According to the United Nations Development Programme report in 2010, many developing countries in Africa, Southeast Asia and the Middle East are considered to have a gross income and a quality of life index below average [1]. People in developing countries not only suffer from malnutrition but also from enteric infections due to weakened immunity and lack of proper hygiene, sanitation, clean drinking water and access to proper medical care [2,3]. Every year more than a million children in these regions suffer and die from diarrhea alone [1].

Advances in the field of medicine and public health during the last decades have increased the survival rate of children in their early life; however, every 15 seconds one child still dies from diarrheal disease mostly associated with contaminated food, water or HIV/AIDS [4]. It was also found that out of approximately 8.795 million deaths in the world among children below 5 years of age, 68% was due to infectious diseases, with 49% of these deaths taking place in developing countries such as India, Nigeria, Democratic Republic of Congo, Pakistan and China [5]. The World Health Organization (WHO) also predicts that by 2025 there will still be around 5 million deaths among children below 5 years of age and 97% of these deaths will be in developing countries [6]. In addition to these major problems; there are other nutritional related disorders such as lactose intolerance or high cholesterol levels that affect people in developing countries. Therefore, urgent and sustainable measures are required to be undertaken by developing nations to improve the health of their people [4]. Probiotic interventions could provide an invaluable opportunity to ameliorate this current situation. This review will thus outline the potential health benefits of probiotics, and will examine the rationale for the introduction of probiotics into the developing world with particular attention to probiotic dairy products.

Probiotics have been defined as “live microorganisms which when administered in adequate amounts confer a health benefit to the host” [7]. This definition applies only to products containing live microorganisms, and requires an adequate dose of microorganisms in order to exert the desirable effect [8]. Also the probiotic bacteria should remain viable during preparation, use and storage of the food product and it must be able to survive the intestinal environment to benefit the host [9].

The scientific basis for the use of live microbes in the prevention and treatment of infections dates back to over 100 years, when the Russian scientist Elie Metchnikoff in 1907 hypothesized that bowel health and prolongation of life could be possible by replacing or reducing the number of ‘putrefactive’ bacteria in the gut with lactic acid bacteria [10]. Gut microbiota has been defined as an organ composed of atleast 10¹³ microorganisms and mainly dominated by anaerobic microorganisms comprising of approximately 500-1000 different species that have evolved to perform functions such as digestion of indigestible fraction of food and are required to maintain good health [11]. In the last three decades, research in probiotics has advanced tremendously resulting in selection and characterization of specific probiotic cultures and the evaluation of health benefits attributed to their continuous consumption. Furthermore, advances in molecular techniques allows the possibility of tracking changes in gut microbiota after consumption of probiotic and prebiotic products and thus enabling a better understanding of their function and potential for the prevention and management of infectious diseases and gastrointestinal disorders.

Developed and developing countries differ in their perspectives regarding probiotics. In developed countries, probiotic foods are considered revolutionary and are viewed as a means for maintaining a balanced gut flora and gut health. In developing countries however, probiotics are still in question and are a dilemma for scientists, clinicians and consumers [12]. This might be in part due to lack of product availability because of limited infrastructure and funding for this area of research [1].

The criteria for the selection of probiotic strains for human consumption depends on safety, functionality and technological aspects. The safety aspect suggests that the isolated strains should preferably be of human origin, isolated from healthy human gastrointestinal (GI) tract, non-pathogenic, have no history of association with infective diseases, do not deconjugate bile salts, and do not carry antibiotic resistance genes [13]. However, origin of the strain is not as important as viability at the target site [8]. Functional properties include acid tolerance to survive digestion, bile tolerance to survive in the small bowel, adherence, colonization and persistence in the GI-tract, viability at the target site, immune stimulation, antigenotoxic activity and inhibition of pathogens [13]. Technological aspects include the ability to be manufactured under industrial conditions, heat tolerance, survival and retention of their functionality during storage, sensory properties, and phage resistance [13,14]. Technological and sensory properties such as taste, texture, appearance and palatability of probiotic food are specifically important because by satisfying consumer demands, the food industry will succeed in promoting and encouraging the consumption of functional probiotic products [13].

Probiotic bacteria have been increasingly included in yogurts and other cultured milk products during the past three decades as a result of perceived health benefits. Members of the genera Lactobacillus and Bifidobacterium are the principle probiotic microorganisms generally used though not exclusively [8]. A summary of identified probiotic bacteria and yeast strains are presented in (Table 1). The conditions that need to be met for probiotic microorganisms to achieve their potential health bene?ts include being delivered at a high dose through food vehicles (especially dairy products such as yogurt, cheese, and ice cream); and being able to remain viable when they reach the intestine. The food industry and the United States Food and Drug Administration (US FDA) have adopted the minimum viable probiotic count of 10⁶ CFU (Colony Forming Units)/mL at the time of consumption of probiotic foods. This standard appears to have technical and cost associated benefits [14]. A regular intake of 10⁸ to 10⁹ CFU/day of probiotic microorganisms is required for the probiotics to exert their health bene?ts [14,15]. This might vary depending on the best-before date and the amount of probiotic food ingested [14]. In addition, repeated administration of probiotic bacteria ensures adequate population levels over time [16]. These bacteria play an important role in digestion of complex polysaccharides that help in production of short chain fatty acids that serves as a source of energy for colonocytes. Also they are able to protect us from a load of external microbes due to colonization resistance that they offer by displacing gas-producing and bile salt deconjugating bacterial species. The probiotics maintain this barrier function by the production of antimicrobial peptides, immunoglobulin A and by acidification of the colon. Beyond these beneficial properties they are also involved in synthesis of vitamins such as folate, vitamin K and biotin, biotransformation of drugs and xenobiotics and metabolism of bile acids [17,18].

Table 1: Probiotic bacteria and yeast shown to exert health beneficial effects [10].

At present, over 70 probiotic products are available all over the world commercially and include dairy products such as sour cream, ice cream, buttermilk, yogurt, milk powder and frozen desserts containing Bifidobacteria and Lactobacilli [14]. However it has been reported that viable Bifidobacteria counts in fermented milk products may reduce rapidly unless specific attention is given to strain selection and pH [19]. Also, it has been reported that fermented foods cannot be termed as probiotic food because there is no evidence supporting the fact that, if only the bacteria in the food is beneficial or there is also contribution of the food matrix. Also, in fermented foods, bacteria are part of a diverse community that is not well-defined in terms of strain composition and stability [7]. The incorporation of probiotic strains into cheese might be an encouraging alternative to the Bifidobacteria survival problem in acidic products such as yogurt and cultured butter milk. Cheese's closed matrix and low acidity, in addition to the high fat content may protect these strains during cheese manufacturing, storage and passage through the gastrointestinal tract [20]. Research has also shown potential to incorporate probiotics in non-dairy foods such as soy milk, soy cream cheese, chocolate and variety of juices such as tomato, orange, grape, carrot, beet and cabbage juice [14,21]. Probiotics are also available in the form of capsules, tablets and powders. [10,14]. Overall the incorporation of probiotics in foods and their survival ability depends on the food matrix, composition, pH, storage facilities, thus making it a challenge for manufacturers.

Considering that most frequent health issues in developing countries are related to intestinal health, the intervention with probiotics would greatly benefit the health of populations in these nations. Probiotics would be able to do so through their inhibitory actions against pathogens and parasites, their ability to reduce antibiotic associated diarrhea and to protect against acute and infectious diarrhea. Other benefits include protection against HIV/AIDS infection, alleviation of lactose intolerance symptoms, lowering of cholesterol levels, improvement of overall nutritional status of people in developing regions, alleviation of allergies and ability to serve as a vaccine adjuvant.

Inhibition of pathogenic microbes and parasites

Probiotic strains have been shown to inhibit the growth, metabolic activity, and adhesion of enteropathogenic Salmonella, Shigella, enterotoxigenic Escherichia coli, or Vibrio cholerae to intestinal cells, thus helping to regulate intestinal microflora and exert immunostimulatory effects [22]. Suggested mechanisms involve competition for fermentable substrates, the pH lowering effect in the intestine, the production of bactericidal acids such as lactic, acetic, hippuric, butyric and citric acids [21,22], the production of H2O2 and the agglutination of pathogenic microorganisms inhibiting their growth [22-24]. In addition, protective functions to the host are mediated by degradation of arginine with production of nitric oxide (NO), which has shown to protect the lower intestinal tract [25] as well as the binding and metabolism of toxic metabolites (Aflatoxin M1) and aflatoxin B1 by strains of Lactobacilli, Lactococcus and Bifidobacterium which make them unavailable for absorption in the intestinal tract [26,27]. Due to various anti-microbial actions, a combination of probiotics have been found to be beneficial. Colonization of E.coli O157: H7 was found to be reduced by consumption of L.casei Shirota strain [28] and Salmonella enteritidis was completely eliminated by consumption of L. salivarius [29]. In a study on pigs, levels of Salmonella typhimurium was reduced by using a mixture of strains L. murinus, L. salvarius subspp. Salivarius, L. pentosus and Pedicoccus pentosaceous as compared to animals treated with skim milk without probiotics [30].

Helicobacter pylori is another gram negative pathogen that was found to cause peptic ulcers, gastric cancer and type B gastritis and its infection is common in developing countries due to lack of proper hygiene, sanitation and safe drinking water [31]. Various lactic acid bacteria such as L. johnsonii La1 have proven to be effective against this pathogen (tested in 20 adults with mean age of 33 years) and the hypothesized mechanism is the probiotic induced decrease of urease enzyme activity which is required for their sustenance in the acidic environment of the stomach [8,32]. Other human studies have also shown reduction in H. pylori infection by treatment with L. brevis lyophilized bacteria or yogurts containing L. acidophilus, B. lactis and L. gasseri [33]. Moreover, the incidents of side effects produced by the use of antibiotics used to treat H. pylori infection was reduced by half when using a combination therapy of antibiotics and probiotics [33]. However few studies showed controversial evidence about the beneficial effects of probiotics in treatment against H. pylori infection and hence long term studies on the specific strain, doses and administration are required [34,35].

Other therapeutic approaches, of high relevance for developing countries, are the reduction of parasite infections by the use of specific probiotic strains. As reviewed by Marie-Agn`es Travers et al. [36], it was found that the administration of L. reuteri 4000 to mice, 7-15 days before infection with Cryptosporidium parvum bought about a 50-100% reduction in the parasite infection and the probiotics L. acidophilus NCFM, B. breve ATCC15698 or B. longum ATCC15707, B. brevis, E. faecium and P. alcaligenes showed similar reduction in Cryptosporidium parvum infection in cell culture models. Furthermore, L. johnsonii La 1, L. casei and Enterococcus faecium showed 75-100% reduction in Giardia lamblia infection in cell culture and mouse models and the probiotic L. casei was effective in reduction of Babesia microti, Plasmodium chabaudi, Trichinella spiralis and Trypanosoma cruzi infections in mouse models [36]. More studies and human clinical trials from developing countries are needed to demonstrate the benefits of probiotics as an anti-parasite therapeutic alternative.

Reduction of Antibiotic Associated Diarrhea (AAD)

AAD occurs in 5-35% of patients under antibiotic therapy and rates vary according to the specific antibiotic, host health and exposure to pathogens [37]. Antibiotic therapy affects the fecal microflora and causes disturbance of GI micro-ecology leading to loss of colonization resistance. Colonization resistance is defined as the capacity of colon microorganisms to resist influx of external microorganisms. The mechanisms associated with colonization resistance are based on host factors such as bile acids, gastrointestinal proteases, motility, competition for adhesion sites and nutrients with production of toxic metabolites and antagonistic compounds [38]. The use of antibiotics leads to the break down of the colonization defense systems leading to increased infections in individuals by opportunistic pathogens such as Clostridum difficile [38,39]. C. difficile invasion occurs mainly due to antibiotic therapy, but other risk factors include ageing and hospitalization [40]. Moreover, the C. difficile associated diarrhea is responsible for around 10–20% of all cases of AAD and can occur even after 6-8 weeks of antibiotic therapy termination [39,40]. There is evidence that probiotic bacteria and yeast can be effective in preventing AAD and the recurrence of C. difficile infection in both children and adults. [41].

Some of the probiotics most commonly used to prevent AAD are Lactobacillus rhamnosus GG (LGG), Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium spp., Streptococcus spp., and the yeast Saccharomyces boulardii [39]. Other strains and mixtures of strains including L. acidophilus combined with Bifidobacterium infantis, L. sporogens, Bifidobacterium lactis combined with Streptococcus thermophiles, Enterococcus faecium SF 68, Bacillus clausii, Clostridium butyricum seem to be effective as well [39,42]. A study reported that the two most effective strains in preventing AAD and C. difficile infections are LGG and S. boulardii, which are generally considered safe and well tolerated [43]. The risk of developing C. difficile infection in hospitalized patients reduced significantly after consumption of yogurt with L.casei DN-114 001, S. thermophiles and L. bulgaricus [44]. In addition, the effects of L. plantarum intake showed to have a preventive effect on milder gastrointestinal symptoms such as nausea and watery stools during treatment with antibiotics [45].

Another strategy to combat C. difficile infection might be the use of the technique faecal microbiota transplants (FMT). Few studies have shown that FMT decreased the percentage of C. difficile associated diarrhea [46,47]. Also, when another route of delivery of these microbes in the form of feces filled pills were given to 31 patients, it was found to cure 30 patients [47]. But this technique is expensive and far from the visual of commercialization [47]. Also, FMT is not recognized within the banner of probiotics as its procedure is not standardized and its safety is also questioned because of the unknown nature of the FMT mixture in terms of taxa including bacteria, yeasts, parasites and viruses and which microbes are bringing about the beneficial effects [7].

In general, the use of probiotic dairy products containing selected probiotic strains might be an alternative to ameliorate or prevent AAD. The growing use of antibiotics in the developing world will lead to emergence of antibiotic resistant microorganisms and probiotic foods might provide a good solution to this anticipated problem. But still, more well-designed studies are needed to demonstrate the scientific basis for the protective role of probiotics against AAD and encourage their consumption to help improve public health.

Effect of probiotics in acute and infectious diarrhea

The two major conditions responsible for morbidity and mortality in the developing world are diarrhea and HIV/AIDS [4]. Bacterial and viral pathogens are the main causes of these infections and their transmission occurs mainly through contaminated food or drinking water [48]. Estimates in 2008 suggested that diarrhea still caused 1.336 million deaths per year in children younger than 5 years of age [5] with highest rates in some countries of south Asia and Africa (Figure 1). Irrespective of the improved understanding of the pathogenesis of diarrhea and use of oral rehydration therapy (ORT), approximately 2.5 million children still die every year from acute diarrhea in developing countries [3]. It is of paramount importance that this high rate of mortality be reduced to achieve the goal set by United Nations Millennium Development goal 4 between 1990 and 2015 to bring about a two-thirds decrease in child mortality rate [48]. Probiotics can potentially help to reduce these problems. Lactobacillus spp. such as Lactobacillus rhamnosus GG (LGG), Lactobacillus reuteri and Lactobacillus casei, Streptococcus thermophilus, Bifidobacterium bifidum, and S. boulardii have been shown to be promising probiotic strains in treating diarrheal diseases in children [49]. Nonfood probiotics such as E. coli strain Nissle 1917, Enterococcus faecium SF68 and Saccharomyces boulardii in the form of powder suspensions or oral rehydration therapy were also found to be a solution in the treatment of diarrhea [22].

Figure 1: Rates of diarrheal deaths in children. Data is based on 10.4 million children below 5 years of age.

A study reported that administration of LGG in 6-24 month old children in Peru decreased the incidence of diarrhea as compared to the placebo group [50]. LGG was also shown to significantly reduce the mean duration of diarrhea (5.3 days as compared to 9.2 days in control) and stool frequency from day 4 in Indian children suffering from diarrhea [51]. L. casei DN-114001 strain also reduced cases of diarrheal morbidity in children from India by 40% [52]. Another study in Israel reported that healthy infants of 4-10 months of age fed with B. lactis BB-12 and L. reuteri showed reduced episodes of diarrhea as compared with control group [53]. Children between ages of 3 to 10 years from Myanmar showed reduction in the duration of diarrhea by 1.6 days when given S. boulardii in combination with ORT as compared to ORT alone [54]. Similar results were found in a study conducted in Pakistan with 100 children aged between 2-12 months wherein the duration of diarrhea was 3.5 days in children given S. boulardii in combination with ORT as opposed to 4.8 days with only ORT [55].

Rotavirus is a common cause of diarrhea and was found to affect 1 in 1.6 children under 5 years of age and the disease caused death of usually 1 in 375 in Peru [4]. The preventive and curative effects of LGG and B. lactis BB-12 against acute diarrhea mainly caused by rotaviruses in children has been well established by clinical studies [8,22]. Also, diarrhea caused by E. coli is common in developing countries especially amongst children. It was found that milk fermented with starter cultures Streptococcus thermophilus, L. bulgaricus and L. acidophilus produced higher levels of lactic acid and diacetyl whereas milk fermented with L. acidophilus produced the highest amount of hydrogen peroxide showing that milk fermented with the starter cultures was able to cure diarrhea caused by E. coli more effectively due to production of higher levels of antibacterial metabolites [56].

A meta-analysis study comprising of 63 trials with 8014 people mainly infants and children, showed that probiotics shortened the duration of acute infectious diarrhea by 25 hours, showed a 59% reduction in diarrhea lasting for more than 4 days and lesser diarrheal stool on day 2 after intervention [57]. In another study assessing community acquired diarrhea in children, 8 studies showed that diarrhea duration was reduced by 14% and stool frequency on second day treatment was reduced by 13.1% [58].

In general, most of the positive studies demonstrating alleviation and prevention of infectious diarrhea have been performed in infants and children. Young children respond well to probiotics probably because of the immaturity of their immune system and the greater simplicity of their intestinal microflora compared to that of adults [22]. In adults there have been conflicting studies associated with probiotics and infectious diarrhea. Hence the use of probiotics as a treatment for acute and infectious diarrhea in adults, children and against diarrhea caused by other pathogens still needs to be thoroughly researched.

HIV/AIDS prevention

HIV/AIDS is very common in developing countries among women and children, especially in rural areas [4]. Globally, around 14,000 people mostly living in developing countries are in contact with HIV every day, out of which over 7000 women become infected [2,4]. It was found that one of the causes of developing HIV is the lack of Lactobacilli in the vagina and increased number of anaerobic organisms leading to bacterial vaginosis [59]. Hence, increasing the levels of probiotic Lactobacilli has been hypothesized to help prevent HIV infection. In a study on 64 women aged between 19-46 years of age it was found that oral consumption of two probiotic strains L. rhamnosus GR-1 and L. reuteri RC-14 led to significant increase in vaginal Lactobacilli levels as compared to placebo group after 60 days [60]. It was found that at a dose level of at least 10⁸ CFU/day for 2 months, oral consumption of L. acidophilus, L. rhamnosus GR-1 and L. fermentum RC-14 showed an increase in probiotic levels in the vaginal tract of women suffering from bacterial vaginosis [61,62]. Additionally, an observational study over a period of three years reported that probiotic yogurt consumption, supplemented with Lactobacillus rhamnosus, was associated with a significant increase of CD4 among people living with HIV/AIDS [63]. CD4 cells are white blood cells that are a measure of good immune system; these cells are attacked by HIV infection which results in reduction of cell count. In another study it was found that consumption of probiotic yogurt supplemented with Lactobacillus rhamnosus GR-1 by consumers suffering from HIV/AIDS helped in their weight gain, they had significantly higher levels of vitamins and minerals, fewer fungal infections, fewer episodes of diarrhea and lower fatigue levels as compared to people not consuming the probiotic yogurt [64]. Also, a novel research reported that L. jensenii can bind to HIV type 1 (HIV-1) gp12, thus preventing the virus from causing infection [65]. Engineered probiotic strains of E. coli and Streptococcus gordoni producing HIV-gp41-haemolysin and cyanovirin-N have been found to block or inactivate HIV, thus preventing the infection [2]. Overall, the use of probiotics against HIV requires more research, but has not shown any adverse effects [4,61].

Improvement of lactose intolerance symptoms

Lactose intolerance is caused by the deficiency or decreased activity of the lactose-cleaving enzyme ß-galactosidase in the small intestine [66]. It affects more than 75% of the population worldwide and causes flatulence or diarrhea [67,68]. The decreased lactase activity ranges from nearly 5% in northern Europe to more than 90% in some Asian and African countries [68]. Lactose intolerance may lead to deficiencies in the intake of protein, calcium, and other important nutrients in populations from developing countries. This problem might be alleviated by the consumption of fermented dairy products due to their lower lactose content and the release of ß-galactosidase in the GI tract by live probiotic bacteria that can survive digestion [67]. Yogurt was shown to be unique among other fermented milk products such as buttermilk and sweet acidophilus milk. It is well tolerated by lactose intolerant people and enhances lactose digestion in lactase-deficient subjects due to the presence of bacteria such as Lactobacillus bulgaricus and Streptococcus thermophilus which release ß-galactosidase in the intestine [67,69]. However pasteurization of yogurt eliminates this effect due to the reduction in the ß-galactosidase activity [67,69]. A clinical human study showed that supplementation with Bifidobacterium longum capsules and yogurt enriched with Bifidobacterium animalis was effective in alleviating lactose intolerant symptoms [70]. A related study in lactose maldigesting children (5-16 years) demonstrated that consumption of milk with Lactobacillus acidophilus or a commercial yogurt containing Lactobacillus lactis and Streptococcus thermophilus reduced lactose intolerance symptoms compared with the group of children who consumed unfermented milk [67]. A study reported that lactose content decreased to 2.3 g/100 g after 11 days of storage as compared to non-fermented milk containing 4.8 g/100 g. Other fermented products such as buttermilk, kefir and ropy milk also had a 20-26% reduction in lactose content [71]. However, results showing no effects on alleviation of lactose intolerance by probiotic supplementation have also been reported [72]. These controversial results are probably due to differences in specific probiotic strains, concentrations, and preparations, as well as due to the subject’s susceptibility to gas, osmotic pressure or the individual responsiveness to probiotics. Further clinical trials of specific strains and concentrations are necessary to delineate the potential therapeutic effects of probiotics in lactose intolerance [66,72] .

Lowering blood cholesterol levels

Many animal and human clinical trials have shown a relationship between cholesterol levels and increased risk of coronary heart disease. Dairy fermented products with probiotics, especially Bifidobacterium spp. and Lactobacillus spp., have the potential to help reduce serum cholesterol levels [23]. Possible mechanisms involved in the cholesterol-lowering effect of probiotics include assimilation of cholesterol by probiotic bacteria, cholesterol binding to cellular surface and incorporation into the cellular membrane, co-precipitation of cholesterol with probiotic-deconjugated bile that leads to inhibition of intestinal cholesterol absorption, inhibition of bile acid reabsorption, and production of short-chain fatty acids [23,73]. L. acidophilus showed cholesterol lowering properties most likely by assimilating cholesterol in the cells or by its attachment to the cells [74]. In a study performed in India, it was found that consumption of buffalo milk fermented with L. acidophilus showed a 12-20% reduction in serum cholesterol [75]. In another study in adults, consumption of E. faecium M-74 capsules enriched with selenium reduced total serum cholesterol by 12% after 56 weeks [76]. In a study on rats, administration of L. reuteri for 7 days was found to decrease total cholesterol and triglyceride levels by 38% and 40% respectively and increase HDL to LDL cholesterol ratio by 20% [77]. Pereira et al., also showed that Lactobacillus fermentum KC5b strain which was isolated from the human gut, removed 14.8 mg of cholesterol per gram of cells (dry weight) in culture medium [78]. In general, more human studies are required in developing countries to prove the effects of probiotics in lowering blood cholesterol levels [79].

Nutritional Effect

Microorganisms in fermented foods or in the gut have shown to improve the quantity, bioavailability and digestibility of some dietary nutrients [49]. Lactic acid produced during food fermentation by lactic acid bacteria leads to pH reduction, improvement of protein digestibility and calcium absorption. In addition, lactic acid bacteria was also shown to increase folic acid, niacin, and riboflavin levels in cultured dairy products with release of various enzymes and vitamins into the intestinal lumen [49].

Milk and milk products are a good source of minerals especially calcium and phosphorus, but are a poor source of iron.. Although calcium might reduce iron absorption, several studies have demonstrated the efficacy of fermented dairy products as vehicles for iron fortification. In a study it was found that there was a direct correlation between iron intake and the increase of hemoglobin levels when preschool children aged between 2-5 years old were fed with a fermented milk fortified with iron containing amino acid chelate and supplemented with probiotic Lactobacillus acidophilus [80]. Moreover, the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has considered the supplementation of infant formula with probiotics and/or prebiotics as an important area of research. However, more clinical studies are needed to recommend the routine use of probiotics and/or prebiotics in infant formulae [81].

Role of probiotics in allergic disease prevention

Allergic diseases such as eczema, food allergy and asthma have increased in occurrence during the past few decades especially in developed countries [82,83] with nearly 20% of the world population currently affected [84]. This might also be a health concern for developing countries in the near future and probiotics could be used as a strategy in its prevention. The major populations at risk to develop allergic diseases are infants and children due to decreased microbial exposure which results in reduced microbial stimulation in the immune system at an early age [83]. In an allergic response the T-helper-2 (Th) response is activated leading to release of interleukin (IL)-4, IL-5, and IL-13 and the production of allergen-specific IgE which leads to inflammation. Studies have shown that probiotics help prevent allergic diseases by regulating the Th1/Th2 balance by modulating the immune system back to a Th1 response and by preventing inflammation by reducing TNF-a induced NF-?B activation, the major pathway causing an inflammatory response [83]. This is supported by a study demonstrating a reduced eczema severity as well as serum cytokines IL-5, IL-6, interferon (IFN)-?, and total serum IgE levels in children between 1-13 years with a history of atopic dermatitis (eczema) when fed with a probiotic mixture of B. bifidum, L. acidophilus, L. casei, and L. salivarius [85]. In another study with 1-3 years old children, a mixture of probiotics L. acidophilus DDS-1, B. lactis UABLA-12, and prebiotic fructo-oligosaccharides (FOS) helped to significantly reduce eczema severity as compared to placebo group [86]. Moreover, probiotics have also shown to reduce eczema severity in adults fed with L. salivarius LS01 (DSM 22775) for 16 weeks [87].

In context to food allergy there have been studies showing inconsistent results conducted on infants and children fed with Lactobacillus and Bifidobacterium strains when suffering from allergies of cow’s milk, egg or peanut [83]. Similarly, very few studies have been conducted on patients suffering from asthma and showing positive results. In a study, adults given B. breve M-16V and galacto or fructo-oligosaccharides showed reduction in Th-2 cytokine levels but no reduction in bronchial inflammation or improvement in lung function [88]. However in a study on school children suffering from asthma and allergic rhinitis fed with L. gasseri A5 showed reduced cytokine levels and clinical symptoms [89]. Thus there are promising studies showing the benefits of probiotics in the prevention of eczema. However there has been conflicting data and few studies showing the benefits of probiotics in the treatment of food allergy or asthma and allergic rhinitis and hence further research is required to prove its benefits.

Probiotics as a vaccine adjuvant

A large portion of the population in developing countries do not receive vaccines because of limited access. This causes millions of deaths annually from vaccine-preventable diseases, especially among children below 5 years of age infected with pneumococcal bacteria and rotavirus [90]. Probiotics are emerging as a safe, easy to deliver, cost effective and efficient strategy in stimulating both mucosally and parenterally delivered vaccine immune responses. They might act by increasing phagocytic cell activity and production of disease specific antibodies; thus allowing safe administration of vaccines in remote areas and overcoming the requirement for multiple doses [90].

This hypothesis is supported by studies with infants showing that supplementation with L. casei GG increased serum levels of rotavirus specific antibodies IgA and IgM as compared to placebo group with a 8-fold higher rotavirus-specific IgM antibody secreting cell (ASC) response [91]. In another study on infants supplemented with a mix of Bifidobacterium longum BL999 and Lactobacillus rhamnosus LPR, higher serum levels of anti-HBsAg IgG concentrations were seen as compared to the placebo group following Hepatitis B vaccines [92]. Furthermore, adults immunized with live attenuated poliovirus vaccine and fed with L. rhamnosus GG (LGG) or L. paracasei CRL431 orally for five weeks showed higher levels of serum antibodies against poliovirus serotypes 1 and 2 (LGG) and serotype 3 (CRL431) [93]. In another study, adults given influenza vaccine and fed with L. fermentum CECT5716 showed higher levels of virus neutralizing antibodies and T-helper type 1 response [94]. Thus probiotics seem promising in alleviating vaccine preventable diseases in developing countries, however, still large randomized placebo controlled human trials are required to guarantee their benefits.

Consumption of probiotic food products is highly recommended in developing countries because of the proclaimed health benefits which include alleviation of acute diarrheal diseases, increase in natural resistance to infectious disease in gastrointestinal tract and HIV/AIDS, improvement in lactose intolerance, reduction in serum cholesterol levels, improved nutrition, allergy treatment and serving as a vaccine adjuvant. In developing countries there is a lack of awareness about health benefits of probiotics and regulations are needed to ensure that quality and safety standards are met. In the absence of regulations, there could be production of unreliable products containing low levels of the beneficial strains that have no benefits. Hence, funding for this area of research in developing countries is very important to prove that probiotics can help to improve the nutritional and health status of people [1]. Also each nation should develop a strategy pertaining to the needs of the people, cost and compliance issues, increased awareness and consumer confidence which will ultimately lead to acceptance of probiotic products in the society. Some of the approaches could include license free inclusion of probiotics in common food vehicles such as yogurt with a minimal increase in cost, radio publicity and increased Government initiative in informing to people about the benefits of probiotics [1]. Finally, compared to normal therapeutic agents or drugs, probiotic strains are comparatively cheaper to produce, store and deliver which would overall be beneficial for developing regions [2].

We would like to thank Giuliana Salazar-Noratto for the critical review of our manuscript. We thank the Margaret Nicholson Schafer Graduate Fellowship in Food Science and Nutrition for the financial support