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Review Article

Recent Advances in Probiotics and Biomedical Applications

Journal of Medical Sciences: Volume 13 (8): 601-614, 2013

Hassan Pyar, Min-Tze Liong and K.K. Peh

Abstract

Probiotics are defined as “microbial food supplements” with favorable effects on the consumers. The selection of probiotic microorganisms depends on a number of aspects including safety, functional and technological characteristics. Increased incidence of microbial resistance to antibiotics has triggered renewed efforts to develop probiotics in the treatment of gastric aliments. This review outlines the uses of probiotics and their novel applications and developments for healthcare. The biomedical applications of probiotics in the prophylaxis and treatment of different disease conditions such as diarrhea, constipation, hypercholesterolaemia, vaginitis, necrotizing enterocolitis, sepsis, colon cancer, bladder cancer, breast cancer and liver cancer are discussed. Furthermore, stimulation immune system, weight gain improvement in premature infants, reduction of incidence of respiratory tract infections and prevention of intestinal infections are also highlighted and current challenges are described.

How to cite this article:

Hassan Pyar, Min-Tze Liong and K.K. Peh, 2013. Recent Advances in Probiotics and Biomedical Applications. Journal of Medical Sciences, 13: 601-614.

DOI: 10.3923/jms.2013.601.614

URL: https://scialert.net/abstract/?doi=jms.2013.601.614

INTRODUCTION

In addition to restoring the microbial balance of the Gastrointestinal Tract (GIT), products containing probiotic organisms , are also claimed to propose to have several dietary and therapeutic or functional benefits (Berg, 1996). Preventive and therapeutic effects of these agents have been observed in the juvenile diarrhea, travelers’ diarrhea, antibiotic induced diarrhea, lactose intolerance, colon cancer, constipation, hypercholesterolemia, lactose intolerance, virginities and intestinal infections (Frank and Norman, 2008). These effects will be discussed in more detail in the ensuing sections.

Definition of probiotics: The word probiotic is originally a Greek terminology which means “for life” however Lilly and Stillwell (1965) coined the term “probiotics” to differentiate it with the term antibiotics and they described it as a metabolite produced by one organism to supports the growth of other organism. Later, the probiotic was broadly defined as a microorganism and the metabolites which help in equilibrium of intestinal flora (Parker, 1974). Further attempt was made by Fuller (1989) to give more developed definition of probiotics as “a standard microbial supplement which acts synergistically with the host animal by improving its intestinal microbial balance.” This revised definition signifies the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host. Havenaar and Huis (1992) improved further the meaning of probiotics with relationship of host and habitat of the microflora as follows: “A single or a combination of microbial culture which can be used by human beings for the beneficial effects of the indigenous gut flora.” According Naidu et al. (1999) when probiotics are taken in certain amount can provide health benefits beyond their normal nutritional role. The World Health Organization (FAO/WHO, 2001) defined probiotics as living micro-organisms which when administered in sufficient quantity provide beneficial effects in the host (Pineiro and Stanton, 2007).

Microflora of human gastrointestinal tract: The understanding of the function and potential contribution of probiotics towards health and well-being of the human host requires a reasonable knowledge of the human gastro-intestinal tract as ecosystem (Tannock, 1994). Although, the microorganisms, which are commonly known as intestinal micro-flora or micorbiota, are distributed throughout the intestine, the majority of microbes and metabolic activity is formed in the large intestine (Simon and Gorbach, 1983; Berg, 1996; Salminen et al., 1998; Guarner and Malagelada, 2003). The establishment of microflora in the intestine begins shortly after birth and it composition is dependent on number of factors including contact with the maternal intestinal microbiota and surroundings and possibly by genetic makeup of the individual (Salminen et al., 1998). Different parts of the GIT are populated with different types and concentrations of the microorganisms with the highest one in colon having concentration in range of 1011-1012 CFU g-1 (Fig. 1) (Ouwehand and Vesterlund, 2003). Some of the strains with health-promoting beneficial properties exhibit also powerful anti-inflammatory properties (Isolauri et al., 2002).

Types of probiotic: The large prominent and invariably increasing group of microorganisms under the term probiotics has been used in animals and humans. Table 1 lists some of the known probiotics available (Mombelli and Gismondo, 2000; Holzapfel and Schillinger, 2002; Jeon et al., 2012; Kumar et al., 2012; Maldonado et al., 2012; Thomas et al., 2012). Lactobacilli and Bifidobacteria are the two most important types of probiotic implied in the products considered for human use. In addition, yeasts such as Saccharomyces, have also been used (Holzapfel et al., 1998).

Generally the term probiotic does not means anything unless it is having the right strain(s), in the right amount (potency), in the right condition (viable), in the right formulation and most importantly they must be having “Generally Recognized As Safe (GRAS)” status by the Federal Food and Drug Administration. The safety concerns related with these agents are still significant and are under continuous investigation and revision (Blanquet et al., 2005; Leverrier et al., 2005).

BIOMEDICAL APPLICATIONS OF PROBIOTICS

Prevention of diarrhea: About 4 billion diarrhoeal cases per year were reported worldwide, out of which 4% accounts for deaths and 5% for severe disabilities (Sazawal et al., 2006). Gastroenteritis and acute diarrhoeal episodes can be related to viral, bacterial, or parasitic pathogens (Marteau et al., 2001). Many studies have evaluated the use of probiotics in the prevention and treatment of diarrhoeal diseases, particularly in children in the developing world (Van Neil et al., 2002). Antibiotics such as clindamycin, ampicillin and lincomycin upon oral administration usually eradicate the susceptible micro-flora including Lactobacilli, Bifidobacteria, bacteroides and anaerobic cocci (Marchand and Vandenplas, 2000), while the putrefactive bacteria such as Clostridia, Eubacteria and Coliforms are normally not eliminated, resulting in their proliferation that may cause diarrhea and flatulence (Rafii et al., 2008).

Fig. 1: The numerically dominant microbial genera in the adult human gastrointestinal tract (Ouwehand and Vesterlund, 2003)

Table 1: Common probiotics for human use (Mombelli and Gismondo, 2000; Holzapfel and Schillinger, 2002; Maldonado et al., 2012; Thomas et al., 2012; Jeon et al., 2012; Kumar et al., 2012)

Several reports and clinical trials have demonstrated the effectiveness of probiotic cultures for controlling diarrhea and decreasing the symptoms or duration of diarrhoeal illnesses (Shornikova et al., 1997; Vanderhoof, 2000) among these the Lactobacillus strains is the most extensively studied (Allen et al., 2003). In a study conducted by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the patients were given either probiotics or placebo along with standard oral rehydration solution. The patients receiving probiotics showed promising results in-terms of shorter persistence and decreased severity of diarrhea and shorter period of stay in hospital (Guandalini et al., 2000). On the other hand, Shornikova et al. (1997) found that the duration of watery diarrhea was decreased in the group treated with probiotics strains compared with those treated with placebo. Numerous studies have shown improvement in various diarrheal disorders and bacterial infections were treated with probiotics (Benchimol and Mack, 2004; Schrezenmeir et al., 2004). One of the justifications for use of probiotics in the treatment of acute diarrhea is that they act against intestinal pathogens and possible mechanism for their antimicrobial activity is the increased production of intestinal mucin, inhibition of adhesion of pathogens, modification of toxin and non toxin receptors, stimulation of immune responses to pathogens and they prevent the attachment of enteropathogen (Szajewska and Mrukowicz, 2001; Hajela et al., 2010). Thus, these reports convincingly demonstrate usefulness of probiotics to treat diarrahea.

Prevention of intestinal infections: As far back as the early 1900s, a Russian scientist suggested that disease and the aging process came as a result of “auto intoxication” due to pathogenic bacteria producing phenols, indoles and ammonia in the gut. Thus, supplementing the gut flora with fermented foods that contained probiotics bacteria seemed to have many health benefits. Traditionally, probiotics have been used to treat the intestinal infections. The intestinal environment is host to billions of good bacteria and these play a critical role in the body’s health (Raftaniamiri et al., 2010). Studies have shown the therapeutic and preventive effects of probiotics in number of intestinal infections and these agents have been scientifically proved to treat infection, the possible underlying mechanism may be the production of antibodies against these infections (Walker and Duffy, 1998; Solis et al., 2002). Moreover, probiotics also act against the bacteria responsible for stomach ulcers (Park et al., 2007). Several probiotic strains have been observed in vitro for their ability to avoid intestinal colonization of pathogens and found that probiotics have an ability to inhibit colonization by a large variety of pathogens using a model with intestinal Caco-2 cell line (Langerholc et al., 2011). In another study, intestinal glycol-proteins extracted from faeces were used to study pathogenic E. coli and Salmonella strains and the effect of probiotics on adhesion (Tuomola et al., 2006). Besides producing antimicrobial agents probiotic bacteria also interfere with adherence of several human pathogens to intestinal cells (Forestier et al., 2001). Above all, probiotic bacteria produce many organic helpful organic acids such as, lactic, acetic and citric acids, that interferes with growth of GIT pathogens (Mirhosaini et al., 2006; Nagalakshmi et al., 2013).

Prevention of constipation: Constipation is a very common condition in which one has a hard time passing wastes out of the body. The most common symptoms of chronic constipation are abdominal bloating and bad breath. The prolonged chronic constipation may increase the risk of getting colon cancer. Irritable Bowel Syndrome (IBS) results in abdominal problems, bloating, diarrhea, constipation and flatulence most of these are due to motor as well as sensory dysfunction of the gastrointestinal tract (McFarland and Dublin, 2008). There has been an increased interest in using probiotics to treat a variety of intestinal disorders including diarrhea and constipation (Giannini et al., 2006; Kajander et al., 2007). De-Vrese and Marteau (2007) reported that constipation due to colonic dysfunctions was reduced using products containing probiotic bacteria and their antibacterial properties and thus reduced the need of laxatives in elderly patient hospitalized for constipation process (Lamiki et al., 2010). Probiotics almost certainly have at least two modes of action in improving constipation. First, dysbiosis in the gut flora plays a role in constipation and might be improved by probiotics (Szajewska and Mrukowicz, 2001); second, probiotics are capable of lowering the pH of the colon through the production of lactic, acetic and other short chain fatty acids which in turn enhances peristalsis and helps in constipation (Picard et al., 2005; Elias et al., 2011). Vazquez (2010) evaluated the efficiency of different laxatives and concluded that excitant laxatives may be more effective than bulk laxatives in ameliorating constipation during pregnancy by enhancing bowel movements and relenting the stools. However, their use is circumscribed due to side-effects such as abdominal pain and diarrhea. Hence, alternatives that are safe for pregnant women and the fetus are needed. These alternatives must be in harmony with the guidelines for treatment of constipation during pregnancy (Tytgat et al., 2003). Probiotics might also be effective in the intervention of constipated pregnant women (Gill and Guarner, 2004). Several randomized controlled trials studies to investigate the safety of probiotics shown that probiotics are safe for mother and fetus during pregnancy and did not report an increase in undesirable actions related to probiotics (Boyle et al., 2008; Kukkonen et al., 2008; Luoto et al., 2010; De Milliano et al., 2012).

Prevention of hypercholesterolaemia: Recently, the main focus of national dietary recommendations is an increased attention towards lowering the fat intake through diatery supplements (Hu et al., 2001). One of the risk factors for coronary heart disease is the high serum cholesterol levels associated with high consumption of dietary fats (Jousilahti et al., 1998). Therefore, reduction in fat intake has been considered the main strategy to combat elevated serum cholesterol levels (Hu et al., 2001). Recent therapies for decreasing the blood cholesterol levels include dietary management, regular exercise, behavioral modification and drug therapy. Several studies have suggested a reasonable cholesterol lowering action of dairy products fermented with assured strains of probiotic bacteria (Noh and Gilliland, 1993; Bastani et al., 2012). L. acidophilus has generally been known as to deconjugate bile acids which lower and inhibit increases in serum cholesterol although serum cholesterol reduction is strain specific (Brown et al., 1999; Kumar et al., 2012). Probiotic bacteria reduce absorption of cholesterol in the intestine by binding to it and consequently incorporating it into the cell membrane (Noh and Gilliland, 1993). All of the above-mentioned activities collectively aid the cholesterol-lowering actions of probiotics.

In general, most of the studies have led to a conclusion that dietary intake of fermented products containing Lactobacillus strains lowers serum cholesterol. A number of mechanisms have been suggested for the cholesterol-lowering action of probiotic bacteria (Brashears et al., 1998; Ahn et al., 2003). The most accepted mechanism includes assimilation of cholesterol by biological effect of the metabolites of short-chain fatty acid fermentation, catabolism of cholesterol by the bacteria and deconjugation of bile acid by hepatic enzymes.

Lactose intolerance: Studies shown that lactose-intolerant individuals encounter less problems if the milk in the diet is replaced with fermented dairy products (Salminen, 2001). Different products may have varying lactose contents and numbers of bacterial cells which, when released to the duodenum, vary in their lactase activity (Salminen et al., 1998; Schrezenmeir and de Vrese, 2001). Consumption of products containing probiotic cultures such as L. acidophilus is reported to be beneficial to human lactose maldigestors on a long-term basis (Hekmat and McMahon, 1992; Kaplan and Hutkins, 2000). It is shown that, in the duodenum and terminal ileum β-galactosidase enzyme produced by probiotics helps in hydrolysis of lactose (Salminen et al., 2003). In addition, the slower gastric emptying and intestinal transit of probiotics products also contributes in hydrolysis of lactose (Saarela et al., 2000).

In conclusion, there is good scientific evidence of probiotic strains and concentrations being useful for alleviating symptoms of lactose intolerance and may render the hydrogen breath test negative when consumed at the same time as a lactose-containing dairy product. Further, some probiotics colonize the intestine; hence probiotics may provide a longer-term solution for some patients than the typical lactase supplements which only act when taken concurrently with the lactose-containing dairy food (Lin et al., 1998). Streptococcus thermophilus, a group of Streptococcus salivarius microorganisms, has a strong ability to ferment lactose; therefore it has been widely used in probiotics. The production of lactase by probiotics is thought to improve the digestion of lactose in lactose intolerant patients (Sanders, 2000).

Prevention and treatments of vaginitis: Bacterial vaginosis is the most common urogenital disease in women, affecting about 19-24% of them in reproductive ages (Parent et al., 1996). Candida vaginitis, bacterial vaginosis and other gynaecological infections are a result poor colonization of vaginal flora imbalance (Cribby et al., 2008). Normal vaginal flora balance can be restored by administration of probiotics (Marcone et al., 2008). Effect of ingestion of L. acidophilus yoghurts on vulvo-vaginal candidal infections in women with recurrent candidal vaginitis has been tested. The most profitable dose and treatment duration must be taken into consideration as well. The desquamated vaginal epithelial cells release glycogen which supplies probiotics bacteria with nutrients. These probiotics degrade glycogen and create an acidic environment which restricts the growth of pathogenic microorganisms (Boskey et al., 2001). Results indicate positive vaginal influence of active cultures of L. acidophilus consumed live at levels of 108 CFU mL-1 and at a weight of eight ounces daily (Reid et al., 1990; Shalev et al., 1996). Application of probiotics via the urogenital tract has been investigated by Bastani et al. (2012). They confirmed the potential efficacy of Lactobacilli as a non chemotherapeutic means to restore and maintain a normal urogenital flora. They also show that probiotic bacteria especially L. acidophilus can most appropriately normalize vaginal flora and help cure existing and prevent recurrence of vaginitis infection. However, since vaginitis is a common disorder, to prevent it the vaginal flora needs to be normal and devoid of pathogens by the help of beneficial bacteria. This suggests that women should consume probiotic foods because it will not only protect them against vaginitis but will also reward them with other health benefits of probiotics.

Prevention of sepsis: Probiotics are commonly used as the preventive and therapeutic modalities for antibiotic associated and acute infantile diarrhea and are also shown to be effective for treatment of Helicobacter pylori infection (Bengmark, 1996). The use of probiotics is getting in popularity since the incidence of sepsis increases. It is approximated that the rate of sepsis will increase by 1.5% each decade which is the tenth most frequent reason for death in the United States (Angus and Wax, 2001). Preterm delivery also is on the rise and is associated with a large percentage of the deaths associated with NEC in the United States (Angus and Wax, 2001). Consequently, preterm newborns represent a target population for probiotic research. Unlike breastfed term newborns, preterm newborns in intensive care units suffer from a very abnormal pattern of bowel colonization (Blakey et al., 1982). Intensive use of antibiotics, infection control procedures, reduced exposure to maternal microflora as well as sterile feedings all contribute to the progression of irregular colonization (Millar et al., 2003; Saavedra, 2007). The lack of microbial diversity in the bowels of preterm infants may predispose them to certain strains of sepsis such as those caused by Staphylococci, Enterobacteriaceae and Enterococci. Probiotics can encourage bowel colonization with beneficial flora, thereby potentially protecting infants against life-threatening disease (Saavedra, 2007).

Immune system stimulation: The main function of gut flora is the development and homoeostasis of the immune system (Guarner and Malagelada, 2003). One of the numerous beneficial effects attributed to probiotic Lactic Acid Bacteria (LAB) was the stimulation of the immune system (Rescigno, 2009). The main mechanisms in promotion of bacterial translocation are overgrowth of bacteria in the small intestine; improved permeability of the intestinal mucosal barrier and deficiencies in host immune defenses (Berg, 1999). Colonization of the gastrointestinal tract by probiotics such as lactobacilli and bifidobacteria strains results in immunomodulation via the gut associated lymphoid tissue (Delcenserie et al., 2008). In the immune system, macrophages play significant roles in the preservation of health by their ability to eliminate defective cells, invading microorganisms and poisonous substances. The immune responses of the host are orchestrated by macrophages through the production of cytokines and chemokines. Lactobacilli stimulate macrophage functions and this activity varies among Lactobacillus strains (Matsuguchi et al., 2003). A study by Sanders (2000) reported that administration of mixed culture of L. acidophilus and L. casei in mice resulted in greater stimulated macrophage activity, prevented colonization of the liver and spleen by pathogenic microorganisms in mice. Significantly higher levels of circulating antibodies and elicited the strongest stimulation of the host immune system comparing to control mice. They further reported that consumption of live active probiotic cultured in higher interferon production in lymphocytes enhances the immunogenicity of mucosal and systemic vaccines (Gill and Guarner, 2004). In a randomized double blind study, subjects fed yoghurt containing L. rhamnosus and L. paracasei manifested significantly higher virus neutralising antibody responses (mainly IgA) to a live attenuated polioviruses vaccine, compared with subjects given placebo (Youn et al., 2012). Licciardi and Tang (2011) confirm that consuming supplementation with probiotics L. acidophilus and B. infantis has also been shown to improve immune responses to Salmonella typhi and polioviruses immunization.

Weight gain improvement in premature infants: In infants the weight gain benefits of probiotics has been studied by many investigators investigated (Berg, 1998). One randomized and controlled trial investigating the effects of probiotics on the weight of infants showed that infants feed with supplements with B. breve had higher rates of fecal bifidobacterial colonization, decreased gastric aspirate volume, improved feeding tolerance and enhanced weight gain (Kitajima et al., 1997). In another double-blind, randomized study on 120 healthy infants receiving L. rhamnosus GG supplemented formula or regular formula up to two years of age and showed that the supplemented infants had significantly greater changes in length and weight and grew significantly better by the end of the study than the control group (p<0.01) (Vendt et al., 2006).

Reduction of incidence of respiratory tract infections: Respiratory Tract Infections (RTIs) include the common cold, tonsillitis, acute rhino sinusitis, acute pharyngitis, acute croup (laryngotracheobronchitis), inflammation of the trachea, acute supraglottitis (epiglottitis), laryngitis and acute otitis media with symptoms including fever, cough, pain and headaches are a major cause of morbidity, especially in children and adults (Duijvestijn et al., 2009; Kassel et al., 2010). They are caused by many viruses and bacteria (Liberati et al., 2009). Acute RTIs are the most common reason for people to request medical care all around the world (Cherry and Nieves, 2012). Antibiotics are prescribed if the illness becomes chronic and complications develop (Hao et al., 2011). Probiotics can confer a health benefit to the patient when administered in adequate amounts on the severity and duration of symptoms of Respiratory Tract Infections (RTIs) by several research groups (Vouloumanou et al., 2009; Guillemard et al., 2010; Lenoir-Wijnkoop et al., 2007) inspected probiotic efficacy consumption on airway and gastrointestinal infections employed by L. rhamnosus GG, while L. fermentum VRI 003 and found that highly significant reduction in the number of days with respiratory (Cox et al., 2010). Hao et al. (2011) showed a benefit in using probiotics to prevent acute RTIs and showed that live probiotics could reduce the prescription of antibiotics. Vouloumanou et al. (2009) evaluated the clinical evidence regarding probiotic use for the prevention of RTI. The administration of probiotics may have a beneficial effect on the severity and duration of symptoms but does not appear to reduce the incidence of RTI (Deshpande et al., 2011).

Prevention of necrotizing enterocolitis: Necrotizing Enterocolitis (NEC) is the most common abdominal emergency in preterm infants in intensive care units and is potentially fatal. The abnormal pattern of gastrointestinal colonization of preterm infants may be a contributing factor to the pathogenesis of NEC (Millar et al., 2003). Changes in bacterial metabolic activities precede NEC onset with the fermentation of carbohydrates to produce intramural gas (Cheu et al., 1989). The recommended benefits of probiotics are improved mucosal fidelity, averting of bacterial translocation and much better tolerance to enteral nutrition which can decrease the need for intravenous nutrition and control of the immune response. All of these lead to reduced incidences of infection and intestinal disease. Cheu et al. (1989) found that the useful bifidobacteria commonly found in the term newborn digestive tract were undetectable in the intestinal flora during the first two weeks after birth in preterm infants, even though they were being breastfed (Lin et al., 2008). The bacteria did not predominate until after the third postnatal week. Blakey et al. (1982) documented similar findings on the other hand Gewolb et al. (1999) observed bifidobacterial and lactobacilli in stools of fewer than 5% of extremely low-birth weight infants in the first week after birth. Caplan et al. (1999) in a neonatal rat model the bifidobacteria supplementation resulted in intestinal colonization together with reduction in NEC-like scars. In another multicenter double-blind Italian study, preterm infants were randomized to receive a placebo or L. rhamnosus GG (Dani et al., 2002). Researchers identified a decrease in NEC, despite the fact that the difference was not statistically significant. A research group from South America showed that a threefold decline in NEC and a fourfold decrease were observed in NEC-related mortality after the prophylactic administration of bifidobacteria supplemented feeding (Hoyos, 1999). In a prospective, randomized, blinded survey, 367 breastfed preterm infants were randomized to receive either L. acidophilus and B. infantis supplements twice daily or feeding without supplements (Lin et al., 2005). A threefold decrease in NEC and NEC associated mortality following prophylactic probiotic administration was observed.

Anti-tumor effects: The immune system is an important line of defense for tumor formation of malignancies that express unique antigens (Mager, 2006). It has been estimated by the American Institute for Cancer Research and the World Cancer Research Fund that 30-40% of all cancers can be prevented by appropriate diets, regular physical activity and the maintenance of appropriate body weight (Glade, 1999). Beneficial bacteria help strengthen the immune system right in the gut where much of the interaction between the outside world and the body occurs. They can also help prevent food allergies and cancer at various stages of development. Probiotics can improve mineral absorption, maximizing food utilization (Donaldson, 2004). There is some evidence that dietary adjuncts may aid in preventing some forms of tumors. Goldin (1998) reported a decrease in the number of rats which developed chemically-induced intestinal cancer for those fed diets containing L. acidophilus. On the other hand, Asano et al. (1986) found that consumption of milk fermented with L. acidophilus inhibited the formation of Ehrlich ascites tumor cells in lab mice by greater than 30%. Takeda and Okumura (2007) asserted that the continuous intake of the fermented milk containing Lactobacillus strains is effective to augment NK-cell activity; this is of particularly importance in individuals who have low levels of NK-cell activity. A strain from L. casei has been shown to have potent antitumor effects in rodents (Hori et al., 2001). Probiotics are cheap and nontoxic compared with many chemotherapeutic agents (Borchert et al., 2008). Fotiadis et al. (2008) reported that L. casei appeared to have antitumor and antimetastasis effect in mice.

Prevention of colon cancer: The colon is one of the most common sites for tumor formation (Aso et al., 1995). It is in the area of prevention of one of the most deadly cancers of the colon that probiotics offer stellar benefits. Probiotics acidify the colon with the production of short chain fatty acids. However, low incidence of colon cancer is associated with low colon pH. Further, the level of procarcinogenic enzymes such as beta-glucuronidase, nitroreductase and azoreductase are reduced by probiotic bacteria (Goldin and Gorbach, 1984). The ability of intestinal bacteria to biotransform primary bile salts into secondary by the biochemical effects of probiotics resulting in the inhibition of tumor formation (Zimmer and Gibson, 1998; Kechagia et al., 2013). In another study, the correlation between diet and colon cancer was explained by the alteration of fecal bacterial enzyme activity caused by the western-style diet which is low in fiber but high in meat and saturated fat (Cummings et al., 1978; Carrera-Bastos et al., 2011). Supplementary use of probiotics also has merit as anticancer dietary measures (Donaldson, 2004). Fermented products made by using lactic acid bacteria culture such as L. acidophilus and L. casei cultures in fact have anticarcinogenic effects. The anticarcinogenic effect of L. acidophilus is reported as its capability to reduce-glucuronidase, nitroreductase and azoreductase (faecal enzymes) known to convert procarcinogens into carcinogens (Kailasapathy and Rybka, 1997). However, it is suggested that the destruction of carcinogens such as nitrosamines. Matsuzaki and Chin (2000) stimulate the immune system to more effectively fight cancer cells as well as to trigger apoptosis and reduction in the level of faecal bacterial enzymes (Moore and Moore, 1995). A large study by Matsuguchi et al. (2003) observed 400 patients with colorectal tumours for more than 4 years. The most positive results from the study were for the group taking the probiotic. While incidence of new tumors in this group was no less compared with the control group, the rate of tumor development was significantly slower. This provides strong evidence in favour of colon cancer reduction mechanisms (Loose and Van De Wiele, 2009).

Risk reduction of bladder cancer: The escalating costs of antibiotic therapy and the manifestation of multi-resistant bacteria and more important for patients and clinicians, unacceptable therapeutic options in frequent urinary tract infection call for alternative and advanced medical solutions. In early the 1980s, several experimental studies have pointed out the potential mechanisms through which probiotics can prevent bladder cancer, including inhibition of carcinogens and their cytotoxic effects together with local and systemic modulation of the immune response (Asano et al., 1986). Recent studies have shown preventive effects of probiotics against recurrence after transurethral resection of superficial bladder cancer (Aso and Akazan, 1992; Aso et al., 1995; Naito, 2009). The effect on the immune system of healthy people has also been recommended by regular intake of probiotics which has been shown to reduce bladder cancer. They are also potentially protective for cancer progression and development (Ohashi et al., 2002). Probiotics show promise in becoming an alternative or complementary treatment option for many diseases with it is impact could have on bladder cancer therapy (Hoesl and Altwein, 2005).

Prevent the development breast cancer: Breast cancer is one of the most serious diseases throughout the industrialized world and in many developing countries. Lactobacillus strains inhibit beta-glucuronidase, a fecal bacterial enzyme that prevents the body from detoxifying more potent forms of estrogen (for instance estradiol) into nontoxic forms (e.g., estriol). Hence, probiotics may possibly play a major role in normalizing the digestive tract flora that would help to defuse noxious estrogen (Chen et al., 2002).

Prevent the development liver cancer: Hepatic cancer is the sixth most commonly diagnosed cancer worlwide. The liver, a major organ of the body, is involved in many processes of the body. These include the manufacture of various essential proteins, processing and storing nutrients and the destruction of toxins and poisons. Probiotics are effective and helpful to patients for a number of conditions. Probiotics have a promising future in the prevention of several cancers and researchers are turning their attention to the use of probiotics to treat liver cancer (Ferguson and Philpott, 2007).

Liver disease is increasing side by side with the increase in obesity and Type 2 diabetes. The manipulation of the gut microflora may be an approach to control the development of NAFLD (Kirpich and McClain, 2012). A daily supplement of probiotics may increase the strength of the difficulty function by changing gut flora for the better (Sleator and Hill, 2008). It may also help in prevention of low-grade inflammation, hence having a beneficial effect in halting several types of liver disease such as NAFLD and hepatitis (De LeBlanc et al., 2007). Aflatoxins are liver carcinogens found in a number of foodstuffs, particularly low quality peanut butter (Sheth and Garcia-Tsao, 2008). A study that inspected the capacity of Lactobacilli to bind to and kill food borne carcinogens, a strain of probiotic showed potential in the detoxification of Aflatoxin B1, Aflatoxin B2, Aflatoxin G1 and carcinogens to the liver. These acted by binding to the toxins and thus prevented the toxins from mutating the liver DNA which reduce risk factors for liver cancer onset (El-Nezami et al., 1998; Sheth and Garcia-Tsao, 2008). Probiotics bacteria are able to bind >107 aflatoxin B1 (AFB1) molecules and binding appears to arise on the bacterial surface principally by hydrophobic interactions between the AFB1 molecules and the carbohydrate and protein mechanism of the bacterial cell wall (Haskard et al., 2000). Loguercio et al. (2002) used the term “gut liver axis” for probiotics because of hepatoprotective effects of these agents. Intestinal absorption of aflatoxin B1 can be blocked by probiotics consumption which results in reducing urinary excretion of aflatoxin B1-N7-guanine (AFB-N7-guanine), a marker for a biologically effective dose of Aflatoxin exposure. This may therefore offer a powerful nutritional approach to decrease the danger of liver cancer (El-Nezami et al., 2006).

CONCLUSION

There is an increased interest in the use of probiotics in the treatment of human diseases. Many microbes have been investigated and applied therapeutically. A number of diseased conditions have been observed to be due to in vivo microbial imbalance and the consequent conditions remedied by the application of appropriate probiotics. Probiotics can protect infants against life-threatening disease by improvement of bowel colonization with beneficial flora. These agents are also known to stimulate the immune system. Therefore, it is hoped that the present review has successfully demonstrated perspectives for further study of probiotics and thus it will stimulate the interest of researchers to explore this research field.

ACKNOWLEDGMENT

The present study was financially supported by the Universiti Sains Malaysia (USM) Grant Number: (1001/PFARMASI/843084) and a USM Graduate Assistance Scheme.

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