsulate L. reuteri yoghurt consumption decreased LDL-C, TC and non-HDL-C.
[28]

A DB, RCT to investigate the effects of probiotic (L. acidophilus La5 and B. lactis Bb12) and conventional yogurt on the lipid profile.
60 adults (23 men and 37 women) with T2D and LDL-C > 2.6 mmol/L, 30-60 years.
Probiotic yogurt improved TC and LDL-cholesterol.
[35]

A RPCT to verify and compare the effects of probiotic (L. casei subsp. casei) and conventional yoghurt on the plasma lipid profile.
33 healthy, non-smoking, normocholesterolemic women, 22-29 years.
The total/HDL and LDL/HDL-C ratios improved in both probiotic and conventional yogurt intake.
[36]

A DB, RPCT to assess the beneficial effects on MetS of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with Streptococcus thermophilus,� L. acidophilus, B. infantis.
101 healthy adults� (70 women and 31 men), 20-65
years.
The functional yogurt NY-YP901 with probiotics reduced LDL-C.
[50]

A triple blind, randomized study to test the effect of probiotic (L. acidophilus La5 and B. lactis Bb12) and conventional yogurt on the lipid profile.
90 women, 19-49 years.
Decrease in cholesterol, increase in HDL-C, decrease in total:HDL-C ratio) were observed in both yogurt groups.
[51]

A single-blind, RCOT to compare the effect of consuming probiotic yogurt (L. acidophilus and B. lactis) with that of ordinary yogurt on serum cholesterol level.
14 adults (10 men and 4 women) 40-64 years with mild to moderate hypercholesterolemia.
Cholesterol-lowering effect.
[52]

A single-blind, RPCT to investigate the effect of probiotic capsules (L. acidophilus DDS-1 and B. longum UABL-14) on plasma lipid concentrations.
55 normocholesterolemic adults (33 premenopausal women and 22 men), 18-36 years.
No evidence of any beneficial effect on plasma lipids.
[53]

A single-center, DB, placebo-controlled study to assess the effects of PCC� L. fermentum on LDL cholesterol and other lipid fractions.
44 adults (16 men and 28 women) 30-75 years.
No major effect of Lactobacillus fermentum on serum lipids.
[54]

A single-blind, parallel group study to demonstrate the effect of milk fermented by B. longum strain BL1 on blood lipids.
32 healthy males with serum TC
levels within the range of 220 to 280 mg/dl. 35-52 years.
B. longum yogurt lowered serum TC, especially in subjects with moderate hypercholesterolemia.
[55]

A randomized, DB, placebo-and compliance-controlled, parallel study to investigate the effect of a probiotic milk product containing the culture CAUSIDO� and of two alternative products on risk factors for cardiovascular disease.
70 healthy, weight-stable, overweight and obese adults (20 men and 50 women) 18-55 years.
CAUSIDO� culture reduced LDL-cholesterol.
[56]



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.

Study
Population
Conclusion
Reference���

A RPCT to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS and other parameters related to cardiovascular risk.
24 postmenopausal women with MetS, 60-75 years.
L. plantarum consumption decreased glucose levels.
[15]

A DB, RPCT to investigate the effects of the widely applied probiotic strain L. acidophilus NCFM on insulin sensitivity and the systemic inflammatory response.
45 men with T2D, impaired or normal glucose tolerance.
L. acidophilus NCFM intake preserved insulin sensitivity compared with placebo.
[32]

A randomized, prospective, parallel-group intervention study to investigate whether supplementation of probiotics (L. rhamnosus GG, ATCC 53 103 and B. lactis Bb12) with dietary counselling affects glucose metabolism.
256 pregnant women (mean age of 30 years).
Combined dietary counselling and probiotics intervention yielded improved glucose metabolism and insulin sensitivity.
[57]

A DB, RPCT to investigate the effect of a probiotic capsule (L. salivarius UCC118) on maternal fasting glucose.
175 pregnant women with BMI from 30.0 - 39.9 kg/m2. Age > 18 years.
No influence on maternal fasting glucose, metabolic profile or pregnancy outcomes.
[62]



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.




  
    Study
    Population
    Conclusion
    Reference��� 
  
  
    A DB, RPCT to    investigate the effect of L. salivarius Ls-33 on a series of biomarkers    related to inflammation and the MetS.
    50 obese adolescents    (28 female and 22 male), 12-15 years.
       
    No evidence of any    beneficial effect on inflammatory markers.
    [13]
  
  
    A RPCT to evaluate    the influence of fermented milk with L. plantarum in the classical parameters    related to MetS and other parameters related to cardiovascular risk.
    24 postmenopausal    women with MetS, 60-75 years.
    L. plantarum    consumption decreased homocysteine levels.
    [15]
       
  
  
    A DB, RPCT to    investigate the effects of the widely applied probiotic strain L. acidophilus    NCFM on insulin sensitivity and the systemic inflammatory response.
    45 men with T2D,    impaired or normal glucose tolerance.
    L. acidophilus NCFM    intake did not affect the systemic inflammatory response.
    [32]



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..

Study
Population
Conclusion
Reference���

A DB, RPCT parallel pilot study to evaluate the effects of a hypocaloric diet supplemented with a probiotic cheese on obese hypertensive patients.
25 obese hypertensive patients.
The hypocaloric diet supplemented with a probiotic cheese helped to reduce arterial BP.
[45]

A DB, RPCT parallel group study to evaluate the effects of two doses of lactotripeptides (from Lactobacillus helveticus LBK-16H-fermented milk products) on 24-h ambulatory blood pressure and lipidomics profiles in mildly hypertensive subjects.
89 mildly hypertensive subjects.
Mild, but not significant decrease of blood pressure.
[70]

A DB, RPCT to study the antihypertensive effect of Lactobacillus helveticus FM in prehypertensive and borderline hypertensive subjects.
94 prehypertensive and borderline hypertensive subjects.
No significant antihypertensive effect.
[71]

A DB, RPCT to evaluate the effect and safety of powdered fermented milk with Lactobacillus helveticus CM4 on subjects with high-normal blood pressure or mild hypertension.
40 subjects with high-normal blood pressure and 40 subjects with mild hypertension
Decrease in blood pressure.
[72]

A RCOT to evaluate the effect on BP in subjects with mild hypertension of a new sour milk containing tripeptides (from Lactobacillus helveticus).
60 subjects with mild hypertension (36 men, 24 women).
Modest decrease in blood pressure.
[73]

A DB, RPCT to assess the effect of sour milk, containing two tripeptides (valine-proline-proline and isoleucine-proline-proline), on blood pressure (BP)
6 borderline hypertensive men, 23-59 years.
Decrease in blood pressure.
[74]

A DB, RPCT to evaluate the long-term blood pressure-lowering effect of milk fermented by Lactobacillus helveticus LBK-16H in hypertensive subjects.
39 hypertensive patients.
Decrease in blood pressure.
[75]



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..

Study
Population
Conclusion
Reference

A single-blinded, crossover, RPCT, pilot study to study the effects of oligofructose on satiety and energy intake in humans.
5 men/5 women, 21-39 years, BMI 18.5-27.4 kg/m2.
Increased satiety following breakfast and dinner, reduced hunger and prospective food consumption following dinner. Total energy intake per day is 5% lower during oligofructose than in the placebo period.
[85]

A two-week DB, parallel, RPCT to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal.
5 healthy men and women (10 subjects).
Increase in plasma concentrations of GLP-1 and PYY.
[86]

A 12-week, DB, RPCT to examine the effects of oligofructose supplementation on body weight and satiety hormone concentrations in overweight and obese adults.
39 healthy subjects (32 women/7 men).
Significantly higher weight loss in oligofructose group than the control group.
[87]

A 120-day, DB, RPCT to verify the effects of yacon (rich in FOS) syrup on obesity and IR in humans.
35 pre-menopausal women, 31-49 years, with no menopausal disorders, obesity with mild dyslipidemia.
Daily intake of yacon syrup produced a significant decrease in body weight, waist circumference and BMI.
[89]

A DB, parallel, RPCT to determine variations on fecal SCFA concentration in obese women treated with inulin-type fructans and to explore associations between Bifidobacterium species, SCFA and host biological markers of metabolism.
30 obese women
Total SCFA, acetate and propionate, which positively correlated with BMI.
�[97]

A DB, RCOT to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human
31 healthy subjects (10 men/21 women).
Energy intake was significantly reduced with 16 g/d oligofructose compared with 10 g/d, possibly supported by higher GLP-1 and PYY concentrations.
[105]

A DB, RCOT to test the effect of FOS, beta-glucan, or a combination thereof on appetite ratings and food intake over 2 consecutive days.
21 healthy subjects (16 women/5 men).
The addition of beta-glucan, FOS, or a combination thereof did not affect appetite ratings or food intake.
[107]



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.

Study
Population
Conclusion
Reference

A 6-week, DB, RPCT to evaluate the efficacy of chitin-glucan, alone and in combination with a potentially anti-inflammatory olive oil extract, for reducing OxLDL in subjects with borderline to high LDL-C levels.
130 subjects aged 21-70 years, BMI of 18.5–34.9kg/m2, fasting serum levels of LDL-C 3.37–4.92mmol/l.
CG (4.5g/day) reduced OxLDL. CG was associated with lower LDL-C levels in the� 1.5g/day group.
[98]

A 12-week DB, crossover, RPCT to study the effect of a galactooligosaccharide mixture on markers of MetS, gut microbiota, and immune function.
45 overweight adults with =3 risk factors associated with MetS.
Decrease in plasma TC, TG, and TC/HDL-C ratio.
[102]

A 3-month, RCT to evaluate the efficacy of a partial meal replacement with inulin on weight reduction, blood lipids and micronutrients intake in obese Mexican women.
144 women aged 18–50 years with BMI=25kg/m2
Reduced TG and improved intake of micronutrients during caloric restriction.
[103]

A one-month, DB, RCT to evaluate the response of the cardiovascular risk profile in obese patients after inclusion in the diet of an ALA, FOS and inulin enriched-cookie.
36 obese subjects (BMI >30).
Improved TC and LDL-C levels in obese men.
[104]

A DB, RCOT to evaluate the effects of the daily consumption of inulin-enriched pasta on lipid and glucose metabolism as well as on gastrointestinal motility in young healthy subjects.
22 healthy men.
Improved lipidic profile (HDL-C, TC/HDL-C ratio and TG) in healthy young subjects.
[106]

A 3-week DB, crossover, RPCT study to asses the effects of a moderately high-carbohydrate, low-fat diet plus an oral placebo or 10 g high-performance inulin/day on hepatic lipogenesis and plasma triacylglycerol concentrations.
8 healthy subjects.
Decreased plasma TG concentrations and hepatic lipogenesis.
[113]

A 3-week, DB, RCOT to assess the effects of dietary inulin on serum lipids, blood glucose and the gastrointestinal environment in hypercholesterolemic men.
12 hypercholesterolemic men.
Daily intake of 20 g of inulin significantly reduced serum TG.
[115]

A DB crossover design to study the effects of the chronic ingestion of FOS on plasma lipid and glucose concentrations, hepatic glucose production and IR in T2D.
10 subjects with T2D (6 men/4 women)
4 weeks of 20 g/d of FOS had no effect on lipid metabolism in T2D subjects.
[116]

A single-blind, RCOT to study the effects of FOS on blood glucose, serum lipids, and serum acetate in patients with T2D.
20 patients with T2D (9 men /11 postmenopausal women).
No major effect on serum lipids.
[117]

A DB, RCOT to study the effect of consuming three servings per day of inulin-containing foods, compared to similar foods without inulin, on serum lipid profiles among hypercholesterolemic men and women.
21 subjects with baseline LDL-C of 3.36-5.17 mmol/L.
No differences were found between any of the lipid variables when the values at the end of the inulin and control periods were compared.
[118]

A RCOT to investigate the effect of a breakfast cereal containing inulin on blood lipids and colonic ecosystem in normolipidemic young men.
12 healthy men.
Plasma TC and TG significantly decreased.
[119]

A Latin square, DB, RCOT to study the effect of the intake of 15 g non-digestible oligosaccharides per day on various parameters of large-bowel function, as well as on blood lipid concentrations and glucose absorption in man.
12 healthy men.
The consumption of 15 g non-digestible oligosaccharides does not seem to alter blood lipid concentrations in young healthy adults.
[120]



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).

Study	Population	Conclusion	Reference��
A DB, RPCT to investigate the impact of a L. rhamnosus CGMCC1.3724 (LPR) supplementation on weight loss and maintenance.	125 obese adults (48 male and 77 female) aged 18-55 years.	LPR supplementation can accentuate body-weight loss and seems to help obese women to maintain healthy body weight.	[27]
A DB, randomized, prospective study to evaluate the impact of perinatal probiotic intervention (L. rhamnosus GG - ATCC 53103) on childhood growth patterns and the development of overweight during a 10-year follow-up.	159 women before delivery and 113 children were measured at the ages of 3, 6, 12 and 24 months and 4, 7 and 10 years.	Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life.	[29]
A multicenter, DB, RPCT to evaluate the effects of the probiotic L. gasseri SBT2055 (LG2055) - originated from the human gut - on abdominal adiposity, body weight and other body measures.	87 healthy adults (59 men/ 28 women) with BMI of 24.2-30.7?kg/m² and abdominal visceral fat area (81.2-78.5?cm²).	LG2055 consumption promoted a significant reduction in abdominal adiposity, BMI, waist and hip circumference.	[33]
A DB, RPCT parallel pilot study to evaluate the effects of a hypocaloric diet supplemented with a probiotic cheese containing L. plantarum strain TENSIA on obese hypertensive patients.	25 obese hypertensive patients.	The hypocaloric diet supplemented with a probiotic cheese helped to reduce BMI.	[45]
A DB, RPCT to assess the beneficial effects on MetS of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with Streptococcus thermophilus,� L. acidophilus, B. infantis.	101 healthy adults� (70 women and 31 men), 20-65 years.	The functional yogurt NY-YP901 with probiotics reduced body weight and BMI.	[50]

Study	Population	Conclusion	Reference��
A DB, RPCT to investigate the effect of L. salivarius Ls-33 on a series of biomarkers related to inflammation and the MetS.	50 obese adolescents (28 female and 22 male), 12-15 years.	No evidence of any beneficial effect on lipid profile.	[13]
A DB, RPCT to assess the cholesterol-lowering clinical efficacy and safety of microencapsulated L. reuteri NCIMB 30242 supplemented in a yogurt formulation.	114 healthy hypercholesterolaemic adult men and women, 18-74 years.	Microencapsulate L. reuteri yoghurt consumption decreased LDL-C, TC and non-HDL-C.	[28]
A DB, RCT to investigate the effects of probiotic (L. acidophilus La5 and B. lactis Bb12) and conventional yogurt on the lipid profile.	60 adults (23 men and 37 women) with T2D and LDL-C > 2.6 mmol/L, 30-60 years.	Probiotic yogurt improved TC and LDL-cholesterol.	[35]
A RPCT to verify and compare the effects of probiotic (L. casei subsp. casei) and conventional yoghurt on the plasma lipid profile.	33 healthy, non-smoking, normocholesterolemic women, 22-29 years.	The total/HDL and LDL/HDL-C ratios improved in both probiotic and conventional yogurt intake.	[36]
A DB, RPCT to assess the beneficial effects on MetS of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with Streptococcus thermophilus,� L. acidophilus, B. infantis.	101 healthy adults� (70 women and 31 men), 20-65 years.	The functional yogurt NY-YP901 with probiotics reduced LDL-C.	[50]
A triple blind, randomized study to test the effect of probiotic (L. acidophilus La5 and B. lactis Bb12) and conventional yogurt on the lipid profile.	90 women, 19-49 years.	Decrease in cholesterol, increase in HDL-C, decrease in total:HDL-C ratio) were observed in both yogurt groups.	[51]
A single-blind, RCOT to compare the effect of consuming probiotic yogurt (L. acidophilus and B. lactis) with that of ordinary yogurt on serum cholesterol level.	14 adults (10 men and 4 women) 40-64 years with mild to moderate hypercholesterolemia.	Cholesterol-lowering effect.	[52]
A single-blind, RPCT to investigate the effect of probiotic capsules (L. acidophilus DDS-1 and B. longum UABL-14) on plasma lipid concentrations.	55 normocholesterolemic adults (33 premenopausal women and 22 men), 18-36 years.	No evidence of any beneficial effect on plasma lipids.	[53]
A single-center, DB, placebo-controlled study to assess the effects of PCC� L. fermentum on LDL cholesterol and other lipid fractions.	44 adults (16 men and 28 women) 30-75 years.	No major effect of Lactobacillus fermentum on serum lipids.	[54]
A single-blind, parallel group study to demonstrate the effect of milk fermented by B. longum strain BL1 on blood lipids.	32 healthy males with serum TC levels within the range of 220 to 280 mg/dl. 35-52 years.	B. longum yogurt lowered serum TC, especially in subjects with moderate hypercholesterolemia.	[55]
A randomized, DB, placebo-and compliance-controlled, parallel study to investigate the effect of a probiotic milk product containing the culture CAUSIDO� and of two alternative products on risk factors for cardiovascular disease.	70 healthy, weight-stable, overweight and obese adults (20 men and 50 women) 18-55 years.	CAUSIDO� culture reduced LDL-cholesterol.	[56]

Study	Population	Conclusion	Reference��
A DB, RPCT to investigate the effect of L. salivarius Ls-33 on a series of biomarkers related to inflammation and the MetS.	50 obese adolescents (28 female and 22 male), 12-15 years.	No evidence of any beneficial effect on, glucose homeostasis.	[13]
A RPCT to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS and other parameters related to cardiovascular risk.	24 postmenopausal women with MetS, 60-75 years.	L. plantarum consumption decreased glucose levels.	[15]
A DB, RPCT to investigate the effects of the widely applied probiotic strain L. acidophilus NCFM on insulin sensitivity and the systemic inflammatory response.	45 men with T2D, impaired or normal glucose tolerance.	L. acidophilus NCFM intake preserved insulin sensitivity compared with placebo.	[32]
A randomized, prospective, parallel-group intervention study to investigate whether supplementation of probiotics (L. rhamnosus GG, ATCC 53 103 and B. lactis Bb12) with dietary counselling affects glucose metabolism.	256 pregnant women (mean age of 30 years).	Combined dietary counselling and probiotics intervention yielded improved glucose metabolism and insulin sensitivity.	[57]
A DB, RPCT to investigate the effect of a probiotic capsule (L. salivarius UCC118) on maternal fasting glucose.	175 pregnant women with BMI from 30.0 - 39.9 kg/m2. Age > 18 years.	No influence on maternal fasting glucose, metabolic profile or pregnancy outcomes.	[62]

Study	Population	Conclusion	Reference��
A DB, RPCT to investigate the effect of L. salivarius Ls-33 on a series of biomarkers related to inflammation and the MetS.	50 obese adolescents (28 female and 22 male), 12-15 years.	No evidence of any beneficial effect on inflammatory markers.	[13]
A RPCT to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS and other parameters related to cardiovascular risk.	24 postmenopausal women with MetS, 60-75 years.	L. plantarum consumption decreased homocysteine levels.	[15]
A DB, RPCT to investigate the effects of the widely applied probiotic strain L. acidophilus NCFM on insulin sensitivity and the systemic inflammatory response.	45 men with T2D, impaired or normal glucose tolerance.	L. acidophilus NCFM intake did not affect the systemic inflammatory response.	[32]

Study	Population	Conclusion	Reference��
A DB, RPCT parallel pilot study to evaluate the effects of a hypocaloric diet supplemented with a probiotic cheese on obese hypertensive patients.	25 obese hypertensive patients.	The hypocaloric diet supplemented with a probiotic cheese helped to reduce arterial BP.	[45]
A DB, RPCT parallel group study to evaluate the effects of two doses of lactotripeptides (from Lactobacillus helveticus LBK-16H-fermented milk products) on 24-h ambulatory blood pressure and lipidomics profiles in mildly hypertensive subjects.	89 mildly hypertensive subjects.	Mild, but not significant decrease of blood pressure.	[70]
A DB, RPCT to study the antihypertensive effect of Lactobacillus helveticus FM in prehypertensive and borderline hypertensive subjects.	94 prehypertensive and borderline hypertensive subjects.	No significant antihypertensive effect.	[71]
A DB, RPCT to evaluate the effect and safety of powdered fermented milk with Lactobacillus helveticus CM4 on subjects with high-normal blood pressure or mild hypertension.	40 subjects with high-normal blood pressure and 40 subjects with mild hypertension	Decrease in blood pressure.	[72]
A RCOT to evaluate the effect on BP in subjects with mild hypertension of a new sour milk containing tripeptides (from Lactobacillus helveticus).	60 subjects with mild hypertension (36 men, 24 women).	Modest decrease in blood pressure.	[73]
A DB, RPCT to assess the effect of sour milk, containing two tripeptides (valine-proline-proline and isoleucine-proline-proline), on blood pressure (BP)	6 borderline hypertensive men, 23-59 years.	Decrease in blood pressure.	[74]
A DB, RPCT to evaluate the long-term blood pressure-lowering effect of milk fermented by Lactobacillus helveticus LBK-16H in hypertensive subjects.	39 hypertensive patients.	Decrease in blood pressure.	[75]

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

Abstract

Abbreviations

Introduction

Probiotics

Probiotics and body weight

Probiotics and blood lipids

Probiotics and glucose homeostasis

Probiotics and inflammatory markers

Probiotics and blood pressure

Safety considerations

Prebiotics

Synbiotics

Conclusion

References