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Abstract Probiotics are live bacteria which have frequently been reported to be beneficial in preventing a wide range of diseases as well as playing a major role in treating the existing ailments. Thus far, a variety of probiotic products have been developed which can be categorized into two groups: probiotic foods and supplements. Both foods and supplements have been able to confer the health benefits claimed for them. However, it is not known which one can be clinically more efficient, and to the best of our knowledge, until now no research has been conducted to investigate this issue. The present review aims to discuss this matter, based on the evidence available in the literature. To do so, articles indexed in Pubmed and ScienceDirect between 2000 and 2011 were reviewed. The articles included the clinical trials in which either foods or supplements were used to administer the probiotics to either patients suffering from different diseases or healthy subjects. Although both foods and supplements seem to have been efficient carriers for the beneficial bacteria, to generally promote public health in communities, probiotic foods appear to be preferred to probiotic supplements.
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Critical Reviews in Food Science and Nutrition
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The comparison of food and supplement as probiotic
delivery vehicles
Aziz Homayoni Rad Ph.D a , Elnaz Vaghef Mehrabany M.Sc b , Beitullah Alipoor Ph.D b & Leila
Vaghef Mehrabany M.Sc c
a Department of Food Science and Technology, Faculty of Health and Nutrition , Tabriz
University of Medical Sciences , Tabriz , Iran
b Department of Nutrition, Faculty of Health and Nutrition , Tabriz University of Medical
Sciences , Tabriz , Iran
c Department of Nutrition, Faculty of Health , Tehran University of Medical Sciences ,
Tehran , Iran
Accepted author version posted online: 13 Aug 2014.
To cite this article: Aziz Homayoni Rad Ph.D , Elnaz Vaghef Mehrabany M.Sc , Beitullah Alipoor Ph.D & Leila Vaghef Mehrabany
M.Sc (2014): The comparison of food and supplement as probiotic delivery vehicles, Critical Reviews in Food Science and
Nutrition
To link to this article: http://dx.doi.org/10.1080/10408398.2012.733894
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The comparison of food and supplement as probiotic delivery vehicles
Aziz Homayoni Rad 1, Ph.D, Elnaz Vaghef Mehrabany 2*, M.Sc, Beitullah Alipoor 2, Ph.D, Leila
Vaghef Mehrabany 3, M.Sc
1- Department of Food Science and Technology, Faculty of Health and Nutrition, Tabriz
University of Medical Sciences, Tabriz, Iran.
2- Department of Nutrition, Faculty of Health and Nutrition, Tabriz University of Medical
Sciences, Tabriz, Iran.
3- Department of Nutrition, Faculty of Health, Tehran University of Medical Sciences, Tehran,
Iran.
* corresponding author: Department of Nutrition, Faculty of Health and Nutrition, Tabriz
University of Medical Sciences, Attar Neyshabouri St., Golgasht St., Tabriz, Iran. Email:
elnaz.vaghef@gmail.com.
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Abstract
Probiotics are live bacteria which have frequently been reported to be beneficial in preventing a
wide range of diseases as well as playing a major role in treating the existing ailments. Thus far,
a variety of probiotic products have been developed which can be categorized into two groups:
probiotic foods and supplements. Both foods and supplements have been able to confer the
health benefits claimed for them. However, it is not known which one can be clinically more
efficient, and to the best of our knowledge, until now no research has been conducted to
investigate this issue. The present review aims to discuss this matter, based on the evidence
available in the literature. To do so, articles indexed in Pubmed and ScienceDirect between 2000
and 2011 were reviewed. The articles included the clinical trials in which either foods or
supplements were used to administer the probiotics to either patients suffering from different
diseases or healthy subjects. Although both foods and supplements seem to have been efficient
carriers for the beneficial bacteria, to generally promote public health in communities, probiotic
foods appear to be preferred to probiotic supplements.
Key words
Probiotic products, health benefits, efficacy
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Introduction
The history recording beneficial properties of fermented products dates back many centuries.
Hippocrates prescribed yogurt to his patients to cure diarrhea and other intestinal disorders
(Lourens-Hattingh & Viljoen, 2001). It was early 20th century when Metchnicoff extolled the
virtues of consuming fermented dairy products and postulated his "Longevity without aging"
theory, in which he claimed that replacing the harmful bacteria indigenous to the intestines by
lactic acid producing bacteria can prolong life (Hughes & Hoover, 1995). Tissier was another
scientist who, almost at the same time, suggested that bifidobacteria which are the predominant
component of breast fed infants' gut microbiota, can relieve diarrhea in non-breast fed children
by replacing the putrefactive bacteria (Ishibashi & Shimamura, 1993).
Probiotics are defined as “live microorganisms which, when administered in adequate amounts,
confer a health benefit on the host” by the FAO/WHO (Anonymous (WHO/FAO), 2002). In
Japan a product must contain a minimum of 107 colony forming unit (CFU)/gr of probiotic
bacteria to be considered a probiotic one while the USA has developed a standard which requires
at least 108 CFU/gr of the product to label it as probiotic (De Vuyst, 2000). Generally, it is
believed that a probiotic product should provide >106108 CFU/g, or >1081010 CFU/day of
viable cells to be clinically efficacious. There is no cell count level demonstrated to guarantee a
health effect though (Champagne et al., 2011). Some of the genera used in probiotic products
are: 1) Lactic acid producing bacteria (LAB): lactobacillus, bifidobacterium, streptococcus; 2)
Non-lactic acid producing bacteria: bacillus, propionibacterium; 3) Non-pathogenic yeasts:
saccharomyces; 4) Non spore forming and non flagellated rod or coccobacilli (Saraf et al.,
2010).
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A microorganism to be called probiotic must fulfill the criteria below:
1) Its culture can be produced in industrial scale; 2) It can survive during production and storage;
3) It can tolerate the gut environment of the host and 4) It exerts health effects when consumed
(Anonymous (WHO/FAO), 2002).
Clinical benefits of probiotics in foods versus supplements
Traditionally yogurt was the first food to which probiotics were added. Recently development of
novel probiotic foods has attracted a great attention and manufacturers are coming out with new
probiotic foods including ice-cream, cheese, chocolate, beverages, cereals and vegetable
products (Ranadheera et al., 2010). Different forms of probiotic supplements are also available in
the market today, including pills, capsules, tablets, caplets, gelcaps, liquids and powders (Brink
et al., 2005). To investigate the health benefits of probiotics, both foods and supplements have
been used as delivery vehicles in clinical trials; however, no studies have been performed to
compare the efficacy of the two forms of carriers regarding clinical benefits, as far as our
literature review goes.
Probiotics have been shown to be effective against a number of disorders. Three of the mostly
documented benefits of probiotics include alleviation of gastrointestinal disorders, affecting the
elements of metabolic syndrome and modulation of immune system function, which are among
the most important health issues throughout the world. Thus in this review article, it has been
concentrated on these three conditions.
Articles were searched in two databases: Pubmed and ScienceDirect. In both databases
"Probiotics" was used as the key word. In Pubmed, search was limited to the last 11 years in the
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"dates", clinical trials in the "type of article" and English in the "languages" bar. In
ScienceDirect, the key word was searched in the title, keyword or abstract and years 2000-2011
was selected in the date range. Then clinical trials were searched within the results.
Probiotics in gastrointestinal disorders
Diarrhea is a common gastrointestinal tract disorder for the prevention and treatment of which,
probiotics have been reported to be beneficial. There are different types of diarrhea regarding
their etiology. Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use.
Also hospitalized patients exposed to antibiotics may develop Clostridium difficile disease
(CDD). Diarrhea in these two conditions is attributed to disruption of intestinal microbiota by
antibiotics. Probiotics may be a suitable option for treating diarrhea in AAD and CDD by
reestablishing the disrupted intestinal microbiota, enhancing immune responses and clearing
pathogens and their toxins from the host (Mcfarland et al., 2006). However, more clinical trials
are warranted to propose the most suitable strain and dosage to most efficiently alleviate diarrhea
in these cases (Ejtahed & Homayouni, 2010). Diarrhea can also be a result of radiation therapy to
pelvic malignancy. Radiation causes changes in bacterial flora, the vascular permeability of the
mucosal cells and intestinal motility. Animal and human studies have revealed that probiotics
can reduce the incidence and severity of diarrhea during pelvic radiotherapy. There in need for
more clinical trials to draw a critical conclusion in this regard (Chitapanarux et al., 2010; Ejtahed
& Homayouni, 2010). Bacterial diarrhea is a common problem for many travelers.
Saccharomyces cerevisiae has been shown to efficiently alleviate diarrhea in travelers, but
lactobacillus GG and lactobacillus acidophilus have failed to ease the symptoms. This may
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indicate that bacterial diarrhea is affected only by saccharomyces cerevisiae, while lactobacilli
are more effective in viral diarrheas (Briand et al., 2006; Ejtahed & Homayouni, 2010).
Acute diarrhea typically affects infants and children. This type of diarrhea is associated with 20
viruses, bacteria and parasites; but worldwide, rotavirus is the most common cause of severe
diarrhea and diarrhea mortality in children (Allen et al., 2010). This review has mainly focused
on acute infectious diarrhea, since it is more prevalent and the majority of studies linking
probiotics to diarrhea have been performed in this field. In table 1, clinical trials investigating the
effects of probiotic supplementation on acute infectious diarrhea have been summarized. In these
trials, incidence, frequency and duration of diarrhea, hospital stay and fecal rotavirus excretion
have been used as indicators of the effect probiotics have left on patients. Figure1 shows the
many routes through which probiotics may be effective in reducing incidence, severity and
duration of diarrhea (Allen et al., 2010; Ejtahed & Homayouni Rad, 2010; Homayouni Rad,
2008).
Probiotics have also been tried in attempt to improve symptoms of lactose maldigestion or
intolerance. It's crucial to discriminate between these two concepts. Lactose maldigestion results
from lower than normal concentration of lactose cleaving enzyme, β-galactosidase (also called
lactase) in the brush border membrane of the mucosa of the small intestine. There are several
forms of lactose maldigestion; in primary lactose maldigestion or adult maldigestion, lactase
concentration is high at birth but decreases gradually as the age goes up and reaches a stable
level at adulthood. This type of lactose maldigestion is a physiologic situation for mammals and
humans. Secondary forms of maldigestion can result from inflammation or functional loss of the
small intestinal mucosa and by protein-energy malnutrition. Secondary lactose maldigestion is
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usually irreversible even after the recovery of the original disease. Congenital lactose
maldigestion is a rare autosomal-recessive heritable genetic defect and can be detected
immediately after birth, as the infant responds to the first milk with diarrhea. Breath hydrogen is
a reliable indicator for lactose maldigestion. Lactose maldigestion accompanied by clinical
symptoms such as bloating, flatulence, nausea, diarrhea and abdominal pain is defined as lactose
intolerance. Studies have shown that reduction in breath hydrogen is not necessarily followed by
improvement of clinical manifestations. Fermented dairy products have been shown to efficiently
reduce the symptoms of lactose intolerance in lactose maldigesters. This has been attributed to
microbial β-galactosidase content of the (fermented) milk product, delayed gastrointestinal
transit, positive effects on intestinal functions and colonic microbiota, and reduced sensitivity to
symptoms. Studies have revealed that probiotics, in order to alleviate symptoms in lactose
intolerant subjects, must be alive or at least have an intact cell wall once they reach the small
intestine. This is crucial for the protection of enzyme, β-galactosidase from the acidity of the
stomach (Mustapha et al., 1997; Rampengan et al., 2010; De Vrese et al., 2001). A systemic
review article by Levri and colleagues (2005), based on results from studies performed between
1966 and 2002, concluded that only specific strains, concentrations and preparations of
probiotics might be effective in reducing the symptoms in lactose maldigesters. Clinical trials
performed in the last 11 years on the effect of probiotics in lactose intolerant patients have been
presented in table 1.
The number of clinical trials in which foods were used as probiotic delivery vehicles, are limited.
This may be justified by the fact that it is easier to administer supplements than foods to the
infants in which acute diarrhea is most prevalent and who are the major target group when
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studying the effects of probiotics in alleviating acute diarrhea. Though not conclusive, all these
trials revealed that probiotic foods could be beneficial in children affected by acute diarrhea, in
some way (Pedone et al., 2000, Chouraqui et al., 2004, Lei et al., 2006). As far as our review
goes, no clinical trial was performed to investigate the effects of probiotic foods in lactose
maldigesters.
Supplementation with probiotics has been beneficial for the patients with acute diarrhea
(Guandalini et al., 2000, Lee et al., 2001, Rosenfeldt et al., 2002, Sarker et al., 2005, Szimanski
et al., 2006, Vivatvakin et al., 2006, Canani et al., 2007, Basu et al., 2009, Kianifar et al., 2009,
Chen et al., 2010, Ritchie et al., 2010) and lactose intolerants (He et al., 2008, Rampengan et al.,
2010) in most trials. However, some investigations have failed to exert such effects (Costa-
rebeiro et al., 2003, kowalska-Duplaga et al., 2004, Basu et al., 2007, Yesovitch et al., 2004).
Varying outcomes from different studies may result from different study settings. It is also
noteworthy that different populations may respond differently to the same intervention, for they
have different gut microbiota as a result of different styles of life and nutrition.
Probiotics in metabolic syndrome
The metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, overweight
and abdominal fat distribution, mild dyslipidemia and hypertension is such an important issue in
today's world, mostly because of its association with subsequent development of type 2 diabetes
mellitus and cardiovascular diseases (Lakka et al., 2002). It has been shown that the composition
of intestinal microbiota in obese subjects differs from that of lean ones. Human studies on fecal
microbial ecology have revealed some connection between weight loss and the abundance of
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bacteroides-related taxa. However these results are not conclusive. Unlike human studies, animal
studies have come up with less variable outcomes; results generally support patterns of greater
firmicutes/bacteroidetes ratios in obesity models. In addition, specific bacteria were related to the
obese phenotype (halomonas and sphingomonas), as were lower total bacterial counts and lower
bifidobacterial counts. The question whether changes in gut microbiota is only a result of obesity
or can play a causal role in its development, has been answered by animal studies in which gut
microbiota was manipulated by administering particular bacteria to germ-free rodents. Results
showed that animals fed obese microbiotas gained greater weight compared to the other group,
on an isocaloric diet (Ley, 2010). Not many clinical trials have used probiotics to modify the gut
microbiota in order to combat obesity. Possible mechanisms through which intestinal microbiota
can affect body weight are summarized in figure 2 (Musso et al., 2010). Three main ways
through which energy harvest is implicated by gut microbiota are: 1) obese gut microbiome is
depleted of genes involved in motility (chemotaxins, motility proteins, flagellar assembly) and
enriched in enzymes capable of breaking down otherwise indigestible alimentary components, 2)
gut microbiota on a high-fat diet may convert dietary choline into hepatotoxic methylamines,
reducing bioavailability of choline, which is necessary for the assembly and secretion of very
low density lipoproteins (VLDLs) and ultimately enhancing hepatic steatosis, insulin resistance
and lipoperoxidation, 3) microbiota may modulate host hepatic and systemic lipid metabolism
through modification of bile acid conjugative patterns, directly influencing emulsification and
absorption properties of bile acids and indirectly affecting hepatic fat storage and
lipoperoxidation through bile acid signaling properties. Gut microbiota can also affect fatty acid
metabolism; mammalian intestinal lactobacilli and bifidobacteria can synthesize bioactive
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isomers of conjugated linoleic acid from free linoleic acid. The isomers of conjugated linoleic
acid have antidiabetic, anti-atherosclerotic, immunomodulatory, and anti-obesity properties (Ley,
2010).
Bacteria residing the gut can ferment indigestible carbohydrates to short chain fatty acids
(SCFAs), mainly acetate, propionate and butyrate. SCFAs bind G-protein-coupled receptors,
Gpr41 and Gpr43. These receptors stimulate secretion of PYY, a gut secreted hormone which
inhibits gut motility and slows intestinal transit thus enhances nutrient absorption (Delzenne &
Cani, 2010; Ley, 2010). PYY decreases appetite as well. This may explain how SCFAs produced
by probiotics can play a role in combating obesity (Chaudhri et al., 2008). Gut microbiota
fermentation of prebiotics has been shown to promote L-cell differentiation in the proximal
colon. These cells secrete glucagon-like peptide (GLP) 1 and 2. GLP1 is an anorexigenic peptide
which decreases postprandial blood glucose by stimulating insulin secretion and inhibiting
glucagon release. GLP2 plays a role in modulating gut barrier integrity (Sanz et al., 2010; Ley,
2010).
Low-grade metabolic inflammation is recognized as an important element in obesity and
metabolic syndrome. Metabolic systems are incorporated functionally and molecularly with
immune responses. For example the increase in pro-inflammatory cytokines, such as tumor
necrosis factor- (TNF -), typical of obesity-related inflammation, has been shown to result in
insulin resistance. Studies have found that gut bacteria can initiate the inflammation and insulin
resistance associated with obesity. On the other hand, probiotics, through modulating the
immune system function, have performed well in reducing inflammation and the insulin
resistance following it. Activity of lipopolysaccharide (LPS), an essential component of the cell
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walls of Gram-negative bacteria such as the bacteroidetes is one main route by the means of
which, bacteria can impact inflammation and insulin resistance. LPS can trigger the
inflammatory process by binding to the CD14 toll-like receptor-4 (TLR-4) complex at the
surface of innate immune cells (Caesar et al., 2010; Duncan et al., 2003; Ley, 2010; Lye et al.,
2009; Pickup, 2004). More details on how probiotics can trigger different aspects of immune
system are presented in the upcoming section.
Hypertension may be either primary which is diagnosed with no known cause, or secondary
which may result from pregnancy, diseases such as sleep apnea, Cushing’s syndrome, kidney
malfunction, and as a side-effect of various drugs. The exact causes of primary hypertension
remain unclear; however, factors that augment the risks of primary hypertension have been
identified including obesity, hypercholesterolemia, diabetes, increased physiological production
of renin and an imbalanced sexual hormones profile. Obesity results in increased leptin
production from adipocytes. Leptin over-activates sympathetic nervous system which leads to
lipid profile alters and increased blood pressure by causing peripheral vasoconstriction and
increasing renal tubular sodium reabsorption. Insulin's vasodilatory effects are prevented and
sympathetic and the antinatriuretic tone, are upregulated as a result of insulin resistance and its
attendant hyperinsulinemia. Rennin is a proteinase which plays a key role in renin-angiotensin
system by hydrolyzing angiotensinogen to yield the inactivate angiotensin I. Angiotensin-
converting enzyme (ACE) converts angiotensin I to angiotensin II which causes vasodilation and
induces release of aldosterone and thus increases sodium concentration which in turn elevates
blood pressure. Moreover, hypertension can result from imbalances in hormones such as
estrogen, progesterone and aldosterone (Lye et al., 2009).
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There is strong evidence that probiotics can exert antihypertensive properties through modulating
the underlying causes of primary hypertension, mentioned herein. How probiotics can affect
body weight and insulin resistance, was briefly discussed above (Lye et al., 2009). Figure 3
presents the possible routes by the means of which probiotics can impact blood cholesterol level
(Lye et al., 2009; Ooi & Liong, 2010). As mentioned previously, angiotensin II, the potent
vasoconstrictor is converted from angiotensin I by ACE. ACE can contribute to elevations in
blood pressure by inactivating the vasodilator, bradykinin as well. Hence, both angiotensin II and
bradykinin levels which play the major role in regulating blood pressure are dictated by ACE.
ACE inhibitory peptides which reduce production of angiotensin II and inhibit degradation of
bradykinin are inactive within the sequence of a parent protein. Release of ACE inhibitory
peptides from the parent protein through proteolytic action explains how probiotics can exert
antihypertensive effects (Lye et al., 2009).
There is strong epidemiological evidence that hypertension is associated with hormonal
imbalances. Estrogen and progesterone serve as antihypertensive sex hormones, antagonizing the
pro-hypertensive effects of testosterone with direct effects on the vascular, renal and heart cells;
or even via indirect effects mediated by humoral factors. Hormone replacement therapy is
usually prescribed to postmenopausal women or men, to prevent hypertension. Phytoestrogens
are naturally occurring dietary compounds which can mimic the physiologic roles of estrogen.
Phytoestrogens are more efficiently absorbed when the glycoside on their phenolic ring is
hydrolyzed. Probiotics can facilitate phytoestrogen take up for they contain β-glucosidase (Lye et
al., 2009). Clinical trials investigating the effects of probiotic supplementation on different
aspects of metabolic syndrome are summarized in table 2. Only one clinical trial was performed
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in which the effect of probiotic ingestion in preventing obesity was investigated. Fermented milk
was used as the delivery vehicle in this study. The intervention could decrease abdominal,
visceral and subcutaneous fat significantly (Kadooka et al., 2010). Based on the results from
different studies performed in various disorders related to metabolic syndrome including obesity,
diabetes, hypertension and hypercholesterolemia, foods have been better carriers for probiotics
than supplements in conferring the desired benefits.
Probiotics in immune function
Our intestine is colonized by a great number of microorganisms, the composition of which is
influenced by the combination of food practices, geographical localization, various levels of
hygiene or various climates. This colonization facilitates the formation of a physical and
immunological barrier between the environment and us. The immune properties of the digestive
mucosa are provided by the gut-associated lymphoid tissue (GALT). GALT is composed of
lymphoid aggregates, including the Peyers patches (located mainly in the small intestinal distal
ileum), where stimulation of immune responses occurs, and mesenteric lymphoid nodes. In
addition, there are large amounts of immune-competent cells in the lamina propria and the
mucosal epithelium. The intestine also protects us from pathogens because its epithelium is
covered by mucus and avoids any direct contact with the microorganisms.
Many in vitro and in vivo studies have been performed to investigate the effects of probiotic
bacteria on different aspects of immune function. Results have revealed that probiotics can affect
immune function in many ways and the outcomes are strongly strain specific. It has also been
shown that probiotics, not only stimulate immune system locally, but also affect both innate and
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adaptive immune responses, systemically. It is also noteworthy that direct contact between the
probiotic bacteria and the epithelial cells has been proposed to be essential for the GALT to be
induced (Delcenserie et al., 2008). The possible mechanism through which probiotics induce
immune response is presented in figure 4. Dentritic cells (DCs) present in the lamina propria can
sample the luminal bacterial antigens through two routes, either by passing their dendrites
between intestinal epithelial cells (IECs) into the gut, or by direct interact with the bacteria that
have gained access to the dome region of the GALT which is due to the specialized cells called
microfold cells (M cells) that can transfer the bacteria intact to the lower layers. The
microorganism-associated molecular patterns (MAMPs) that are present on the surface
macromolecules of probiotic bacteria are recognized by the host pattern recognition receptors
(PRRs). PRRs which can perceive probiotic signals include Toll-like receptors (TLRs) and the C
type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN).
Important responses of DCs against probiotics include the production of cytokines, major
histocompatibility complex (MHC) molecules for antigen presentation and co-stimulatory
molecules that polarize T-cells into T helpers or regulatory T cells in the mesenteric lymph nodes
(MLNs) or subepithelial dome of the GALT (Lebeer et al., 2010). Clinical trials published in
Pubmed and ScienceDirect during the last 11 years in this regard are presented in table 3. Both
foods and supplements have widely been used as carriers to provide the subjects with probiotics
in trials investigating the effects of probiotics on immune system function. Among studies in
which food was used as probiotic delivery vehicle, some trials showed the results expected for
probiotics, while the others did not. This was the case for studies in which supplements were
used to administer probiotics as well. Since it is always emphasized that the effects of probiotics
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in different aspects of immune system function is strongly strain specific, this was predictable in
both food and supplement studies.
Comparison
Unfortunately thus far no studies have been performed to compare the efficacy of foods versus
supplements as probiotic delivery vehicles. Even regarding the results from the clinical trials
presented in the tables (1-3), it seems hard to judge whether foods or supplements have acted
more efficiently in exerting the claimed health effects; mainly because the results of different
studies is strongly dependant on the strain, dosage, period of intervention and the condition
studied.
The efficacy of probiotic bacteria is mainly based on two factors: viability (being live in food
products and supplements) and survivability (sustaining their life through harsh conditions) as
well as activity (De Vrese & Schrezenmeir, 2008). Several parameters including probiotic strain,
pH of the matrix, nutritional composition of the carrier and heat treatment can affect viability and
survivability (Bazrafshan & Homayouni Rad, 2010; Homayouni Rad et al., 2008a; Kailasapathy
& Chin, 2000; Kolida et al., 2000; Ranadheera et al., 2010; Sleator & Hill, 2008). Some
techniques have been developed for increasing bacterial viability and survivability including pre-
exposing to sublethal stresses such as salt, heat, bile and low pH, immobilized cell technology,
micro-encapsulation, genetic modification, combining different synergistic strains and
incorporation of nutrients and prebiotics to the matrix. Selection of the proper method depends
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on the type of product probiotic bacteria will be added to (Alizadeh et al., 2008; Farnworth,
2008; Homayouni Rad et al., 2008b; Homayouni Rad et al., 2008c; Sleator and Hill, 2008).
Factors affecting bacterial activity are water activity of the carrier, access to essential nutrients
for probiotic growth, pH of the matrix and growth promoters (De Vuyst, 2000).
Only one study has compared the survivability of probiotic bacteria in food vs. supplements thus
far, in which fecal bacterial count was considered the indicator of survivability. The results
showed that matrix did not influence survival of lactobacilli strains but bifidobacteria survived
better in yogurt (Saxelin et al., 2010). However, the magnitude of health effects was not
investigated and compared for different matrices in this study.
Conclusion
Returning to the hypothesis posted at the beginning of this study, it is now possible to state that
both foods and supplements have performed well as probiotic delivery vehicles. However, foods
may be preferred to supplements when public health promotion is aimed. This may be due to the
buffering properties of foods for probiotics during passage through the gut, provision of essential
nutrients for maintaining the activity and efficacy of the probiotic bacteria, synergistic effects of
food ingredients on probiotic growth and consumer attitude towards probiotic foods vs.
supplementation with tablets, capsules and other drug forms (Del Piano et al., 2011; Ranadheera
et al., 2010; De Vrese & Schrezenmier, 2008).
Acknowledgment
We sincerely thank Khosro Vaghef Mehrabany, Monireh Akhbary Mehrabany and Mina Javadi
for their very kind supports and valuable recommendations.
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References
Aihara, K., Kajimoto, O., Hirata, H., Takahashi, R., Nakamura, Y. (2005). Effect of powdered
fermented milk with lactobacillus helveticus on subjects with high-normal blood pressure or mild
hypertension. Journal of the American College of Nutrition. 24(4): 257-265.
Alizadeh, A., Homayouni Rad, A., Ehsani, M. R. (2008). Probiotic survival in yogurt made from
ultrafiltered skim milk during refrigerated storage. Research Journal of Biological Sciences.
3(10): 1163-1165.
Allen, S. J, Martinez, E. G, Gregorio, G. V, Dans, L. F. (2010). Probiotics for treating acute
infectious diarrhea. The Cochrane Library. 11: 1-124 .
Andreasen, A. S., Larsen, N., Pedersen-Skovsgaard, T., Berg, R. M., Moller, K., Svendsen, K.
D., Jakobsen, M., Pedersen, B. K. (2010). Effects of lactobacillus acidophilus NCFM on insulin
sensitivity and the systemic inflammatory response in human subjects. British Journal of
Nutrition. 104(12): 1831-1838.
Anonymous. (2002). Guidelines for the evaluation of probiotics in food, Food and Agriculture
Organization of the United Nations and World Health Organization Expert Consultation Report.
http://www.who.int/foodsafety/publications/fs_management/ probiotics2/en. 1-11.
Ataie-Jafari, A., Larijani, B., Alavi Majd, H., Tahbaz, F. (2009). Cholesterol-lowering effect of
probiotic yogurt in comparison with ordinary yogurt in mildly to moderately
hypercholesterolemic Subjects. Annals of Nutrition and Metabolism. 54: 22-27.
Bakker-Zierikzee, A. M., Tol, E. A. F., Kroes, H., Alles, M. S., Kok, F. J., Bindels, J. G. (2006).
Fecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatr Allergy Immunol.
17: 134-140.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
18
Baron, M. (2009). A patented strain of bacillus coagulans increased immune response to viral
challenge. Postgrad Med. 121(2): 114-118.
Basu, S., Chatterjee, M., Ganguly, S., Chandra, P. K. (2007). Efficacy of lactobacillus rhamnosus
GG in acute watery diarrhea of Indian children: A randomized controlled trial. Journal of
Pediatrics and child Health. 43: 837-842.
Basu, S., Paul, D. K., Ganguly, S., Chatterjee, M., Chandra, P. K. (2009). Efficacy of high dose
lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children. J Clin
Gastroenterol. 43: 208-213.
Bazrafshan, M., Homayouni Rad, A. (2010). Effect of environmental stress factors on the
survival of lactobacillus acidophilus: A review. Microbial Biotechnology Journal of Islamic
Azad University. 2(6): 47-56.
Berggren, A., Ahren, I. L., Larsson, N., Onning, G. (2011). Randomized double blind and
placebo controlled study using new probiotic lactobacilli for strengthening the body immune
defense against viral infections. Eur J Nutr. 50: 203-2010.
Briand, V., Buffet, P., Genty, S., Lacombe, K., Godineau, N., Salomon, J., Vandemelbrouck, E.,
Ralaimazava, P., Goujon, C., Matheron, S., Fontanet, A., Bouchaud, O. (2006). Absence of
efficacy of nonviable lactobacillus acidophilus for the prevention of traveler's diarrhea: a
randomized, double-blind, controlled study. Clinical Infectious Diseases. 43: 1170-1175.
Brink, M., Senekal, M., Dicks, L. M. T. (2005). Market and product assessment of
probiotic/prebiotic-containing functional foods and supplements manufactured in South Africa. J
Afr Med J. 95: 114-119.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
19
Caesar, R., Fak, F., Bached, F. (2010). Effects of gut microbiota on obesity and atherosclerosis
via modulation of inflammation and lipid metabolism. J Intern Med. 268: 320-328.
Canani, R. B., Cirillo, P., Terrin, G., Cesarano, L., Spagnuolo, M. I., De Vincenzo, A., Albano,
F., Passariello, A., De Marco, G., Manguso, F., Guarino, A. (2007). Probiotics for treatment of
acute diarrhea in children: randomized clinical trial of five different preparations. BMJ.
335(7615): 340-345.
Champagne, C. P., Ross, R. P., Saarela, M., Hansen, K. F., Charalampopoulos, D. (2011).
Recommendations for the viability assessment of probiotics as concentrated cultures and in food
matrices. International journal of food microbiology. 149: 185-193.
Chang, B. J., Park, S. U., Jang, Y. S., Ko, S. H., Joo, N. M., Kim, S. I., Kim, C. H., Chang, D. K.
(2011). Effect of functional yogurt NY-YP901 in improving the trait of metabolic syndrome.
European Journal of Clinical Nutrition. 65: 1250-1255.
Chaudhri, O. B., Wynne, K., Bloom, S. R. (2008). Can gut hormones control appetite and
prevent obesity? Diabetes Care. 31(2): S284-S289.
Chen, C. C., Kong, M. S., Lai, M. W., Chao, H. C., Chang, K. W., Chen, S. Y., Huang, Y. C.,
Chiu, C. H., Li, W. C., Lin, P. Y., Chen, C, J., Li, T. Y. (2010). Probiotics have clinical,
microbiological and immunological efficacy in acute infectious diarrhea. Pediatr Infect Dis J.
29: 135-138.
Chitapanarux, I., Chitapanarux, T., Traisathit, P., Kudumpee, S., Tharavichitkul, E., Lorvidhaya,
V. (2010). Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium
bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiation
Oncology. 5: 31-36.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
20
Christensen, H. R., Larsen, C. N., Kaestel, P., Rosholm, L. B., Sternberg, C., Michaelsen, K. F.,
Frokiaer, H. (2006). Immunomodulating potential of supplementation with probiotics: a dose
response study in healthy young adults. Immunol Med Microbiol. 47: 380-390.
Choraqui, J. P., Van Egroo, L. D., Fichot, M. C. (2004). Acidified milk formula supplemented
with bifidobacterium lactis: impact on infant diarrhea in residential care settings. J Pediatr
Gastroenterol Nutr. 38(3): 288-292.
Costa-Riberio, H., Riberio, T. C. M., Mattos, A. P., Valois, S. S., Neri, D. A., Almeida, P.,
Cerqueira, C. M., Ramos, E., Young, R. J., Vanderhoof, J. A. (2003). Limitations of probiotic
therapy in acute, severe dehydrating diarrhea. Journal of Pediatric Gastroenterology and
Nutrition. 36: 112-115.
Cukrowska, B., Lodlnova-Zadnlkova, R., Enders, C., Sonnenborn, U., Schulze, J., Tlaskalova-
Hogenova, H. (2002). Specific proliferative and antibody responses of premature infants to
intestinal colonization with nonpathogenic probiotic E. coli strain Nissle 1917. Scand. J.
Immunol. 55: 204-209.
Delcenserie, V., Martel, D., Lamoureux, M., Amiot, J., Boutin, Y, Roy, D. (2008).
Immunomodulatory effects of probiotics in the intestinal tract. Curr. Issues Mol. Biol. 10: 37-54.
Del Piano, M., Garmagnola, S., Ballare, M., Sartori, M., Orsello, M., Balzarini, M. (2011). Is
microencapsulation the future of probiotic preparations? Gut Microbes. 2(2): 120-123.
Delzenne, N. M., Cani, P. D. (2010). Nutritional modulation of gut microbiota in the context of
obesity and insulin resistance: potential interest of prebiotics. International Dairy Journal. 20:
277-280.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
21
De Vrese, M., Schrezenmeir, J. (2008). Probiotics, prebiotics and synbiotics. Adv Biochem
Engin/Biotechnol. 111: 1-66.
De Vrese, M., Stegelmann, A., Richter, B., Fenselau, S., Laue, C., Schrezenmeir, J., (2001). Am
J Clin Nutr. 73: 421S-429S.
De Vrese, M., Winkler, P., Rautenberg, P., Harder, T., Noah, C., Laue, C., Ott, S., Hampe, J.,
Schreiber, S., Heller, K., Schrezenmeir, J. (2005). Effect of lactobacillus gasseri PA 16/8,
bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind
randomized, controlled trial. Clinical Nutrition. 24: 481-491.
De Vuyst, L. (2000). Technology aspects related to the application of functional starter cultures.
Food technol. Biotechnol. 38(2): 105-112.
Duncan, B. B., Schmidt, M. I., Pankow, J. S., Ballantyne, C. M., Couper, D., Vigo, A.,
Hoogeveen, R., Folsom, A. R., Heiss, G. (2003). Low-grade systemic inflammation and the
development of type 2 diabetes. Diabetes. 52: 1799-1805.
Ejtahed, H. S., Homayouni Rad, A. (2010). Effects of probiotics on the prevention and treatment
of gastrointestinal disorders. Microbial biotechnological journal of Islamic Azad University.
2(4): 53-60 [Persian].
Ejtahed, H. S., Mohtadi-Nia, J., Homayouni-Rad, A., Niafar, M., Asghari-Jafarabadi, M., Mofid,
V. (2011a). Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition.
28(5):539-543.
Ejtahed, H. S., Mohtadi Nia, J., Homayouni Rad, A., Niafar, M., Asghari, M., Mofid, V. (2011b).
The effects of probiotic and conventional yogurt on diabetes markers and insulin resistance in
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
22
type 2 diabetes patients: A randomized controlled clinical trial. Iranian Journal of
Endocrinology and Metabolism. 13(1): 1-8.
Ejtahed, H. S., Mohtadi-Nia, J., Homayouni Rad, A., Niafar, M., Asghari-Jafarabadi, M., Mofid,
V., Akbarian-Moghari, A. (2010). Effects of probiotic yogurt containing Lactobacillus
acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes
mellitus. J Dairy Sci. 94: 3288-3294.
Farnworth, E. R. (2008). Handbook of fermented functional foods (Functional Foods and
Nutraceuticals), pp. 26-54. Taylor and Francis, New York.
Gill, H. S., Rutherfurd, K. J., Cross, M., Gopal, P. (2001). Enhancement of immunity in the
elderly by dietary supplementation with the probiotic bifidobacterium lactis HN019. Am J Clin
Nutr. 74: 833-839.
Guandalini, S., Pensabene, L., Zikri, M. A., Dias, J. A., Casali, L. G., Hoekstra, H., Kolacek, S.,
Massar, K., Micetic-Turk, D., Papadopoulou, A., de Sousa, J. S., Sandhu, B., Szajewska, H.,
Weizman, Z. (2000). Lactobacillus GG administered in oral rehydration solution to children with
acute diarrhea: A multicenter European trial. Journal of Pediatric Gastroenterology and
Nutrition. 30(1): 54-60.
Hatakka, K., Mutanen, M., Holma, R., Saxelin, M., Korpela, R. (2008). Lactobacillus rhamnosus
LC705 together with propionibacterium freudenreichii ssp shermanii JS administered in capsules
is ineffective in lowering serum lipids. Journal of the American College of Nutrition. 27(4): 441-
447.
He, T., Priebe, M. G., Zhong, Y., Huang, C., Harmsen, H. J., Raangs, G. C., Antoine, J. M.,
Welling, G. W., Vonk, R. J. (2008). Effects of yogurt and bifidobacteria supplementation on the
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
23
colonic microbiota in lactose-intolerant subjects. Journal of Applied Microbiology. 104: 595-
604.
Homayouni Rad, A. (2008). Therapeutical effects of functional probiotic, prebiotic and synbiotic
foods. Tabriz University of Medical Sciences, Tabriz [Persian].
Homayouni Rad, A., Ehsani, M. R., Azizi, A., Razavi, S. H., Yarmand, M. S. (2008a). Growth
and survival of some probiotic strains in simulated ice cream conditions. Journal of Applied
Sciences. 8(2): 379-382.
Homayouni Rad, A., Azizi, A., Ehsani, M. R., Yarmand, M. S., Razavi, S. H. (2008b). Effect of
microencapsulation and resistant starch on the probiotic survival and sensory properties of
synbiotic ice cream. Food Chem. 111: 50-55.
Homayouni Rad, A., Ehsani, M. R., Azizi, A., Razavi, S. H., Yarmand, M. S. (2008c).
Spectrophotometrically evaluation of probiotic growth in liquid media. Asian Journal of
Chemistry. 20(3): 2414-2420.
Hughes, D. B., Hoover, D. G. (1995). Viability and enzymatic activity of bifidobacteria in milk.
J Dairy Sci, 78(2): 268-276.
Ishibashi, N., Shimamura, S. (1993). Bifidobacteria: Research and development in Japan. Food
Technology, 47(6): 126, 129-134.
Jahreis, G., Vogelsang, H., Kiessling, G., Schubert, R., Bunte, C., Hammes, W. P. (2002).
Influence of probiotic sausage (lactobacillus paracasei) on blood lipids and immunological
parameters of healthy volunteers. Food Research International. 35: 133-138.
Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., Okano, M.,
Kagoshima, M., Tsuchida, T. (2010). Regulation of abdominal adiposity by probiotics
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
24
(lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial.
European Journal of Clinical Nutrition. 64: 636-643.
Kailasapathy, K., Chin, J. (2000). Survival and therapeutic potential of probiotic organisms with
reference to lactobacillus acidophilus and bifidobacterium spp. Immunology and Cell Biology.
78: 80-88.
Kianifar, H. R., Farid, R., Ahanchian, H., Jabbari, F., Moghiman, T., Sistanian, A. (2009).
Probiotics in the treatment of acute diarrhea in young children. Iran J Med Sci. 34(3): 204-207.
Klein, A., Friedrich, U., Vogelsang, H., Jahreis, G. (2008). Lactobacillus acidophilus 74-2 and
bifidobacterium animalis subsp. lactis DGCC 420 modulate unspecific cellular immune response
in healthy adults. European Journal of clinical nutrition, 62: 584-593.
Kolida, S., Tuohy, K., Gibson, G. R. (2000). The human gut flora in nutrition and approaches for
its dietary modulation. British Nutrition foundation Nutition Bulletin. 25: 223-231.
Kowalska-Duplaga, K., Fyderek, K., Szajewska, H., Janiak, R. (2004). Efficacy of Trilac® in the
treatment of acute diarrhea in infants and young children-a multicentre, randomized, double-
blind placebo-controlled study. Pediatria Wspóczesna, Gastroenterologia, Hepatologia iywienie
Dziecka. 6(3): 295-299.
Lakka, H. M., Laaksonen, D. E., Lakka, T. A., Niskanen, L. K., Kampusalo, E., Tuomilehto, J.,
Salonen, J. T. (2002). The metabolic syndrome and total and cardiovascular disease mortality in
middle-aged men. JAMA. 288: 2709-2716.
Lebeer, S., Vanderleyden, J., Keersmaecker, S. C. J. (2010). Host interactions of probiotic
bacterial surface molecules: comparison with commensals and pathogens. Nature Reviews
Microbiology. 8: 171-184.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
25
Lee, M. C., Lin, L. H., Hung, K. L., Wu, H. Y. (2001). Oral bacterial therapy promotes recovery
from acute diarrhea in children. Acta Paediatr Taiwan. 42(5): 301-305.
Lei, V., Friis, H., Fleisher Michaelsen, K. (2006). Spontaneously fermented millet product as a
natural probiotic treatment for diarrhea in young children: an intervention study in North Ghana.
International Journal of Food Mcrobiology. 110: 246-253
Levri, K. M., Ketvertis, K., Deramo, M., Merenstein, J. H., Damico, F. (2005). Do probiotics
reduce adult lactose intolerance? The Journal of Family Practice. 54 (7): 613-620.
Lewis, S. J., Burmeister, S. (2005). A double-blind placebo-controlled study of the effects of
lactobacillus acidophilus on plasma lipids. European Journal of Clinical Nutrition. 59: 776-780.
Ley, R. E. (2010). Obesity and the human microbiome. Current Opinion in Gastroenterology.
26: 5-11.
Lourens-Hattingh, A., Viljoen, B. C. (2001). Yogurt as probiotic carrier food. InternationalDairy
Journal. 11: 1-17.
Lye, H. S, Kuan, C. Y, Ewe, J. A, Fung, W. Y, Liong, M. T. (2009). The improvement of
hypertension by probiotics: effects on cholesterol, diabetes, renin and phytoesterogens.
International Journal of Dairy Sciences. 10: 3755-3775.
Mane, J., Pedrosa, E., Loren, V., Gassull, M. A., Espadaler, J., Cune, J., Audivert, S., Bonachera,
M. A., Cabre, E. (2011). A mixture of lactobacillus plantarum CECT 7315 and CECT 7316
enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-
controlled, randomized pilot trial. Nutr Hosp. 26(1): 228-235.
Martinez-Canavate, A., Sierra, S., Lara-Villoslada, F., Romero, J., Maldonado, J., Boza, J., Xaus,
J., Olivares, M. (2009). A probiotic dairy product containing L. gasseri CECT5714 and L.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
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26
coryniformis CECT5711 induces immunological changes in children suffering from allergy.
Pediatr Allergy Immunol. 20: 592-600.
Mcfarland, L. V. (2006). Meta-analysis of probiotics for the prevention of antibiotic associated
diarrhea and the treatment of clostridium difficile disease. Am J of Gastroenterol. 101: 812-822.
Musso, G., Gambino, R., Cassader, M. (2010). Obesity, diabetes and gut microbiota. Diabetes
Care. 33: 2277-2284.
Mustapha, A., Jiang, T., Savaiano, D. A. (1997). Improvement of lactose digestion by humans
following ingestion of unfermented acidophilus milk: influence of bile sensitivity, lactose
transport and acid tolerance of lactobacillus acidophilus. Journal of Dairy Sciences. 80: 1537-
1545.
Naruszewicz, M., Johansson, M. L., Zapolska-Downar, D., Bukowska, H. (2002). Effect of
lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. Am J Clin Nutr.
76: 1249-1255.
Nermes, M., Kantele, J. M., Atosuo, T. J., Salminen, S., Isolauri, E. (2010). Interaction of orally
administered lactobacillus rhamnosus GG with skin and gut microbiota and humoral immunity in
infants with atopic dermatitis. Clinical and Experimental Allergy. 41: 370-377.
Olivares, M., Diaz-Ropero, M. P., Gomez, N., Lara-Villoslada, F., Sierra, S., Maldonado, J. A.,
Martin, R., Rodriguez, J. M., Xaus, J. (2006). The consumption of two new probiotic strains,
lactobacillus gasseri CECT 5714 and lactobacillus coryniformis CECT 5711, boosts the immune
system of healthy humans. International Microbiology. 9: 47-52
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
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27
Ooi, L. G., Liong, M. T. (2010). Cholesterol-lowering effects of probiotics and prebiotics: a
review of in vivo and in vitro findings. International Journal of molecular Sciences. 11: 2499-
2522.
Parra, M. D., Martinez de Morentin, B. E. M., Cobo, J. M., Mateos, A., Martínez, J. A. (2004).
Daily ingestion of fermented milk containing lactobacillus casei DN114001 improves innate-
defense capacity in healthy middle-aged people. J Physiol Biochem. 60(2): 85-91.
Pendone, C. A., Bernabeu, A. O., Postaire, E. R., Bouley, C. F., Reinert, P. (2000). The effect of
supplementation with milk fermented by lactobacillus casei on acute diarrhea in children
attending day care centers. International Journal of Clinical Practice. 53(3): 179-184.
Pickup, J. C. (2004). Inflammation and activated innate immunity in the pathogenesis of type 2
diabetes. Diabetes Care. 27: 813-823.
Rampengan, N. H., Manoppo, J., Warouw, S. M. (2010). Comparison of efficacies between live
and killed probiotics in children with lactose malabsorption. Southern Asian J Trop Med Public
Health. 41(2): 474-481.
Ranadheera, R. D. C. S., Baines, S. K., Adams, M. C. (2010). Importance of food in probiotic
efficacy. Food Research International. 43: 1-7.
Rinne, M., Kalliomaki, M., Arvilommi, H., Salminen, S., Isolauri, E. (2005). Effect of probiotics
and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral
immune responses. J Pediatr. 147: 186-191.
Ritchie, B. K., Brewster, D. R., Tran, C. D, Davidson, G. P, McNeil, Y., Butler, R. N. (2010).
Efficacy of lactobacillus GG in aboriginal children with acute diarrheal disease: a randomized
clinical trial. JPGN. 50: 619-624.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
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Rosenfeldt, V., Michaelsen, K. F., Jakobsen, M., Larsen, C. N., Moller, P. L., Pedersen, P.,
Tvede, M., Weyrehter, H., Valerius, N. H., Paerregaard, A. (2002). Effect of probiotic
lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J.
21(5): 411-416.
Sanz, Y., Santacruz, A., Gauffin, P. (2010). Probiotics in the defense and metabolic balance of
the organism, gut microbiota in obesity and metabolic disorders. Proceedings of the Nutrition
Society. 69: 434-441.
Saraf, K., Shashikanth, M. C., Priya, T., Sultana, N., Chaitanya, N. C. S. K. (2010). Probiotics -
Do they have a role in medicine and dentistry? JAPI. 58: 488-492.
Sarker, S. A., Sultana, S., Fuchs, G. J., Alam, N. H., Azim, T., Brussow, H., Hammarstrom, L.
(2005). Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the
outcome of non rotavirus diarrhea in children from Bangladesh. Pediatrics. 116: 221-228.
Saxelin, M., Lassig, A., Karjalainen, H., Tynkkyen, S., Surakk, A., Vapaatalo, H. (2010).
Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yogurt
or cheese. International Journal of Food Microbiology. 144: 293-300.
Seifert, S., Bub, A., Franz, C. M., Watzl, B. (2011). Probiotic lactobacillus casei Shirota
supplementation does not modulate immunity in healthy men with reduced natural killer cell
activity. J Nutr. 141(5): 978-984.
Sierra, S., Lara-Villoslada, F., Sempere, L., Olivares, M., Boza, J., Xaus, J. (2010). Intestinal and
immunological effects of daily oral administration of lactobacillus salivarius CECT5713 to
healthy adults. Anaerobe. 16: 195-200.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
ACCEPTED MANUSCRIPT
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29
Simons, L. A., Amansec, S. G., Conway, P. (2006). Effect of lactobacillus fermentum on serum
lipids in subjects with elevated serum cholesterol. Nutrition, Metabolism and Cardiovascular
Diseases. 16: 531-535.
Sleator, R. D., Hill, C. (2008). New frontiers in probiotic research. Letters in applied
microbiology. 46: 143-147.
Stadlbauer, V., Mookerjee, R. P., Hodges, S., Wright, G. A. K., Davies, N. A., Jalan, R. (2008).
Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients
with compensated alcoholic cirrhosis. Journal of Hepatology. 48: 945-951.
Szymanski, H., Pejcz, J., Jawien, M., Chmielarczyk, A., Strus, M., Heczko, P. B. (2005).
Treatment of acute infectious diarrhea in infants and children with a mixture of three
lactobacillus rhamnosus strains- a randomized, double-blind, placebo-controlled trial. Aliment
Pharmacol Ther. 23: 247-253.
Trois, L., Cardoso, E. M., Miura, E. (2008). Use of probiotics in HIV-infected children: A
randomized double-blind controlled study. Journal of Tropical Pediatrics. 54(1): 19-24.
Vivatvakin, B., Kowitdamrong, E. (2006). Randomized control trial of live lactobacillus
acidophilus plus bifidobacterium infantis in treatment of infantile acute watery diarrhea. J Med
Assoc Thai. 3: 126-133.
Xiao, J. Z., Kondo, S., Takahashi, N., Miyaji, K., Oshida, K., Hiramatsu, A., Iwatsuki, K.,
Kokubo, S., Hosono, A. (2003). Effects of milk products fermented by bifidobacterium longum
on blood lipids in rats and healthy adult male volunteers. J Dairy Sci. 86: 2452-2461.
Yesovitch, R., Cohen, A., Szilagyi, A. (2004). Failure to improve parameters of lactose
maldigestion using the multi probiotic product VSL3 in lactose maldigesters: a pilot study. Can J
Gastroenterol. 18(2): 83-86.
Downloaded by [Elnaz Vaghef Mehrabany] at 12:58 13 August 2014
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Figure legends
Figure 1) routes through which probiotics may be effective in alleviating diarrhea
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Figure 2) possible mechanisms through which intestinal microbiota can affect body weight
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Figure 3) possible mechanisms for the cholesterol lowering property of probiotics
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Figure 4) possible mechanism through which probiotics induce immune response
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Tables
Table 1) Results from studies on the effect of probiotics on acute diarrhea and lactose
intolerance, performed between 2000 and 2011
Carrier
Type
Species/str
ain
Dose
Health
conditio
n
Effect
Ref.
Food
Yogurt
Yogurt
cultures and
L.casei DN-
114 001
1010
CFU/day
Diarrhea
Incidence of
diarrhea was
significantly
reduced
Pedone
et al.,
2000
Acidifi
ed
formul
a
B. Bifidum
BbF
Not
mentioned
Diarrhea
Less chance
to get
diarrhea
during stay,
later
occurrence of
the episodes
and shorter
duration of
the episodes
were seen for
the probiotic
group
Chouraq
ui et al.,
2004
Millet
Lactic acid
bacteria,
which was
dominated
by W.
confusa and
L.
fermentum
3×1010
CFU/day
Diarrhea
stool
frequency,
stool
consistency
and duration
of diarrhea
were not
affected,
however well
being
increased
Lei et al.,
2006
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Carrier
Type
Species/str
ain
Dose
Health
conditio
n
Effect
Ref.
Supplem
ent
Powder
L.GG ATC
53103
1010
CFU/day
Diarrhea
Shorter
duration of
diarrhea, less
chance of a
protracted
course, and
faster
discharge
from the
hospital were
observed
Guandali
ni et al.,
2000
Capsul
e
L.acidophil
us
B.infantis
109
CFU/day
109
CFU/day
Diarrhea
The duration
of diarrhea
during
hospitalizatio
n in study
group
decreased
Lee et
al., 2001
Capsul
e
L.rhamnosu
s 19070-2
L.ruteri
DSM 12246
21010
CFU/day
21010
CFU/day
Diarrhea
Supplementa
tion reduced
the period of
rotavirus
excretion and
reduced
length of
hospital stay
Rosenfel
dt et al.,
2002
Capsul
e
L.GG
109
CFU/day
Diarrhea
There was no
significant
reduction in
diarrhea
duration
and stool
output in the
L.GG
Costa-
rebeiro et
al., 2003
Capsul
e
L.acidophil
us LaCH-5
1.6109
CFU/day
Diarrhea
Supplementa
tion was only
Kowalsk
a-
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Carrier
Type
Species/str
ain
Dose
Health
conditio
n
Effect
Ref.
B.bifidum
Bb-12
L.bolgaricu
s Lb-Y 27
moderately
effective in
shortening
the
course of
acute
diarrhea
group
Duplaga
et al.,
2004
Powder
L.paracasei
ST11
1010
CFU/day
Diarrhea
Supplementa
tion had a
clinically
significant
benefit
in the
management
of children
with non
rotavirus-
induced
diarrhea, but
it is
ineffective in
those with
rotavirus
diarrhea
Sarker et
al., 2005
Capsul
e
L.Rhamnos
us 573L/1;
573L/2;
573L/3
2.41010
CFU/day
Diarrhea
Supplementa
tion
shortened the
time of
intravenous
rehydration
Szymans
ki et al.,
2006
Capsul
e
Lactobacill
us
B.infantis
3109
CFU/day
Diarrhea
Diarrhea
duration
was
shortened
Vivatvak
in et al.,
2006
Powder
Either of 4
Approximat
Diarrhea
L.GG
Canani et
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Carrier
Type
Species/str
ain
Dose
Health
conditio
n
Effect
Ref.
strains or a
mixture of
four
probiotic
bacteria
ely 109
CFU of
each
reduced the
duration of
the diarrhea
al., 2007
Powder
L.GG
12107
CFU/day
Diarrhea
No effects
were
observed
Basu et
al., 2007
Powder
L.GG
21010
CFU/day
Or
21012
CFU/day
Diarrhea
Duration and
frequency of
diarrhea and
hospital stay
decreased
Basu et
al., 2009
Powder
L.acidophil
us
B.bifidum
109 CFU
109 CFU
(the
combinatio
n
administere
d 3 times
daily)
Diarrhea
The
treatment
decreased
duration and
frequency of
diarrhea and
hospital stay
Kianifar
et al.,
2009
Powder
Bio three
composed
of:
B.mesenteri
cus
E.faecalis
C.butyricu
m
2.5107
CFU/kg/da
y in 3
divided
doses
Diarrhea
The severity
of diarrhea
and hospital
stay
decreased
Chen et
al., 2010
Capsul
e
L.GG
15109
CFU/day
Diarrhea
No effects
were seen
except that
diarrhea
frequency
decreased on
Ritchie et
al., 2010
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Carrier
Type
Species/str
ain
Dose
Health
conditio
n
Effect
Ref.
day 2
Yogurt
+
capsule
L.bolgaricu
s
S.thermophi
lus
B.animalis
B.longum
3.81010CF
U
1.8109CF
U
Lactose
intoleran
ce
Faecal β-
galactosidase
activity
increased
significantly
and symptom
score
decreased
He et al.,
2008
VSL3
capsule
A mixture
of probiotic
bacteria
Either of
450109 or
4450109
CFU
Lactose
intoleran
ce
No effects
were seen
Yesovitc
h et al.,
2004
Capsul
e+
Satch
Lacidophil
Dialac
Not
mentioned
Lactose
intoleran
ce
Breath
hydrogen
decreased
Rampeng
an et al.,
2010
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Table 2) Results from studies on the effects of probiotics on elements of metabolic
syndrome, performed between 2000 and 2011
Carrier
Type
Species/stra
in
Dose
Peri
od
Heath
condition
Effect
Ref.
Food
Ferment
ed milk
L.gasseri
SBT2055
1011
CFU/da
y
12
week
s
Obesity
Abdominal,
visceral and
subcutaneou
s fat areas
significantly
decreased
Kadooka
et al.,
2010
Yogurt
L.acidophilu
s LA-5
B.lactis
Bb12
1109
CFU/da
y
9108
CFU/da
y
8
week
s
Diabetes
The
treatment
reduced
LDL-
cholesterol
Ejtahed et
al., 2010;
Ejtahed et
al.,
2011a;
Ejtahed et
al., 2011b
Yogurt
(NY-
YP901)
A mixture of
probiotic
bacteria plus
functional
ingredients
Differe
nt doses
for the
bacteria
8
week
s
Metabolic
syndrome
The
treatment
significantly
decreased
total and
LDL
cholesterol
as well as
body weight
and BMI
Chang et
al., 2011
Proviva
(drink)
L.plantarum
299v (DSM
9843)
21010
CFU/da
y
6
week
s
Hypertensio
n
Systolic
blood
pressure,
leptin and
fibrinogen
decreased
significantly
Naruszew
icz et al.,
2002
Powder
ed
L.helveticus
CM4
Not
mention
4
week
Hypertensio
n
Intervention
decreased
Aihara et
al., 2005
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Carrier
Type
Species/stra
in
Dose
Peri
od
Heath
condition
Effect
Ref.
ferment
ed milk
(tablets)
ed
s
diastolic
blood
pressure
significantly
Sausage
L.paracasei
LTH 2579
5109
CFU/da
y
5
week
s
Hyper-
cholesterole
mia
No effects
were
observed in
lipid profile,
a
significantly
higher titer
of antibodies
against
oxidized
LDL was
observed
Jahreis et
al., 2002
Milk
B.longum
BL1
91010
CFU/da
y
4
week
s
Hyper-
cholesterole
mia
Total
cholesterol
decreased
particularly
in those with
mild hyper-
cholesterole
mia
Xiao et
al., 2003
Yogurt
L.acidophilu
s
B.lactis
3108
CFU/da
y
6
week
s
Hyper-
cholesterole
mia
Only total
cholesterol
decreased
significantly
Ataie-
Jafari et
al., 2009
Supplem
ent
Capsule
L.acidophilu
s NCFM
1010
CFU/g
4
week
s
Diabetes
Supplementa
tion
preserved
insulin
sensitivity
but did not
affect
systemic
inflammator
Andrease
n at al.,
2010
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Carrier
Type
Species/stra
in
Dose
Peri
od
Heath
condition
Effect
Ref.
y responses
Capsule
L.acidophilu
s LA-1
61010
CFU/da
y
6
week
s
Hyper-
cholesterole
mia
Cholesterol
was
decreased in
vitro, but
throughout
the study no
changes
were
observed
Lewis &
Burmeist
er., 2005
Capsule
PCC®
L.fermentum
4109
CFU/da
y
10
week
s
Hyper-
cholesterole
mia
No effects
were seen
Simons et
al., 2006
Capsule
L.rhamnosu
s LC705
P.freudenrei
chii
ssp
shermanii
JS
41010
CFU/da
y
4
week
s
Hyper-
cholesterole
mia
No effects
were seen
Hatakka
et al.,
2008
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Table 3) Results from studies on the effects of probiotics on immune system function,
performed between 2000 and 2011
Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
Food
Milk
B.lactis
HN019
5109
CFU/da
y
Or
51010
CFU/da
y
3
weeks
Immunity
of elderly
subjects
Increased
CD4+,
CD25+,
natural killer
cells and
phagocytic
capacity of
immune cells
were seen
Gill et
al., 2001
Fermente
d milk
L.casei
DN114001
108-1010
CFU/da
y
8
weeks
Immunity
of healthy
subjects
No changes
in immune
cell
proportions
were
detected but
oxidative
burst
capacity of
monocytes
and NK cells
tumoricidal
activity
increased
Parra et
al., 2004
Formula
B.animalis
Bb-12
6109
CFU/10
0 ml
32
weeks
Immunity
of non-
breastfed
newborns
No effects
on fecal
SIgA were
observed
Bakker-
Zierikzee
et al.,
2006
Fermente
d
product
L.gasseri
CECT
5714 and
L.corynifor
mis CECT
5711
Not
mention
ed
4
weeks
healthy
adult
human
volunteers
The
treatment
induced an
increase in
the
proportion of
Olivares
et al.,
2006
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Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
natural killer
(NK) cells
and
in IgA
concentratio
ns which
suggests
regulation of
the immune
system
Yogurt
L.acidophil
us 74-2
B.lactis
subsp lactis
DGCC 420
27.910
10
CFU/da
y
9108
CFU/da
y
5
weeks
Immunity
of healthy
subjects
Percentages
of
granulocytes
and
monocytes
showing
phagocytic
activity were
significantly
elevated
Klein et
al., 2008
Formula
B.bifidum
S.thermophi
lus
2.5101
0
CFU/da
y
8
weeks
Immunity
of HIV
infected
children
There was an
increase in
the mean
CD4 count
Trois et
al., 2008
Yogurt
L.gasseri
CECT5714
L.corynifor
mis
CECT5711
2108
CFU/da
y
2108
CFU/da
y
12
weeks
Immunity
of allergic
children
Serum IgE
decreased
and
regulatory T
cells and
natural killer
cells
increased
Martinez
-
Canavate
et al.,
2009
Milk
L.casei
Shirota
1.9510
10
CFU/da
y
4
weeks
Immunity
of healthy
men with
a reduced
NK lytic
Intervention
didn’t
increase NK
cell activity
in healthy
Seifert et
al., 2011
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Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
function
men
Extensiv
ely
hydrolys
ed casein
formula
L.rhamnosu
s GG
(ATCC
53103)
3.4109
CFU/da
y
12
weeks
Immunity
of infants
with
atopic
dermatitis
IgA and IgM
secreting
cells
decreased
and CD19(+)
CD27(+) B
cells
increased
Nermes
et al.,
2011
Powdere
d
skimmed
milk
L.plantaru
m CECT
7315 and
CECT 7316
Either
of
5108
CFU/da
y
Or
5109
CFU/da
y
12
weeks
Immunity
of elderly
subjects
Depending
on the dose,
L. plantarum
has different
immune-
enhancing
effects in
elderly
subjects
Mane et
al., 2011
Supplem
ent
Suspensi
on
E.coli
Nissle 1917
1 ml at
a time
5 days
and
three
times a
week
for 3
more
weeks
Immunity
of
premature
infants
Significantly
higher
amounts of
specific anti-
E. coli Nissle
1917
antibodies
(Ab) of
immunoglob
ulin (Ig)A
isotype and
nonspecific
polyclonal
IgM were
found in the
blood of
colonized
infants
Cukrows
ka et al.,
2002
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Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
Tablet
L.gasseri
PA 16/8
B.longum
SP 07/3
B.bifidum
MF
20/5
5107
CFU/da
y
12
weeks
Immunity
of healthy
subjects
Symptoms
and duration
of cold
decreased.
Sytotoxic T
cells and
suppressive
T cells and
helper T
cells were
enhanced
De Vrese
et al.,
2005
Capsule
L.rhamnosu
s GG
(ATCC
53103)
1010
CFU/da
y
4
weeks
before
expect
ed
deliver
y
and 6
month
s to
the
infants
Gut
microecol
ogy and
Immunity
of infants
(Ig)G-
secreting
cells in
Probiotic
group
exceeded the
placebo
group which
correlated
with
concentratio
n of sCD14
in colostrum
Rinne et
al., 2005
Capsule
B.lactis ssp.
lactis (BB-
12)
L.paracasei
ssp.
paracasei
(CRL-431)
108,
109,
1010, or
1011
CFU/da
y
3
weeks
Immunity
of healthy
subjects
No effects
were
observed
Christens
en et al.,
2006
Capsule
L.casei
Shirota
19.510
9
CFU/da
y
4
weeks
Immunity
in cirrhotic
patients
The
treatment
restored
neutrophil
phagocytic
capacity,
possibly by
Stadlbau
er et al.,
2008
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Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
changing
IL10
secretion and
TLR4
expression
Capsule
L.coagulan
s GBI-30
2109
CFU
4
weeks
Immunity
in healthy
adults
The
treatment
significantly
increased T-
cell
production
of TNF-α in
response to
adenovirus
exposure and
influenza A
exposure,
but it did not
have a
significant
effect on the
response to
other strains
of influenza
Baron,
2009
Powder
B.mesenteri
cus
E.faecalis
C.butyricu
m
3107
CFU/da
y
7 days
Immunity
of children
IL-10 was
increased in
the serum
and
supernatants
of cell
culture and
tumor
necrosis
factor alpha
values were
down-
regulated.
Interferon
gamma and
Chen et
al., 2010
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Carrier
Type
Species/str
ain
Dose
Period
Health
condition
Effect
Ref.
IL-12 were
mildly
elevated in
the
probiotics
group
Capsule
L.salvarius
CECT5713
2108
CFU/da
y
4
weeks
Immunity
of healthy
adults
Percentage
of NK cells
and
monocytes,
as well as the
plasmatic
levels of
immuno-
globulins M,
A and G, and
the
regulatory
cytokine IL-
10
Sierra et
al., 2010
Capsule
L.plantaru
m HEAL 9
L.paracasei
8700:2
109
CFU/da
y
12
weeks
Immunity
of healthy
subjects
The risk of
acquiring
common
cold
infections
was
decreased
Berggren
et al.,
2011
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... The assessment of the host microbiome is obtaining consideration with augmenting resources being devoted to pivotal and translational investigation in the field of microbiomebased therapeutics. These exertions have been positively translated to the clinic, and the investigation/treatment of the host microbiome is currently known as a novel biotherapeutic strategy in the way of enhancing host health status and well-being (Homayoni Rad et al. 2016;Pourakbari et al. 2020). For instance, imbalance in the gut microbial composition is currently deliberated as a significant predisposing element for an extensive range of metabolic syndromes, leading to the rising use of biotherapeutic agents such as prebiotic/probiotic compounds as daily diet supplementation (Guo et al. 2021;Rad 2013;Reid 2002;Salehi et al. 2021) (Figure 1). ...
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... The need for a specific and impressive amount of postbiotic to have a known beneficial clinical effect is a fundamental challenge. Other challenges include preventing adverse interactions of postbiotics with other food matrix compounds, limiting the breakdown of the additive component (postbiotic) under food processing conditions, stabilizing the additive component during the storage, and ensuring that the final product contains a sufficient amount of postbiotic components and provides the desired health effect after digestion [493]. ...
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For centuries, people around the world have used fermentation to preserve and enhance the flavor of a wide variety of foods. Today, complex interactions of microbiota in the digestive tract are found to influence proper digestion, metabolism, and disease resistance. With greater emphasis on natural products and the role of food in health and wellbeing, food manufacturers are once again turning to fermentation not just for extending shelf life, but to create functional food products that take an active part in maintaining overall health. Featuring five new chapters and updating all data to reflect the latest research findings, Handbook of Fermented Functional Foods, Second Edition examines the health benefits of fermented foods as well as the processes and production techniques involved in manufacturing fermented food products. Maintaining the highest quality information and the easily accessible format of its predecessor, this edition includes new chapters on olives, tempeh, and the traditional fermented foods of China, Thailand, and India. It looks at the history of fermented foods and reveals the specific benefits of fermented milk, Kefir, yogurt, and cheese. Contributions cover fermented soy products, including Natto and Miso, as well as the fermentation of other vegetables such as Korean Kimchi and Doenjang and German sauerkraut. The book also explains the bioactivity and bioavailability of microorganisms and investigates the more recent practice of producing probiotic cultures to add to fermented foods for increased health benefit. Presenting new findings and interpretations that point even more clearly to the important role fermented foods play in our diet and overall health, this second edition demonstrates the current knowledge of fermented food production and reflects the growing credibility of probiotics in health maintenance.
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