Therapeutic and Nutritional Effects of Synbiotic Yogurts in Children and Adults

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Therapeutic and Nutritional Effects of Synbiotic Yogurts in Children and Adults: a Clinical Review

Vahid Mofid¹&Anahita Izadi²&Sayed Yousef Mojtahedi³&Leila Khedmat⁴

#Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract

Synbiotic yogurts (SYs) are potential natural cures with improved health outcomes and prevention and control of chronic diseases through the synergistic action of probiotic bacteria and prebiotic compounds. Recent clinical achievements in consuming SYs in healthy and patient pediatric and adult populations were critically reviewed. Some forthcoming challenges and interesting solutions to increase healthy nutritional effects of these dairy products have also been addressed. The use of SY-based nutrition pattern in children can considerably increase their body’s immunity with an improvement in social and school functioning. SY consumption not only reduces childhood digestive problems but also remarkably decreases the illness duration and symptoms’

severity. Increasing the number of bifidobacteria and lactobacilli in gastrointestinal (GI) tract of healthy adults consuming SYs can significantly reduce the pathogenic bacteria in feces. The regular intake of SYs with enhanced bioavailability of bioactive compounds in a short intestinal transit time reduces the risk of cardiovascular disease among hypercholesterolemic adults. Also, a meaningful improvement in the health status of adult patients with irritable bowel syndrome and nonalcoholic fatty liver disease has been assessed after eating this bio-functional supplement product. Administration of a healthy SY-based diet purposefully alters microbiota composition, provides a microbial balance in the gut, and promotes GI functions in pediatric and geriatric age groups. Full recovery without any further complications during the follow-up period in elderly patients can also be obtained by implementing the SY-based dietary guideline.

Keywords Synbiotic yogurt . Probiotic . Prebiotic . Nutrition . Health . Functionality

Abbreviations

SY Synbiotic yogurt

sIgA Secretory immunoglobulin A SCFAs Short-chain fatty acids FOS Fructooligosaccharide XOS Xylooligosaccharide

HDL-C High-density lipoprotein cholesterol

LDL-C Low-density lipoprotein cholesterol CVDs Cardiovascular diseases

T2DM Type 2 diabetes mellitus FC Functional constipation ITT Intestinal transit time GI Gastrointestinal

GALT Gut-associated lymphoid tissue IBS Irritable bowel syndrome IBD Inflammatory bowel disease MS Metabolic syndrome

MHC Moderately hypercholesterolemic NAFLD Nonalcoholic fatty liver disease

Introduction

There is a tremendous interest in developing functional foods aiming to improve the health and well-being state, along with a significant reduction in disease progression and prevention.

The consumption of functional foods due to the high content of nutraceuticals and health-related compounds is considered as an active policy in alleviating medical costs, risk factors,

* Leila Khedmat

[email protected]

1 Department of Food Science and Technology, Faculty of Nutrition Science & Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 De

partment of Pediatric Infection Disease, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pediatric Nephrology, Bahrami Children Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Health Management Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

https://doi.org/10.1007/s12602-019-09594-x

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and adverse outcomes of patients [1–4]. Today, synbiotic dairy products are one of the best nutrafoods in the world because of the health-beneficial effects of probiotic bacteria (BifidobacteriumandLactobacillusspecies) and prebiotics [5, 6]. A food product containing adequate doses of live probiotic microorganisms changes intestinal microflora and plays essential antioxidant functions in maintaining the brain and nerve systems [6–8]. These bacteria treat the gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), diabetes, and (non)-bacterial diarrhea through the competition with pathogens to attach to the intestinal mucosa and the production enhancement of bacteri- ocin and organic acids to reduce luminal pH [9–14].

Furthermore, the presence of prebiotic dietary fibers not only stimulates the growth and activity of probiotics but also pre- sents a high number of bio-functionalities on the host such as improving the immune system and gut health, and lowering the blood pressure, cholesterol, inflammation, and allergy [15, 16]. An integration of synergistically acting probiotics and prebiotics thus is defined the term of“synbiotic.”

Yogurt is the most popular milk-based product available worldwide. It has numerous health effects owing to the presence of milk nutrients, metabolites derived during lactic fermentation, and abundant accumulated biomass of Streptococcus thermophilus and Lactobacillus bulgaricus [17,18]. Noticeable attention has been recently paid to the development of novel synbiotic yogurts as attractive delivery vehicles. In clinical practice, the safe interventions according to the administration of synbiotic yogurt (SY) showed that the intake of this functional food as a biologic therapy significantly results in the improved immune health and the reduced infection risk in healthy and patient subjects. However, there is no review article on clinical results and direct healthcare effects of the intake of SYs. Therefore, the current overview highlights the recent clinical studies on the efficacy of SY supplements in maintaining/improving the health status of healthy and patient populations in different age groups.

Search Strategy

Six electronic databases were comprehensively searched to find articles in the English language (at the least with English abstract) relevant to human studies between January 2000 and August 2019. The database search engines included Scopus (Elsevier), Google Scholar, MedLine/PubMed (NLM), Nutrition & Food Sciences Database (CABI), EBSCO, and Cinahl. The principles of our search strategy were according to the combination of the following terms (A–D): A, synbiotic yogurt OR synbiotic yoghurt OR sinbiotik yogurt OR sinbiotik yoghurt OR symbiotic yogurt OR symbiotic yoghurt OR synbiotic soy yogurt OR synbiotic fermented milk OR synbiotic yogurt beverage OR synbiotic

yogurt drink OR fortified probiotic yogurt AND; B, nutrition OR nutritional OR food habit OR diet OR dietary OR consumption OR ingestion OR intake AND; C, health OR healthy OR disease OR disorder OR infection OR gastrointestinal OR therapy OR treatment AND; D, human OR patient OR children OR young OR elderly OR child OR pediatric OR adult OR women OR male. Two authors (VM and LK) of the man- uscript assigned their time to screen the title, abstract, and keywords of all recognized clinical-based studies. If a clinical investigation met the subsequent criteria, it would include in this review evaluation: (I) a randomized trial design; (II) consumption of SYs as the exposure of interest; (III) evaluation of GI disorders, school functioning, and aging-related diseases;

and (IV) relative risk or health improvement with a 95% con- fidence interval between the intervention and control groups.

Four studies were only excluded because of their interventions, not meeting the inclusion criteria itemized for the review. It is worth recalling that all references cited in articles found in scientific databases were assessed to make the most of the number of relevant investigations.

Formulation Development of Synbiotic Yogurts

Tables 1,2, and 3 exhibit probiotic bacteria and prebiotic ingredients used to develop and administrate SYs to children and adults. In these clinical trials, a high number of bifidobacteria (e.g., B. animalis subsp. lactis Bb-12 and B. lactis B94) and lactobacilli (e.g., L. acidophilus La5, L . p l a n t a r u m M u t 7 , L . p l a n t a r u m ATC C 1 4 9 1 7 , L . f e r m e n t u m AT C C 1 4 9 3 1 , L . r h a m n o s u s G G , L. rhamnosusHN001,L. casei CRL 431, andL. paracasei) were selected to produce SYs. Although the most common prebiotic to design different SY formulations was inulin; other fiber ingredients such as sweet potato fiber, oligofructose, fructooligosaccharide (FOS); and xylooligosaccharide (XOS) were used (Tables1 and2). It has been emphasized that the count of viable probiotic cells at the consumption time should be at least 10⁶–10⁷CFU/mL or g because a number of them may inactive under the harsh GI conditions in the presence of stomach acids, bile salts, and enzymes [6]. Hence, a minimal inoculation level of 10⁷CFU/mL or g for all the used probiotics due to their susceptibility was considered. The starter and probiotic bacteria were simultaneously added to UHT [16] and pasteurized (at 80–85 °C for 30 min or 90 °C for 5 min), and homogenized (2000–2500 psi) [19] milks enriched with the prebiotic before the subsequent incubation and cooling steps [11,20,21]. Most SYs in conducted clinical trials were flavored (e.g., vanilla) before the packaging to increase the consumer preference. Miremadi et al. [22] also developed colored SYs with 20% pomegranate juice as a source rich of antioxidants, phenolics, and anthocyanins.

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Healthy-Functional Effects of Synbiotic Yogurts

Children Populations

Overall, there is a lower number of clinical investigations related to nutrition and health effects of SYs consumption in children compared with adults. Lestari et al. [19] divided 20 Indonesian children aged 8–12 years into two groups of control and intervention (receiving 50 g/day SYs for 2 weeks).

They found that the level of secretory immunoglobulin (sIgA) in saliva and feces of the intervention group is significantly increased by consuming SYs. It was assumed that the probiotic cells ofL. plantarumMut7 and some of their essential components (e.g., peptidoglycan) potentiate immune cells involved in the gut-associated lymphoid tissue (GALT) [19]. In addition, the prebiotic fiber of sweet potato in developed SYs was also able to modulate the immune defensive functions through the release of short-chain fatty acids (SCFAs, e.g., acetic, propionic, and butyric acids) during its fermentation process in the intestine [23]. Hussein et al. [24] evaluated the intake effect of SYs on the health status of 28 Egyptian boys aged ~ 14 years. The urinary anti-oxidative activities and final fecal counts of bifidobacteria and lactobacilli were significantly increased. Nonetheless, a remarkable reduction in pathogenic Enterobacteriaceae (e.g.,Escherichia coli) counts was found. The higher lactobacilli number ensures the enhanced stabilization of the intestinal barrier function by inhibiting the rise of paracellular permeability across epithelial and endothelial cells. Under this condition, the protective mechanism of probiotics is the combination of lowering intestinal pH and increasing sIgA level. Moreover, the presence of undigestible FOS could improve the immune system with an increase in the fecal bifidobacteria count and SCFAs [23,24].

Even though Falke [16] studied the effect of SY drinks on healthy school-aged American children, it was anticipated that the regular consumption of this dietary supplement could reduce sick days with a better immunity function. Also, an interesting study showed that the once-daily use of SY drinks by American children aged 1–4 years daily for 16 weeks could considerably promote their school and social functioning.

Besides, the lower fever accompanied by loose/watery stools in children group receiving SY drinks were reported [25,26].

Ringel-Kulka et al. [27] explained that the speeding-up effect of the used probiotic (B. animalis subsp.lactis Bb-12) and prebiotic (inulin) on intestinal transit has a key role in increasing frequency of bowel movements. Baştürk et al. [10] scru- tinized the clinical efficiency of synbiotic (B. lactisB94 with inulin) on Turkish children with IBS. They found that the use of food products containing probiotics and synbiotics compared with formulations enrich with prebiotics has more ad- vantages in improving many IBS complaints, including belching-abdominal fullness, bloating, constipation, and fecal Table1AsummaryoftherapeuticeffectsofdietaryinterventionswithSYinchildren Clinical trial type1

Casechildren(number, age(year),nationality)Synbioticyogurt(drink)formulationAdministrationpattern (dose,duration)Maintherapeuticandhealthfinding(s)Reference ProbioticbacteriatypePrebiotictype RDBC12,8–12year, IndonesianL.plantarumMut7 (108CFU/g)Sweetpotatofiber(2.0%)50g/dayfor2weeksMorelevelsofsecretoryimmunoglobulinA(sIgA) concentrationinsalivaandfecesthanthecontrolyogurt[19] RCT28,13.9year,EgyptianB.animalis(108 CFU/g)Inulin(2.0%)190g/dayfor3weeksReducingthepathogenicbacteriawithanimprovementin intestinalbarrierfunction[24] RBD–,13–14year,AmericanL.rhamnosusHN001 (0.003%,108 CFU/g)Inulin(3.0%)200mL/day,≤1for 1–2week(s),1month, ≥3for1month Thedesiredeffectofimprovingimmunityandreducingsick daysinchildrenconsumingsynbioticyogurtdrinks[16] RDBPC76,1–4year,AmericanB.animalissubsp.lactis Bb-12 (5×109CFU/100mL)

Inulin(1.0g)91mLor97g/dayfor 16daysMeaningfullyfewerdaysofreportedfever,improvedsocial andschoolfunctioning,andmoredayswithloose/watery stoolsinchildrenreceivingsynbioticyogurts [25,26] PRDBC248,1–3year, AustralianB.lactisCNCMI-3446 (2×109/100g)Raftilose®P95 (1.4g/100g)+acaciagum (1.4g/100g)inaratioof1:1

Twomilkdrinks/day(each 300mL),for5monthsAremarkablereductionindiarrheaillnessamongchildren attendingchildcarecenters[28] PRDBC23,4–16year,TurkishB.lactisB94 (5×109 CFU/100mL)Inulin(900mg)Twicedailyfor4weeksImprovingthebelching-abdominalfullness,bloatingafter meals,constipation,andmucusinthefeceswitha significantlyhigherfullrecoveryinpatientsconsuming synbioticyogurts [10] 1RDBC,randomizeddouble-blindedcontrolled;RBD,randomizedblockdesign;RDBPC,randomized,double-blindplacebo-controlled;PRDBC,prospectiverandomized,double-blind,controlled;RCT, randomizedcontrolled(trial)

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Table2Clinicalstudiesonhealthy-functionaleffectsinhealthyadultpopulationsreceivingSYformulations Clinical trialtype1Caseadults(number,age(year), nationality)Synbioticyogurt(drink)formulationAdministration pattern(dose, duration)

MainremarksReference ProbioticbacteriatypePrebiotictype RDBPCHealthywomen(n=83), 20–60year,ArgentinianB.lactisBb12(109 –1010 CFU/g), L.caseiCRL431 (1×109 –6×1010 CFU/g)

Inulin,oligofructose (0.625g)2yogurts(125g), daily,for 2weeks Asignificantreductionintheintestinaltransittime[29] RDBCPCHealthy(n=46),31year, AmericanB.animalissubsp.lactisBb-12 (109 –1010 CFU/100-gserving)Inulin(1.0g/100-gserving)94g,daily,for 1–4week(s)Asignificantincreaseintotalbifidobacteriaalong withanotablereductioninclostridiacounts withoutanychangeinenterobacterianumber

[33] RDBPCHealthyelderlywithconstipation problems(n=12,76–90year),and adults(n=38,35–60year),Italian

L.rhamnosusGG(LGG, ~107 CFU/g)Actilight®2 (2.4%w/w)250g,daily,for 4weeksAnincreasedevacuationnumberintheelderly womenwithasignificantdetectionofLGG intheirfeces [35] RDBCHealthy(n=65),18–65year,CanadianB.lactisBb12,L.acidophilusLa5, L.caseiCRL431 (≥109 CFU/100-gserving)

Inulin(2.0g/100-gserving)200g,daily,for two15-day periods Althoughthegastrointestinaltransittimewith consumingSYwasnotchangedsignificantly, SYwithagoodtolerabilitycoulddecrease theoverallenergyintake [30] RCOHealthy(n=18),19–56year,GermanL.acidophilus145 (106–108CFU/g),B.longum 913(atleast105CFU/g)

Oligofructose(1%)300g,daily,for three7-week periods

AsignificantincreaseinHDL-CandHDL-C/LDL-C withthelong-termconsumptionofSYs[38] RPCOHealthy(n=66),22year,CzechsB.animalissubsp.lactisBb-12 (7.1×109 CFU/g), L.acidophilusLa5 (3.6×108 CFU/g)

Chicoryinulin(90%inulin +10%oligosaccharides, 2.1g/100gofSY) 200g,dailyintwo 100gportions for3week(s) Anincreaseinnumberofbifidobacteriaand L.acidophilussignificantlydecreasedcountsof clostridia,enterococci,andE.coliinfeces

[34] SGPPHealthypostmenopausalwomen (n=66),>45year,ThaisL.paracasei (4.32×1010 CFU/serving)Inulin(2.52-g/serving)180mL,twiceper day,for2weeksSignificantlyincreasedoralbioavailabilityof bioactiveisoflavones(soymilk-baseddrink)[36] 1 RDBPC,randomized,double-blindplacebo-controlled;RDBCPC,randomized,double-blind,crossover,placebo-controlled;RDBC,randomizeddouble-blindcrossover;RCO,randomizedcrossover; RPCO,randomizedparallelgroup,crossover,open-label;SGPP,single-grouppre-post(treatment) 2 Actilight®:asolubledietaryfibre-containingshort-chainfructooligosaccharide(FOS)

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Table3Clinicalstudiesonhealthy-functionaleffectsinpatientadultpopulationsreceivingSYformulations Clinical trial type1

Caseadults(number,age(year), nationality)Synbioticyogurt(drink)formulationAdministrationpattern(dose, duration)Maintherapeuticandhealthfinding(s)Reference ProbioticbacteriatypePrebiotictype RDBPPatientwithMHC2 (n=48), 30–65year,AustralianL.rhamnosus,L.acidophilus (atleast107 CFU/g)Fructooligosaccharide andinulin(FOS, 2%w/v) 200-gSYenrichedwith pomegranatejuice(20%),daily, for4and8weeks ModulatingthetotalcholesterolandLDL levelsinmildlytoMHC2 population:a positiveeffectonthereduction ofriskfactorscardiovasculardiseases [22] RDBPCPatientwithIBS2 for>6 months(n=11,18–65year), Slovenian

B.animalissubsp.lactis Bb-12(72.5×107 CFU/g), L.acidophilusLa5 (1.8×107 CFU/g) Inulin(90%), oligofructose(10%)180g,twiceperday,for 2weeksNosignificanteffectonthenumberof Enterobacteriaceae,Lactobacillus, Bifidobacterium,and/orallbacteria. Atransientlyincreaseinthepercentageof sequencesassignedtoS.thermophilus

[20] RDBPCPatientwithT2DM2 (n=10), 50–60year,BrazilianL.acidophilus(108 CFU/mL), B.bifidum(108 CFU/mL)Oligofructose(2.0g)200mL,daily,for30daysAsignificantreductioninlevelsoftotalcholesterol, totaltriglycerides,andfastingglycemiawiththeSY consumption ThesignificantincreaseinHDL-Cwith thedailyintakeofSY

[46] RCTPatientwithNAFLD2 (n=102, 40year),IranianB.animalissubsp.lactisBb-12 (108 CFU/mL)Inulin(1.5g)300g,daily,for24weeksSignificantlyimprovedhepaticsteatosisand liverenzymelevelsinpatientswithNAFLD[1] RCTWomenwithFC2(n=266, ~35year),ArgentineanB.animalisDN173010 (108CFU/g)FOS(0.5%w/v)125g,twiceperday,for 14daysAsubstantialupgradingintheparameters relatedtobowelevacuationwith theSYintake SY:abeneficialandsafefoodtomanageconstipation[47] RDBCPatientwithMS2 (n=44), 20–65year,IranianB.lactisBb-12(atleast 107 CFU/g)Inulin(6.0g/day)250g,twoservingsper day,for10weeksSubstantiallyimprovedbodycomposition andmetabolicparametersbasedon acalorie-restricteddietwithSY [21] RCTHealthy(n=16,~35.5year), patientwithIBS2 (n=8, ~39year),Iranian

L.plantarumATCC14917, L.fermentumATCC14931 (atleast107 CFU/g) Xylooligosaccharide (XOS,3%w/v)100g,daily,for4weeksIncreasingthefecallactobacillicount andimprovingthehealthstatusof IBSpatients

[11] 1 RDBP,randomized,double-blind,parallel-group;RDBPC,randomized,double-blindplacebo-controlled;RCT,randomizedcontrolled(trial);RDBC,randomizeddouble-blindedcontrolled 2 IBS,irritablebowelsyndrome;MHC,moderatelyhypercholesterolemic;NAFLD,nonalcoholicfattyliverdisease;T2DM,type2diabetesmellitus;FC,functionalconstipation;MS,metabolicsyndrome

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mucus. Binns et al. [28] evaluated the effectiveness of a synbiotic milk formula“CUPDAY”containing the probiotic B. lactis CNCM I-3446 and the prebiotic mixture (50%

Raftilose®P95 (rich in mono-disaccharides) + 50% acacia gum) on the diarrhea occurrence in Australian children aged 12–36 months. A significant 20% decrease in the number of absence days of children attending childcare centers was reported with the consumption of CUPDAY (Table1).

Healthy Adult Populations

Table2summarizes health-beneficial effects of SYs consumption on healthy adult subjects (20–60 years) in clinical evaluations. Malpeli al. [29] reported that the daily intake of 250 g SY for 14 days meaningfully reduced the intestinal transit time (ITT) of adult women, mainly in women with initial ITT > 48 h. It seems that the presence of prebiotics (e.g., inulin and oligofructose) not only stimulates the cell growth of B. lactisBb12,L. acidophilusLa5, andL. caseiCRL431 but also provides a robust osmotic effect to increase the intestinal peristalsis motility [30]. However, Tulk et al. [31] realized that the consumption of 200 g/day SY by healthy Canadian adults (18–65 years) for two 15-day periods substantially did not alter the ITT. This discrepancy may be attributed to the difference in prebiotic type and concentration, probiotic species and strains, inoculation level of probiotics, dairy matrix with var- iable content of milk components (e.g., protein, fat, and lac- tose), and even techniques measuring the GI transit [31,32].

Palaia et al. [33] mentioned that the daily consumption of SY formulated with inulin andB. animalissubsp.lactisBb-12 in healthy, young subjects (31 years) led to a significant decrease and increase in the total number of probiotic (bifidobacteria) cells and clostridia, respectively. A similar result was also reported by Komprda et al. [34] for healthy, young populations (22 years) consuming SYs containing chic- ory inulin and probiotics ofL. acidophilusLa5. Granata et al.

[35] also observed a remarkable increase in the fecal count of L. rhamnosusGG in elderly Italian women who were daily fed with 250-g short-chain FOS-based SY for 28 days. Although Palaia et al. [33] pointed out that the enterobacteria count did not change after eating SY, a significant decrease in the fecal number of enterococci andE. coliwas assessed by Komprda et al. [34]. No change in enterobacteria number after consuming SYs in the study of Palaia et al. [33] may be due to the presence of microbial strains producing biogenic amine of tyramine in the gut facilitating adhesion of this pathogenic family of bacteria to the intestinal mucosa [36]. This difference also can be owing to the consumption amount of SYs in two clinical trials so that youth groups in the literature [33]

daily consumed 94-g SY compared with 250-g SY in the study of Komprda et al. [34]. Timan et al. [37] also confirmed that the more consumption of synbiotic dairy products like synbiotic soymilk beverages could much provide increased

the bioavailability and bioaccessibility of bioactive compounds (e.g., isoflavones) in the gut, reducing the potentially harmful bacteria (clostridia, enterococci, and E. coli).

Moreover, Kießling et al. [38] earlier reported the hypocholesterolemic effect of 1% oligofructose-based SYs supplemented withL. acidophilus145 andB. longum913 in healthy women aged 19–56 years. They found that the consumption of these SY formulations for 21 weeks could reduce the ratio of low-density lipoprotein-cholesterol (LDL-C) to high-density lipoprotein-cholesterol (HDL-C) from 3.24 to 2.48. Gmeiner et al. [39] realized that the intake of a synbiotic supplement containingL. acidophilus74–2 and oligofructose under in vitro conditions could significantly decrease the activity of β-glucuronidase. Accordingly, Kießling et al. [38]

concluded that the presence of oligofructose in developed SYs could also prevent the conversion of procarcinogens into carcinogens in the intervened women through reducing the activity of enzymes (e.g.,β-glucuronidase and nitroreductase) induced by the probiotic bacterium.

Patient Adult Populations

Clinical studies related to the effective role of SYs consumption in improving the health of adult patients are given in Table 3. The long-term use (10 weeks) of calorie-restricted diets with fortified SYs containingB. lactisBb-12 could significantly improve the body composition (e.g., fat mass and fat-free mass) and metabolic parameters in Iranian patients with metabolic syndrome (MS) aged 20–65 years [21].

Reducing the fat mass and preserving the fat-free mass were ascribed to the improved sensitivity of insulin enzyme in the presence of inulin, the utilized probiotic bacterium, and micronutrients (e.g., vitamin D and calcium). It was earlier demonstrated that the synbiotic supplements could modify gut flora leading to higher fecal pH and lower number of by- products synthesized by Gram-negative bacteria (e.g., endo- toxins). This bio-functionality suppresses the synthesis of pro- inflammatory cytokine and reduces insulin resistance in the body [40,41]. Mohammadi-Sartang et al. [21] also realized that the consumption of these fortified SYs resulted in an improvement in triglyceride and HDL-C concentrations in overweight and obese populations. More synthesis of SCFAs in the large intestine, lower levels of endotoxin, and inhibition of visceral adipocyte enlargement is biochemical mechanisms involved in the reduction of triglyceride and HDL-C in these patient groups [42]. Also, Miremadi et al. [22] successfully showed that the integration of probiotics (L. rhamnosusand L. acidophilus), prebiotics (FOS and inulin), and polyphenols of pomegranate juice in SYs modulates the total cholesterol and LDL-C levels in patients with moderately hypercholesterolemic (MHC), resulting in a decrease in cardiovascular diseases risk. Bakhshimoghaddam et al. [1] reported the developed SYs withB. animalissubsp.lactisBb-12 and inulin were

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able to improve hepatic steatosis and liver enzyme levels in Iranian patients with nonalcoholic fatty liver disease (NAFLD). Most recently, Perumpail et al. [43] reviewed that the use of prebiotic agents (such as inulin and FOS) as non- digestible food substrates affects the host immunity through selectively stimulating the growth and activity of probiotic strains in the colon, improves liver oxidative enzymes, and reduces the rate of hepatic inflammation, steatosis, and fibro- sis. Also, Sengupta et al. [44] have proved excellent hepato- protective effects of soymilk-based SYs on mice fed with a high-cholesterol diet. Besides, a significant reduction in total triglyceride and cholesterol, and LDL-cholesterol levels along with a remarkable increase in HDL-cholesterol level was reported in male Wistar rats with MS after feeding with tanduk banana flour-based SYs for 2 weeks [45]. Moroti et al. [46]

assessed the intake effect of synbiotic FOS-based milkshake inoculated withL. acidophilusand B. bifidumon glycemia and cholesterol levels in elderly patients with type 2 diabetes mellitus (T2DM). After 1-month follow-up in a randomized clinical study, they found that the consumption of this synbiotic dairy product was able to reduce glycemia with an increased HDL-C level significantly.

Researchers have evaluated the health effects of SYs consumption (100–360 g/day) for 2–4 weeks in Slovenian and Iranian adult patients with IBS [11,20]. Although the use of SYs in Slovenian patients did not lead to a significant change in the number of fecal microbiota (e.g., probiotics and Enterobacteriaceae) [20], a substantial increase in the count of fecal lactobacilli (e.g.,L. plantarum ATCC 14917 andL. fermentumATCC 14931) was reported in Iranian patients [11]. Matijašićet al. [20] concluded that the ratio of probiotic strains was shortly affected by eating the SY, while the starter ofS. thermophilusin fecal samples showed the temporary increasing trend.

Noorbakhsh et al. [11] explained the use of SYs and a higher number of lactobacilli could efficiently attenuate the inflammation rate by reversing the IBS metabolism through increasing the serum acetone concentration and decreasing levels of choline, and some essential amino acids (e.g., phenylalanine, valine, leucine, and isoleucine).

In general, the present discrepancy may be due to the difference in applied methodologies to detect microorganisms, probiotic strains, prebiotic type (XOS, inulin, and oligofructose), and administration dose and duration of SYs (Table3). Also, the ingestion effect of an innovative SY formulation (Activia®) composed of FOS and probiotic strains ofB. animaliswas investigated on the bowel habits of Argentinean women with functional constipation (FC) for 2 weeks. Results showed the consumption of Activia® could substantially improve the parameters related with bowel evacuation, such as the increased quality of stools and the decreased perception of straining effort and pain related to defecation [47].

Conclusions and Final Remarks

The current review represented the recent clinical studies about the beneficial role of SY consumption in improving the health of children and adult populations. The simultaneous presence of prebiotics and probiotics in the yogurt matrix could synergistically enhance bio-functionalities and health- promoting effects. Implementing the dietary patterns based on SYs in different populations improved the gut microbiota, the bioavailability, and bioaccessibility of bioactive compounds, body composition, and metabolic factors. Although the effect of SY intake on the reduction of blood glucose levels in rats with MS was demonstrated [48], there is a research gap to clinically evaluate the effectiveness of SY consumption on the decrease of blood sugar in diabetic adults and children.

Reducing the chemical and biological markers for cardiovascular diseases (CVDs) and cancer using the digestion of SYs was briefly mentioned in the literature. However, no in vivo and clinical studies have investigated the reduction of prevalence rate of these modern health epidemics with the long- term consumption of SYs. Thus, there is a necessity to con- duct further investigations for determining the role of different probiotic bacteria and prebiotic agents in decreasing the risk of T2DM, CVDs, and cancer types. The relative therapeutic effects of probiotic, prebiotic, and synbiotic in reducing these incident chronic diseases should be distinctively assessed in pediatric and geriatric age groups. Besides, one of the most critical challenges in these healthy-functional products is maintaining the viability and stability of probiotic bacteria in the GIT. The development of SY-microencapsulated powders using high-efficient and edible polymeric matrices would be very beneficial to achieve this goal [49]. On the other hand, there are several strategies to increase the effectiveness of probiotics and prebiotics in SY matrices. Optimizing the inclusion levels of selected probiotic strains and prebiotic agents using the modeling and simulation approach in the in vitro and in vivo measurements can sufficiently regulate the activity and growth of viable probiotic bacteria reducing the symptoms of infective diseases. Increasing the polymerization degree of the used prebiotics in SY formulation may enhance their effectiveness in the fermentation activity and bacterial community composition [50,51]. Also, the physiological effect of the integrated and simultaneous use of short-chain and long- chain prebiotics (such as fructans) would be more compared with that of each prebiotic fraction [52,53]. Recently, the use of enzymatic treatments on sources enriched with FOS could result in an increase of FOS level with the improved antioxidant and prebiotic characteristics [54]. Therefore, the selection of superior enzyme and the optimization of enzymatic conditions might be effective in promoting the prebiotic effects of available natural products to be formulated in the development of SYs. Generally speaking, the daily consumption of these functional foods can be considered as a promising remedy for

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hepatoprotection and the control of risk factors of cardiovascular diseases, diabetes, and even cancer types. However, further clinical evaluations in comparable populations (age, gen- der, health status, administration dose, and duration, etc.) are required to study dietary effects of SYs on the improvement of GI and immune systems.

Compliance with Ethical Standards

Conflict of Interest The authors declare that they have no conflict of interest.

Ethical Approval This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent Formal consent was not required considering the type of the present study.

References

1. Bakhshimoghaddam F, Shateri K, Sina M, Hashemian M, Alizadeh M (2018) Daily consumption of synbiotic yogurt decreases liver steatosis in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial. J Nutr 148(8):1276–1284

2. Sivieri K, Freire FC, Lopes NP, Shiraishi CT, Pires AC, Lima AC, Zavarizi AC, Sgarbosa L, Bianchi F (2017) Synbiotic yogurts and the elderly. In: Shah NP (ed) Yogurt in health and disease prevention. Academic Press, pp. 259-271

3. Mojtahedi SY, Izadi A, Seirafi G, Khedmat L, Tavakolizadeh R (2018) Risk factors associated with neonatal jaundice: a cross- sectional study from Iran. Open Access Maced J Med Sci 6(8):

1387–1393

4. Mojtahedi SY, Rahbarimanesh A, Khedmat L, Izadi A (2018) The prevalence of risk factors for the development of bacteraemia in children. Open access Maced J Med Sci 6(11):2023–2029 5. Fazilah NF, Ariff AB, Khayat ME, Rios-Solis L, Halim M (2018)

Influence of probiotics, prebiotics, synbiotics and bioactive phyto- chemicals on the formulation of functional yogurt. J Funct Foods 48:387–399

6. Salari M, Razavi SH, Gharibzahedi SM (2014) Characterising the synbiotic beverages based on barley and malt flours fermented by Lactobacillus delbrueckiiandparacaseistrains. Qual Assur Saf Crop Food 7(3):355–361

7. Shokoohi M, Razavi SH, Labbafi M, Vahidinia A, Gharibzahedi SMT (2014) Wheat sprout flour as an attractive substrate for the producing probiotic fermented beverages: process development and product characterisation. Qual Assur Saf Crop Food 7(4):469–475 8. Sah BN, Vasiljevic T, McKechnie S, Donkor ON (2016) Antioxidant peptides isolated from synbiotic yoghurt exhibit anti- proliferative activities against HT-29 colon cancer cells. Int Dairy J 63:99–106

9. O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K (2005)LactobacillusandBifidobacteriumin irritable bowel syndrome: symptom responses and relationship to cytokine profiles.

Gastroenterology 128:541–551

10. Baştürk A, Artan R, Yilmaz A (2016) Efficacy of synbiotic, probiotic, and prebiotic treatments for irritable bowel syndrome in children: a randomized controlled trial. Turk J Gastroenterol 27:439–

443

11. Noorbakhsh H, Yavarmanesh M, Mortazavi SA, Adibi P, Moazzami AA (2018) Metabolomics analysis revealed metabolic

changes in patients with diarrhea-predominant irritable bowel syndrome and metabolic responses to a synbiotic yogurt intervention.

Eur J Nutr 3:1–10

12. Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V (2012) Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition 28(5):539– 543

13. Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V, Akbarian-Moghari A (2011) Effect of probiotic yogurt containingLactobacillus acidophilus andBifidobacterium lactison lipid profile in individuals with type 2 diabetes mellitus. J Dairy Sci 94(7):3288–3294

14. Asemi Z, Jazayeri S, Najafi M, Samimi M, Mofid V, Shidfar F, Shakeri H, Esmaillzadeh A (2012) Effect of daily consumption of probiotic yogurt on oxidative stress in pregnant women: a randomized controlled clinical trial. Ann Nutr Metab 60(1):62–68 15. Irvine SL, Hekmat S (2011) Evaluation of sensory properties of

probiotic yogurt containing food products with prebiotic fibres in Mwanza, Tanzania. Food Nutr Sci 2(5):434–439

16. Falke S (2015) Development of a synbiotic drinkable yogurt for school-aged children. In: Doctoral dissertation, Kansas State University

17. Ladjevardi ZS, Gharibzahedi SM, Mousavi M (2015) Development of a stable low-fat yogurt gel using functionality of psyllium (Plantago ovataForsk) husk gum. Carbohydr Polym 125:272–280 18. Gharibzahedi SM, Chronakis IS (2018) Crosslinking of milk pro- teins by microbial transglutaminase: utilization in functional yogurt products. Food Chem 245:620–632

19. Lestari LA, Setyabudi FS, Julia M, dan Amalia LD (2003) Effect of synbiotic yogurt made with indigenous probioticLactobacillus plantarumMUT7 and sweet potato fiber (Ipomoea batatas) in healthy children. Int Res J Microbiol 4(3):98–102

20. MatijašićBB, Obermajer T, Lipoglavšek L, Sernel T, Locatelli I, Kos M,Šmid A, Rogelj I (2016) Effects of synbiotic fermented m i l k c o nt a i n i n g L ac t o b a c i l l u s a c i d o p hi l u s L a - 5 a n d Bifidobacterium animalisssp.lactisBB-12 on the fecal microbiota of adults with irritable bowel syndrome: a randomized double- blind, placebo-controlled trial. J Dairy Sci 99(7):5008–5021 21. Mohammadi-Sartang M, Bellissima N, de Zepetnek JT, Brett NR,

Mazloomi SM, Fararouie M, Bedeltavana A, Famouri M, Mazloom Z (2018) The effect of daily fortified yogurt consumption on weight loss in adults with metabolic syndrome: a 10-week randomized controlled trial. Nutr Metab Cardiovasc Dis 28(6):565–574 22. Miremadi F, Sherkat F, Stojanovska L (2017) Health promoting

effect of synbiotic yogurt containing pomegranate polyphenols:

scientific evidence. Maturitas 100:141

23. Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA (2016) Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol 5(4):e73

24. Hussein L, Gouda M, Fouad M, Labib E, Bassyouni R, Mohammad M (2014) Dietary intervention with yoghurt, synbiotic yogurt or traditional fermented Sobya: bio-potency among male adolescents using five bio-markers of relevance to colonic metabolic activities.

Food Nutr Sci 5(12):1131–1144

25. Ringel-Kulka T, Kotch JB, Jensen ET, Savage E, Weber DJ (2015) Randomized, double-blind, placebo-controlled study of synbiotic yogurt effect on the health of children. J Pediatr 166:1475–1481 26. Vandenplas Y (2015) Synbiotic yogurt consumption leads to statis-

tical improvements in child health that may not be clinically relevant. BMJ Evid-Based Med 20(6):207

27. Ringel-Kulka T, Palsson OS, Maier D, Ringel Y (2008) Yogurt containing the probiotic bacteriaBifidobacterium lactisBB12 and prebiotic inulin significantly improves of colonic transit time in subjects with functional bowel symptoms. Am J Gastroenterol 103:S479