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Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2011, Article ID 981214, 12 pages doi:10.

1155/2011/981214

Review Article The Gut Microbiota and Human Health with an Emphasis on the Use of Microencapsulated Bacterial Cells
Satya Prakash, Catherine Tomaro-Duchesneau, Shyamali Saha, and Arielle Cantor
Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC, Canada H3A 2B4 Correspondence should be addressed to Satya Prakash, satya.prakash@mcgill.ca Received 19 November 2010; Revised 16 February 2011; Accepted 11 April 2011 Academic Editor: Eric C. Martens Copyright © 2011 Satya Prakash et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The gut microbiota plays a crucial role in maintaining health. Alterations of the gut bacterial population have been associated with a number of diseases. Past and recent studies suggest that one can positively modify the contents of the gut microbiota by introducing prebiotics, probiotics, synbiotics, and other therapeutics. This paper focuses on probiotic modulation of the gut microbiota by their delivery to the lower gastrointestinal tract (GIT). There are numerous obstacles to overcome before microorganisms can be utilized as therapeutics. One important limitation is the delivery of viable cells to the lower GIT without a significant loss of cell viability and metabolic features through the harsh conditions of the upper GIT. Microencapsulation has been shown to overcome this, with various types of microcapsules available for resolving this limitation. This paper discusses the gut microbiota and its role in disease, with a focus on microencapsulated probiotics and their potentials and limitations.

1. Introduction
The gut microbiota, which resides in the gastrointestinal tract (GIT) and is also termed microflora, plays an important role in human health and disease. The GIT is comprised of the stomach, the duodenum, the jejunum, the ileum, the colon, the rectum, and the anal canal. The lower digestive tract, specifically the colon, is the primary site of importance for bacterial cell colonization; however, upper digestive tract microorganisms are also of importance. The bacterial population of the gut has been studied in diseases such as colon cancer, inflammatory bowel diseases (IBD), hypercholesterolemia, nonalcoholic fatty liver disease (NAFLD) and others. Certain bacterial populations, such as lactic acid bacteria, have been shown to positively influence health. Hence, attempts to modify the microflora, towards those bacteria, for disease treatment and prevention should prove advantageous. For this purpose, prebiotics, probiotics, and synbiotics have been used. The delivery of viable probiotic bacteria is impeded by the harsh conditions of the upper GIT, hence, a vessel for delivering optimum cell viability to the lower GIT is required. Microcapsules can be used as a

vehicle with the capability to protect the viability and activity of orally delivered bacterial cells through the upper GIT. This paper will first give an overview of the gut microbiota and its main characteristics, focusing on its role in colon cancer, IBD, and hypercholesterolemia. Modulation of the gut microbiota to promote health will then be described through the use of probiotics, prebiotics, and synbiotics, with probiotics as a main focus. Microencapsulation and types of microcapsules will be described along with their success in the treatment and prevention of diseases. Finally, the paper will conclude with a discussion on this field’s future.

2. The Gastrointestinal Bacterial System
The gut microbiota contains a broad spectrum of microorganisms, totalling 1013 to 1014 bacterial cells, but has not been completely explored as of yet [1]. The importance of the gut microflora is exemplified by the fact that the number of bacterial cells outnumbers human cells by a factor of ten [2]. The human intestinal habitat contains 300 to 500 different species of bacteria, varying significantly in content

bile. 5]. and pancreatic secretions which are toxic to most microorganisms. the constant interaction between the host and its microbes usually remains beneficial to the health of the host [4]. The main genera of facultative anaerobic bacteria are Escherichia. Enterobacter. and Ruminococcus [4. Most gut bacteria reside in the lower part of the digestive tract. made up of the stomach and the duodenum. depending on a number of genetic and environmental factors. with the predominant microorganisms present being Lactobacilli and Streptococci [6. bile salts.2 Journal of Biomedicine and Biotechnology Aerobic organisms (upper GIT) Anatomical GIT region pH of GIT region Main contents of the region Number of bacterial cells/gram of GIT region contents Prominent bacterial populations Stomach 1-2 Pepsin. 14. in the large intestine. which can withstand these harsh conditions. Lower in the digestive tract are found the jejunum and the ileum where there is a gradual increase in the bacterial numbers from 104 to approximately 107 cells per gram of contents by the time the distal ileum is reached [7]. One important organism found in the stomach. can be explained by the presence of high levels of acid. Klebsiella. The dominant anaerobic genera are Bacteroides. and bacterial cell counts) and the localization of the various gut bacterial populations. Even though some bacterial species of the gut are potential pathogens. mucus < 103 Lactobacilli. Eubacterium. Bifidobacterium. and Proteus [4. . Clostridium. 11–13]. although some are of great importance in human disease. bile. due to its abundant bacterial population. with the functions broadly qualified as metabolic. since the upper tract consists of high levels of acid. 7]. Enterococcus Faecalis Large intestine 5-7 Anaerobic organisms (lower GIT) Ascending colon Transverse colon Descending colon Bicarbonate. trophic. is Helicobacter pylori. Enterococcus. bacterial populations. between individuals [3]. as shown in Figure 1 [3]. It has been demonstrated that the gut bacterial population plays an important role in their host’s metabolism and energy consumption. as aforementioned [7. There is also a phasic propulsive motor activity in the upper GIT which impedes any stable bacterial colonization [10]. The main functions of the microflora were mostly elucidated by investigations with animals bred under germ-free conditions. harbours very low numbers of microorganisms. Once in the large intestine. 11]. Bacteria are classified into genera and species based on their individual phenotypic and genotypic characteristics. bicarbonate. with less than 1000 bacterial cells per gram of contents. Bacteroides. streptococci Small intestine 6-7 Duodenum Jejunum Ileum Pancreatic enzymes. the tract is heavily populated by anaerobes with up to 1012 cells per gram of luminal contents [10]. a microorganism responsible for ulcers and stomach cancer [9]. termed microbiota. mucus 104−7 Lactobacilli. pH. Bifidobacterium bifidum Figure 1: The GIT characteristics (oxygen distribution. Peptostreptococcus. amylase (from salivary glands). The relatively low number of microorganisms found in the upper digestive tract. 8]. and protective [3. The upper portion of the GIT. 15]. Lactobacillus. This paper focuses on the lower part of the digestive tract. The proportion and numbers of these bacteria can vary. Peptococcus. and pancreatic secretions. Escherichia coli. mucus 1010−12 Lactic acid bacteria. with a number of different genera found actively residing in the human GIT. including disease state and one’s food intake [1. especially in the digestion and absorption of nutrients [1. 11].

Hypercholesterolemia is a disorder whereby an individual demonstrates an elevated serum cholesterol level. specifically. It was proposed that the effect of diet could be mediated by changes in the composition of the colonic microflora such that the intestinal bacteria are responsible for the initiation of colon cancer [3. vegetables. For many decades now this disorder has been recognized as a significant risk factor associated with atherosclerosis and coronary heart disease [45]. the number of Coriobacteriaceae is correlated with higher 3. with the bacterial flora as an important factor and contributor of the inflammation [36. folic acid. there are several environmental factors that have also been implicated in the development of sporadic colon carcinomas [3. suggesting that the resident bacteria are causing the inflammation [39]. the rate-limiting enzyme of cholesterol biosynthesis [46]. 31]. Several mechanisms have been proposed as methods by which the gut microbiota may modulate cholesterol levels within the host [51]. an overpopulation of the Bacteroides genera on the gut epithelium leads to an increased occurrence of transmural inflammatory lesions [3]. Furthermore. grains. such as processed meats. 3. the number of Bifidobacteria found in the gut is positively correlated with higher levels of high-density lipoprotein (HDL) [52–54]. such as diarrhoea. a new paradigm is suggested for the development of a successful treatment. nonetheless showed higher serum-cholesterol values than control rats administered the same diet [50]. Inflammatory Bowel Disease and the Gut Microbiota. participating in microbial-mammalian co-metabolism. 30]. among others [13. IBD. Sufferers of IBD have a higher bacterial attachment to gut epithelial surfaces when compared to that found in healthy individuals [38]. the importance of the gut microbiota in cholesterol metabolism and the pathogenesis of hypercholesterolemia. As early as 1959. Current treatment options to lower serum cholesterol levels involve the use of pharmacological agents such as statins which act by inhibiting HMG-CoA reductase. have been associated with an increased risk of colon cancer development when compared to the risk associated with a high intake of fruits. and biotin by the gut microbiota [22]. were specifically shown to synthesize significant amounts of vitamin B12 [23]. Role of the Gut Microbiota in Colon Cancer. Data shows that bacteria of the Bacteroides and Clostridium genera were associated with an increase in the incidence and growth rate of colonic tumors in tumor-induced animals. Recent developments have demonstrated that the composition of the microbiota and diet is directly correlated with cholesterol levels in vivo.2. Bearing the potential significant consequences of hypercholesterolemia in mind. The Gut Microbiota and Its Role in Human Health and Disease The gut microbiota has gained importance in disease aetiology and pathology.. A number of diseases have been associated with alterations of the gut microbiota. mucosal inflammation in animals with IBD. Although the genetic mechanisms of colorectal cancer are well established. while genera such as Lactobacillus and Bifidobacterium (well-characterized bacteria predominantly used in therapeutic probiotic formulations) appeared to prevent tumorigenesis [32. using rats and mice treated with broad-spectrum antibiotics [39]. coli were found to be more frequent in UC and CD patients when compared with healthy controls [43. the gut microbiota has extensive roles to play in normal human metabolism. 44]. termed dietary fibers and also plays an important role in the biotransformation of conjugated bile acids. prominent in Western countries. 42]. The microbiota is considered a multifunctional organ with metabolic capabilities that humans have not yet fully evolved into their own genomes [16]. 24]. administered a diet without significant amounts of cholesterol. Experiments on a chick animal model demonstrated the synthesis of riboflavin.Journal of Biomedicine and Biotechnology The gut microbiota has a significant impact on host metabolism.1. although only temporarily. but may also include severe liver and skeletal abnormalities [47–49]. The importance of the gut microbiota in vitamin synthesis was demonstrated many years ago with the use of germ-free animals [21]. The link between intestinal mucosal inflammation and the resident bacteria has been further demonstrated. Furthermore. including gastrointestinal problems. vitamin B. nicotinic acid. This effect appears to be species specific as only certain phylogenetic groups of E. The properties of the colonic microflora make it a promising target for the development of a colon cancer therapeutic [34]. E. coli has also been linked to CD. and fish [30. with emerging evidence demonstrating its role in disease [1. in vivo. pantothenic acid. is made up of a group . described in more detail later in this paper [17–20]. hypercholesterolemia and nonalcoholic fatty liver disease. As described. It has the ability to break down indigestible plant polysaccharides. Foods. This treatment mitigates. Some disorders associated with the microflora include colon cancer. Colorectal cancer is the second most common cause of cancer death in men and women [29]. Statins make up a group of compounds that are generally well tolerated but remain expensive and have significant side-effects. 24–28]. with the presence of specific adherent-invasive species found in the resected ileum of patients [41. two resident organisms of the small intestine. Gut Microbial System and Hypercholesterolemia. 37]. vitamin B12 . It is clear that the gut microflora plays an important role in IBD pathology and an efficient therapy is still required.3. and if one can elucidate the exact link between the two one can begin to successfully treat and prevent these disorders through the modulation of the number and/or species of microorganisms present. The two most prominent forms of IBD are Crohn’s Disease (CD) and ulcerative colitis (UC). 13]. Pseudomonas and Klebsiella sp. which contain high levels of dietary fat. 3. 33]. 3 of disorders that are characterized by a chronic and relapsing inflammation of the GIT [35]. thiamine. IBD. In contrast. 3. research was performed to elucidate the role of the gut microbiota in cholesterol homeostasis with researchers demonstrating that germ-free rats. Early research demonstrated that the presence of Escherichia coli is linked to active UC and contributes to the development of inflammation [40].

Another research group demonstrated that Lactobacillus rhamnosus GG. are widely accepted by the general public. On the other hand. Other microorganisms occasionally used as probiotics are yeasts and filamentous fungi [63]. Antibiotics can prove beneficial in short-term use but their prolonged use may result in significant side-effects. Additional studies demonstrate a reduction of colon tumorigenesis markers following the incorporation of Lactobacillus acidophilus in a high-fat control diet in DMH colon cancer rats [98]. confer a health benefit on the host” [62].1. With these facts in mind. It was demonstrated that 93. The FAO and WHO define probiotics as “live microorganisms which. A trial in ulcerative colitis (UC) patients was performed to study the effect of the delivery of an oral probiotic capsule on the remission of the disorder [99]. The probiotic Bifidobacteria were administered following treatment with an UC standard therapy [99]. these are naturally occurring organisms found in foods such as milk and yoghurt and. considered “good. and storage properties of bile acids and by influencing the lipoperoxidation through bile acid signalling properties [19]. A number of other studies related to the effects of probiotics on the prevention and the treatment of IBD. A significant reduction in inflammation was also observed in the treatment group when compared to the control group [99]. 98]. Gut microbial activities influence lipid metabolism. IBD. when administered in adequate amounts. Current research focuses on prebiotics. especially Bifidobacteria. and have already demonstrated beneficial effects for treating immunological. Prebiotic molecules consist of naturally occurring or synthetic sugars used by certain colonic bacteria. in lyophilized form incorporated in a high-fat diet. and respiratory diseases [62]. 97]. with varying success [100]. interaction with the DMH metabolites azoxymethane or methylazoxymethane) leading to a decrease in the potency/availability of the carcinogenic compound [97. important components of the healthy gut microbiota and regarded as safe by the American FDA [63]. and a combination of both. bearing a significant impact on hypercholesterolemia. Journal of Biomedicine and Biotechnology acid bacteria. The Food and Agriculture Organization of the United Nations defines a prebiotic as a “non-viable food component that confers a health benefit on the host. termed synbiotics for modulating the gut microbiota. A study was also performed with hyperlipidemic patients who were administered the probiotic Lactobacillus sporogenes over a three-month period [102]. a 32% reduction in total cholesterol levels accompanied with a 35% reduction in 4. safe. as a carbon source for growth and metabolism [56]. on average.2-dimethylhydrazine(DMH-) induced colon cancer in rats showed a decrease in mortality rate if the test animals were fed Streptococcus thermophilus-fermented skim milk [94]. prausnitizii and its supernatant were both found to have anti-inflammatory effects in vitro using peripheral blood mononuclear and colon adenocarcinoma cells and in vivo in a mouse model of induced colitis [36]. Modulation of the Gut Microbiota for Human Health Benefits Past and current research has demonstrated that the gut microbiota plays an important role in the pathogenesis of a number of diseases. Probiotics have also been investigated as a method of treatment for IBD. we describe the use of probiotics on colorectal cancer. was effective at reducing tumor incidence in the rat DMH colon cancer model [95]. F. Studies using Bifidobacterium longum also demonstrated an inhibition of carcinogen-induced colon cancers and precursor lesions [96. A study was undertaken with hypercholesterolemic mice administered low levels of the probiotic Lactobacillus reuteri for a week [101]. Certain bacteria. Early studies suggest that probiotic bacteria may have a beneficial effect on hypercholesterolemic patients. the modulation of the gut microbiota could potentially decrease hypercholesterolemia in affected patients. by decreasing blood lipid levels [101]. by impacting the emulsification. hypercholesterolemia and NAFLD. Another study demonstrated the use of Faecalibacterium prausnitzii as a probiotic for treating Crohn’s Disease (CD) [36]. Early studies demonstrated that 1. described in another review. The mice demonstrated a decrease in cholesterol and triglyceride levels and an increase in the HDL : LDL ratio [101].” such as Bifidobacteria and Lactobacilli. In this section. these patients showed. are shown to be correlated with a decrease in the occurrence of a number of disorders. 4. suggesting that the targeted increase of these beneficial bacteria could decrease the incidence and severity of prominent diseases. Probiotics have been proposed and investigated as a potential treatment/prevention method for colorectal cancer. associated with a modulation of the microbiota” [55].4 levels of non-HDL cholesterol [53]. Following treatment. Modulation of the Gut Microbiota by Probiotics Can Promote Human Health. so. Probiotics are inexpensive. absorption. digestive. The most common types of probiotic microorganisms are the lactic . probiotics. The probiotics are suggested to achieve a protective effect by interacting with the carcinogen(s) in the intestinal lumen (in the case of the DMH rat model. by the modification of bile acid metabolic patterns. Prebiotic delivery nonspecifically increases the number of “good bacteria” not acting at the species level. probiotics are a method by which the gut microbiota can be specifically modulated for an individual to reestablish and maintain a healthy state. free of long-term negative side-effects. have been done.3% of the patients in the control group suffered a disease relapse compared to only 20% of the patients administered the probiotic capsule [99]. which may be important in some disease states. Numerous prebiotics have demonstrated their beneficial effects on disease through modulators of the gut microbiota [57–61]. The colonic delivery of prebiotics and probiotics are methods that have been successfully used to modify the gut microbiota. An important concern is the development of bacterial resistance which reduces the effectiveness of the therapy and further predisposes the patient to life-threatening illnesses caused by potential pathogens with increased resistance to the antibiotic. Furthermore.

in both murine and human trials. Lactobacillus bulgaricus. including TNF-α [105]. (3) nutrient competition and production. Lactobacillus plantarum. (2) by the blocking of pathogenic bacteria adhesion sites. VSL#3 is a high-potency medical food probiotic made up of a number of different bacterial strains [106]. (3) by nutrient competition and production. These strains make up 450 billion live lactic acid bacteria per packet: Bifidobacterium breve. Bifidobacterium infantis. (5) by the modulation of immune responses [104]. improvement of the function of the epithelial barrier and direct decreases of proinflammatory cytokines. (4) by the degradation of toxins and toxin receptors. The mechanisms include (1) by the production of pathogen inhibitory substances. and Streptococcus thermophilus [106]. . Studies have also demonstrated that the delivery of certain strains of Lactobacilli can alleviate symptoms associated with IBD [103. This combination. Probiotics can have an inhibitory impact on the development of NAFLD by a number of mechanisms: competitive inhibition of pathogenic bacterial strains. They can influence human health by (1) production of pathogen inhibitory substances. demonstrated all of the mechanisms described as potential beneficial targets for the treatment of NAFLD [107]. Lactobacillus paracasei. (4) degradation of toxins and toxin receptors. (2) blocking of pathogenic bacteria adhesion sites. Murine models of acute liver injury have also shown a decrease in hepatic injury following the administration of various Lactobacillus and Bifidobacterium species [108–110]. (5) modulation of innate immune responses.Journal of Biomedicine and Biotechnology 5 (1) Production of pathogen inhibitory substances (2) Blocking of pathogenic bacterial cells adhesion sites (3) Nutrient competition and production Gut lumen (4) Degradation of toxins and toxin receptors (5) Modulation of the immune responses Mucous layer Gut epithelium Bloodstream Probiotic bacteria Potentially pathogenic bacteria Inhibitory substances Nutrients Toxin receptors Toxins Antibodies Antigen presenting cells Figure 2: Pathways by which a probiotic can positively influence human health. Lactobacillus acidophilus. There are a number of mechanisms by which probiotics could be exerting their beneficial effects. as shown in Figure 2. alteration of the inflammatory effects of pathogenic strains through changes in cytokine signalling. Probiotics have also been proposed as a potential treatment option for NAFLD because of their modulating effect on the gut flora that could influence the gut-liver axis towards a healthy state. LDL [102]. 104]. Bifidobacterium longum. NAFLD is characterized by the release of inflammatory cytokines and commensal bacteria have been shown to provoke anti-inflammatory responses from the gut epithelia. suggesting a mechanism of action to treat the disease [105].

controlled release. starch polyanhydrides. enzyme retrieval. A delivery system is. alginate-poly-L-lysine.2. determined by its molecular weight. There are many methods available. extracted from brown algae. There exists a great variety of microcapsules which can differ in size. one prominent difficulty encountered with the use of alginate beads is that these. including formulations using carrageenan. Alginate is an unbranched polysaccharide which contains 1. and enteric coated polymers [116]. microcapsules can have an assortment of objectives and applications. depending on the final goal of the encapsulated product. It is a polycationic polymer that can be used during the coating step of microencapsulation. alginate and poly-L-lysine (PLL). This paper introduces microencapsulation and discusses its potentials and limitations in bacterial cell delivery to the GIT. This type of microcapsule has been used for many applications including drug. proteins. shown in Figure 3 [87. β-L-mannuronic acid-α-L-guluronic acid blocks [120]. The research group demonstrated that immobilized cells survived significantly better than free cells after refrigeration in pasteurized yogurt for a period of 5 weeks [84]. as detailed in Table 1. are not acid resistant and upon exposure to the low pH conditions encountered in the stomach. Microencapsulation and Delivery of Probiotics Microencapsulation is a method defined as the “entrapment of a compound or a system inside a dispersed material for its immobilization. and bacterial cell delivery. polymethacrylates. A number of methods utilizing polymer cross-linking have been suggested. One newly developed type of microcapsule that shows promising results in terms of mechanical stability and pH resistance is the genipincrosslinked-alginate-chitosan (GCAC) microcapsule. Sun and Griffiths investigated the use of acid-stable beads made of gellan and xanthan gum for the immobilization of Bifidobacterium [84]. display significant shrinkage and a decrease in mechanical strength [64]. Alginate is a naturally occurring biocompatible polymer. 5. liquids. With such a range of substances that can be entrapped. for the delivery of live probiotic bacteria. Probiotics must be delivered to the target sites in sufficient number and metabolic active phase to be effective.4 -linked β-D-mannuronic acid and α-L-guluronic acid blocks which are interdispersed with regions of the alternating structure. There are a number of microcapsule delivery systems that have been proposed for the oral delivery of live bacterial cells. Microencapsulation methods are still being developed and optimized to allow for increased gastrointestinal survival and immunoprotection. drugs. System for Delivering Probiotics to the GIT. One common encapsulation method. each with its own limitations. Another complication is the presence of an immune system which can be induced and potentially attack the delivered cells. composition. alone. structuration and functionalization” [111]. Currently available probiotic formulations are excellent but have serious limitations. Microcapsules can be used to entrap all sorts of substances: solids. with the presence of acids and bile greatly hindering the viability of the probiotics as they travel through the gut (specifically the acidic environment of the stomach). . PLL is a polypeptide made up of the amino acid L-lysine that is available in a variable number of chain lengths. protection. that is increasingly being used in the biotechnology industry for a wide range of applications [119]. The alginate bead could not withstand the harsh conditions of the GIT in the absence of PLL. artificial cell and artificial organ delivery or. and so forth [112–114]. hence. stem cells. and function. Hence. The addition of this polymer leads to the formation of a capsule membrane that provides selective permeability and immunoprotection. utilizes calcium alginate as a polymer [115]. a method is required to protect the probiotic cells while maintaining high levels of probiotic viability and activity when delivered in the GIT. One of the most commonly utilized and characterized formulations for microencapsulation is the alginate-polyL-lysine-alginate (APA) microcapsule [118]. 117]. This method relies on a polyelectrolyte complexation mechanism for the association of the polymers. which provides it with an increased mechanical stability. One of the major limitations is the delivery of probiotics to the lower GIT. bacterial cells. (a) Alginate-Poly-L-Lysine (APA) and (b) Genipin Crosslinked Alginate Chitosan (GCAC) microcapsules.6 1–1000 μm Journal of Biomedicine and Biotechnology Poly-L-Lysine Alginate core containing bacterial cells Genipin crosslinked chitosan (a) (b) Alginate coat Figure 3: The concept of microcapsules for probiotic delivery. whether for drug delivery. required to surpass this obstacle. However. for viable cell immobilization. as described in this review. stem cell. 4.

reuteri Alginate-cellulose B. lactis Alginate-chitosan L. microcapsules containing bacterial cells have been developed as a cholesterol lowering therapy. This enzyme contributes to the deconjugation of bile salts in the intestine [121]. followed by a number of physical or chemical processes [111]. The final step of microencapsulation involves product stabilization through coating. lactis L. longum granules-amylose B. lactis diisocyanate Gellan-alginate B. Early research has demonstrated that certain Lactobacilli have a bile salt hydrolase (BSH) enzyme which can contribute to a significant cholesterol lowering effect in vivo in cardiovascular diseases [121]. plantarum Alginate Beads L. there was a statistical difference between the control and treatment groups following analysis of the small intestine number of adenomas and gastrointestinal intraepithelial neoplasias [29]. no statistically significant difference was observed between the treatment and control group in terms of the number of large intestinal (colonic) adenomas [29]. Unfortunately. The potential antitumorigenic properties of a microencapsulated formulation of L. rhamnosus B. Research into the applications of microencapsulated probiotics is also ongoing. such as spraying or emulsification. casei Alginate-chitosanB. acidophilus L. On a more positive note. infantis L. emerged as a potential mechanism for inducing cholesterol lowering. These preliminary results suggest that microencapsulated probiotic bacteria could have a role in the development of a successful colon cancer therapeutic. The first step is the incorporation of the ingredients into a solution by mixing or dispersion. 93] There are a number of different methods used to fabricate microcapsules. infantis B. [76–78] [79–81] [82] [83] [84–86] [87] [88] [89] [90. lactis Reference(s) 7 one wants to obtain. 6. animalis subsp. The oral delivery of Lactobacillus has. This is then followed by mechanical operations. longum Gelatin-toluene-2-4L. 6. longum L. salivarius L. Recently. bulgaricus Alginate-chitosan-AcrylB. demonstrated that microencapsulated BSH-active bacteria are able to survive in a simulated human gastrointestinal model while maintaining cell viability and enzyme activity. pseudolongum B. described in the following section. 91] [92. which would not be possible with the direct delivery of nonmicroencapsulated bacterial cells [75]. Martoni et al. bifidum alginate L. The characteristics of the microcapsule must also take into consideration the function that the microcapsule will ultimately undertake. Research has shown that microencapsulated probiotics keep their viability better than free cells under stress in GIT deliveries. The mice were gavaged APA microcapsules of L. acidophilus over a period of 12 weeks followed by the enumeration. longum L. 75] 6. lactis Sureteric B. bulgaricus S. therefore. bifidum B. animalis subsp. infantis arabic-soluble starch B. The microencapsulation technique employed is determined by the type and the size of microcapsules . [64–70] [71] [72.2. to make up the core of the microcapsule. casei L. There are generally three main stages to the process of microencapsulation. Microencapsulated Probiotics There has been strong interest in the field of microencapsulated probiotics. Microencapsulated Probiotics and Colon Cancer. paracasei L. thermophilus κ-carageenan L. acidophilus Potato starch B. acidophilus were studied in Min (multiple intestinal neoplasia) mice carrying a germline Apc mutation which spontaneously develop numerous pretumoric intestinal neoplasms [29]. lactis acetate phthalate L. with promising results for the eventual treatment of a number of disorders. bifidum B. rhamnosus B. acidophilus B. casei Gelatin-gum B. lactis B. Each step of microencapsulation can be optimized according to the desired characteristics of the final formulation. reuteri alginate L.Journal of Biomedicine and Biotechnology Table 1: Types of microcapsules available for the targeted delivery of probiotic bacteria. casei B. the classification and the histopathology of adenomas [29]. 73] [72] [64] [72] [74] [64.1. plantarum alginate-chitosan B. longum S. lactis Pectin-casein L. longum Genipin-crosslinkedL. lactis Eze Alginate-chitosanB. adolescentis Alginate-coated gelatin B. to form the droplets. bifidum Alginate-poly-L-lysineL. breve Whey protein B. Microencapsulated Probiotics for Use in Cardiovascular Diseases. adolescentis B. breve Gellan-xanthan B. animalis subsp. acidophilus B. Types of Microcapsules Bacteria L. lactis Alginate-starch B.

acidophilus had an inhibitory effect on colon tumorigenesis showed that the amount of probiotic colonization of the GIT is directly linked to the rate of inhibition of tumorigenesis [98]. at a cost-effective level. and synbiotics have shown great potential for the treatment of a number of disorders. Most of the probiotics are strain specific. only 1% survive the gastric transit. a number of issues concerning the formulation of a microencapsulated probiotic still need to be addressed before a successful product can be developed. LDL cholesterol. 7. R.36%. As described before.8 Another microencapsulated probiotic Lactobacillus demonstrated cholesterol lowering capabilities in hypercholesterolemic animals. Lactobacillus fermentum. This composition variability also gives rise to potential difficulties in terms of the use of animal models for the investigation of probiotic formulations. Nevertheless. to be effective at reducing colon tumorigenesis. therapeutic probiotic microorganisms must remain viable in vivo [123]. no. Turnbaugh. As aforementioned. there are still a number of challenges that remain to be addressed before they can be successfully used to treat/prevent disorders. the support of the Industrial Innovation Scholarship (IIS) BMP Innovation—NSERC. 1476–1483. [2] P. “Obesity and the microbiota. cell viability and retention of metabolic activity of the encapsulated bacterial cells requires further development for specific bacterial strains and diseases. Guarner and J. [5] H. the industry scale production of microencapsulated probiotics. It has been shown that.” Nature. 9356. M.. Knight.40%. M. FQRNT and Micropharma Limited to C. Cani. vol. Salminen. . 1546–1558. Journal of Biomedicine and Biotechnology for their suitability and efficacy in proper animal models and human clinical trials. A targeted welldefined formulation should be developed in which microencapsulation will play a critical role. albeit with a different mechanism of action involving a feruloyl esterase enzyme [122]. and investigation of formulation stability. the administration of bacteria from the same species but of different strains resulted in noncomparable effects. 2003. As mentioned earlier. Microencapsulation has provided a significant advancement in the field. they therefore must be developed and characterised in vitro and evaluated References [1] P. Prakash. the literature suggests that probiotics will lead to efficient therapeutic formulations for the treatment and/or prevention of a number of animal and human health disorders. Challenges and Future Outlooks The gut microbiota is a complex system that has been shown to influence health.” Current Pharmaceutical Design. and the NSERC Undergraduate Student Research Award to Arielle Cantor. a feruloyl esterase active bacterium. T. there can be contradicting results as to the beneficial effect of probiotics on the microbiota of the GIT. for a period of 18 weeks [122]. microencapsulation could prove beneficial in increasing efficacy.59% lower. was microencapsulated and delivered to hypercholesterolemic hamsters twice daily by oral gavage. pp. 512–519. rigorous in vitro and in vivo animal and human clinical studies are needed to demonstrate the efficacy and the long-term safety of microencapsulated and other probiotic formulations. R.” The Lancet. supplement 1. 449. Duchesneau. Hamady. Histological studies were also performed and demonstrated that the microencapsulated probiotic reduced the progression of atherosclerotic lesions in the test animals [122]. Kaser. 2009. R. 15. “The human microbiome project. 13. 5. Furthermore. allowing for the delivery of a greater number of viable bacteria to the GIT. C. pp. [4] S. E. Furthermore. pp. The variability in experimental design poses a great challenge in probiotic research that must be addressed properly. The elucidation of the mechanism of action of the probiotic would allow for a better selection process. no. no. This probiotic formulation was hence shown to be effective at managing excessive serum cholesterol and triglyceride levels [122]. A. 804–810. There are excellent trials available that demonstrate the efficacy of these formulations but safety is an issue that remains to be investigated. “Functional food science and gastrointestinal physiology and function. The process and methods for microencapsulation require further investigations and optimization. each varying in efficiency and application. Boutron et al. a specific mechanism of action must be developed for each application so that an evidence-based probiotic formulation can be designed that can potentially compete with well-articulated and welldeveloped drug formulations. 7164. M. D. 31. 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