International Journal of Nutrition, Pharmacology, Neurological Diseases

REVIEW ARTICLE
Year
: 2014  |  Volume : 4  |  Issue : 1  |  Page : 11--22

Clinical significance of probiotics in human


Diksha Jain, Hotam Singh Chaudhary 
 Department of Biotechnology, Madhav Institute of Technology and Science, Gwalior, Madhya Pradesh, India

Correspondence Address:
Hotam Singh Chaudhary
Department of Biotechnology, Madhav Institute of Technology and Science, Gwalior- 474 005, Madhya Pradesh
India

Abstract

This review gives a glimpse of probiotic role in human life and how it affects the individual. Probiotics have been studied as an alternative to antibiotic therapy. The term DQprobioticsDQ comes from the Greek word DQpro biosDQ meaning DQfor lifeDQ opposed to DQantibiotics,DQ which means DQagainst life.DQ As the research is progressing, new approaches to treat diseases are being developed such as prebiotics and synbiotics. Probiotics work in our body through various modes of action, namely, production of inhibitory substances, stimulation of immunity, affecting host gene expression, blocking of adhesion sites, competition for nutrients, and degradation of toxin receptors. The various criteria employed to select strains for probiotics are acid-bile stability, adhesion stability, antimicrobial activity, viability and stability during processing and storage. Research has proved the therapeutic effects of probiotics in diseases such as diarrhea, rotavirus diarrhea, irritable bowel syndrome, Helicobacter pylori infection, hepatic encephalopathy, celiac disease, and hyperoxaluria. Probiotics have prophylactic effects in diseases such as pouchitis and ulcerative colitis that come under inflammatory bowel disease, antibiotic-induced diarrhea, necrotizing enterocolitis, ventilator-associated pneumonia, dental decay, periodontal infection, halitosis, constipation, gastrointestinal infections, and colon cancer. Probiotics also help in xenobiotic metabolism, lactose intolerance, cholesterol reduction, sucrase-isomaltase deficiency, stress, and hypertension. Further research is needed to prove the efficacy of probiotics in case of radiation-induced diarrhea, HIV/AIDS diarrhea, CrohnSQs disease, nonalcoholic fatty liver disease, and allergy.



How to cite this article:
Jain D, Chaudhary HS. Clinical significance of probiotics in human.Int J Nutr Pharmacol Neurol Dis 2014;4:11-22


How to cite this URL:
Jain D, Chaudhary HS. Clinical significance of probiotics in human. Int J Nutr Pharmacol Neurol Dis [serial online] 2014 [cited 2019 Jul 22 ];4:11-22
Available from: http://www.ijnpnd.com/text.asp?2014/4/1/11/124610


Full Text

 Introduction



Elie Metchnikoff was the first to postulate that lactic acid bacteria (LAB) had potential of providing health benefits and also promote longevity. [1] Numerous in vivo and in vitro studies have shown that our very own normal intestinal flora is capable of protecting us against pathogenic and opportunistic microorganisms. [2]

There is an apprehension that pharmaceutical industry will no longer be able to develop effective antibiotics at a rate sufficient to compete with the emergence of microbial resistance to old antibiotics. Thus interest increased toward feeding beneficial microorganisms to humans as an alternative to antibiotic therapy. Probiotics provide an attractive alternative treatment because antibiotics that further delay recolonization by normal colonic flora can be avoided. [3] Probiotics are defined as "live microorganisms, which confer a health benefit on the host when administered in adequate amounts." [4],[5] The term "probiotics," was introduced in 1965 by Lilly and Stillwell. [6] Yakult was the first commercially available probiotic drink, introduced in Japan in 1935. It was then followed by Activia, introduced in France in 1987. People started giving importance to probiotic foods after 2006 and the market of these products increased rapidly in the world, along with other fermented dairy products. Researchers also used other foods as vectors to introduce probiotics to humans. [7]

The groups that can be benefitted from the use of probiotics and prebiotics in their regular diet include the following:

Infants (eg., to prevent diarrhea, allergy)Toddlers (eg., prevention of upper respiratory tract infections)Teenaged girls (bone mass)Pregnant women (atopic disease, bone mass)Adults with acute symptoms (eg., with functional gastrointestinal symptoms)Elderly (eg., to cope with decreasing immunity)Athletes (eg., restoration of immune system)Travelers (eg., to prevent diarrhea). [8]

Probiotics also have been used prophylactically and/or therapeutically in which the role of disruption of normal flora in the disease process is less clear.

 Prebiotics and Synbiotics Additional Approach to Probiotics



Prebiotics is an additional approach, which boosts up the effect of probiotics. Prebiotics are dietary substances (mostly consisting of nonstarchy polysaccharides and oligosaccharides) that nurture a selected group of microorganisms living in the gut. They favor the growth of beneficial bacteria over that of harmful ones. Often prebiotics are used as food ingredients in biscuits, cereals, chocolate, spreads, and dairy products. Commonly known prebiotics are oligofructose, inulin, galacto-oligosaccharides, lactulose, and breast milk oligosaccharides. A possible side effect of prebiotics intake is intestinal discomfort from gas production. [9],[10],[11]

On the other hand, synbiotics are appropriate combinations of prebiotics and probiotics. A symbiotic product exerts both a prebiotic and probiotic effect. [12]

Microorganisms involved in probiotics

Refer to [Table 1].{Table 1}

Modes of action

The probiotic bacteria fight against pathogenic bacteria through various ways. Some of which are explained below:

For schematic representation of the mode of action of probiotics in the intestines refer to [Figure 1]. [36]{Figure 1}

Production of inhibitory substances

Probiotic bacteria produce variety of substances, including organic acids, hydrogen peroxide, and bacteriocins, which are inhibitory to both gram-positive and gram-negative bacteria. These compounds may reduce not only the number of viable cells but may also affect bacterial metabolism or toxin production. [3] Production of lactic acid lowers the pH, which inhibits the development of pathogenic bacteria. Secretion of hydrogen peroxide has an inhibitory effect on growth and development of Escherichia coli 0157: H7. [37] Supernatants derived from Lactobacillus rhamnosus Lcr35 cultures are an inhibitor on nine types of pathogenic bacteria: E. coli (ETEC), E. coli (EPEC), Klebsiella pneumoniae, Shigella flexneri, Salmonella typhimurium, Enterobacter cloacae, Pseudomonas aeruginosa, Enterococcus faecalis, and Clostridium difficile. [38]

Stimulation of immunity

Probiotics stimulates specific and nonspecific immunity and helps in protection against intestinal diseases. [23],[39],[40],[41],[42],[43],[44] Patients treated with peroral administration of Lactobacillus GG during acute rotavirus diarrhea associated with an enhanced immune response to rotavirus and facilitate the shortened course of diarrhea. [40] Various cytokines were secreted by the administration of L. casei Shirota, [45] L. rhamnosus HN001, and Bifidobacterium lactis HN019 (stimulates the secretion of IL-12), which enhanced the cytotoxicity of lymphocytes. [4]

Affecting host gene expression

Human genome arrays now provide a means to study the effect of the introduction of a probiotic organism on host gene expression. Such systems can document changes in differential gene expression. [46] For example, the turning on of mucin expression by Lactobacillus sp. [47] and by activating transcription factors involved in cytokine signaling directly, leading to NF-κB activation, and indirectly via cytokines, leading to signal transducer and activator of transcription activation. [48]

The studies showing that Bacteroides thetaiotaomicron induces angiogenesis and development of a healthy intestine further illustrates the importance of the host-commensal interaction. [49] Newborns fed with L. rhamnosus GG resulted in a reduced incidence of atopy. [50]

Although the primary focus has been on communication related to virulence and disease, there is evidence now emerging that probiotic Lactobacillus, such as Lactobacillus reuteri RC-14, produce signaling molecules that interfere with gene expression in other organisms. [8] One method of communication involves molecules called autoinducers that are secreted by organisms to regulate gene expression and control behavior on a community-wide scale. [51] A study showed that the determinants for pheromone binding and specificity are contained within the transmembrane domain of Lactobacillus plantarum. [52] In many lactic acid bacterial strains, bacteriocins function as quorum sensing molecules, in that they are produced, and are controlled in a cell-density dependent manner, using a secreted peptide-pheromone that can enable the organism to switch on bacteriocine production at times when competition for nutrients is likely to become more severe. [53]

Blocking of adhesion sites

Competitive inhibition for bacterial adhesion sites on intestinal epithelial surfaces is another mechanism of action for probiotics. [54],[55],[56] Consequently, some probiotic strains have been chosen for their ability to adhere to epithelial cells. [3]

Competition for nutrients

Probiotics may utilize nutrients otherwise consumed by pathogenic microorganisms. However, the evidence that this occurs in vivo is lacking. [3]

Degradation of toxin receptor

The postulated mechanism by which S. boulardii protects animals against C. difficile intestinal disease is through degradation of the toxin receptor on the intestinal mucosa. [57],[58],[59]

Selection criteria

The criteria used to select probiotics define the optimal quality control of probiotic strains in industrial practice. Important quality control properties that must be constantly controlled and optimized are the following: Adhesive properties; bile and acid stability; viability and survival throughout the manufacturing process; affects on carbohydrate, protein, and fat utilization; and especially, colonization properties and immunogenicity. Most of these properties are related to the physiologic properties of the strain, but long-term industrial processing and storage conditions may influence probiotic properties. Thus, in addition to technologic properties, functional properties should be considered in quality control measures. [60],[61],[62],[63],[64],[65],[66],[67]

Acid and bile stability

To survive passage through the oral cavity, stomach, and small intestine, probiotic strains must tolerate the lysozyme, the acidic and protease-rich conditions of the stomach, and survive and grow in the presence of bile acids. Simple in vitro tests can be used for selection of acid- and bile-tolerant strains to ensure the quality of probiotic cultures during manufacture and storage and throughout the shelf life of the product. In vivo validation of survival through the human stomach is difficult to obtain. [60],[68],[69]

Adhesion stability

Adhesion characterization is an important quality control method for assessing the surface structure of probiotic bacteria and related gut barrier effects. In several studies, adhesion was related to a shortening of duration of diarrhea, immunogenic effects, competitive exclusion, and other health effects. [44],[67],[70],[71] Adhesion of probiotic strains is variable. Adhesion in different in vitro models varies even within the same strain and differences between strains can be significant. [72],[73],[74] Adhesion of some common probiotic strains was studied by using a human colon carcinoma cell line (Caco-2) and human ileostomy glycoproteins as in vitro models for intestinal epithelium and mucus, respectively. [60],[74],[75],[76],[77],[78],[79]

Antimicrobial activity

Antimicrobial activity targets the enteric undesirables and pathogens. [80] Production of bacteriocins is highly affected by the factors of the species of microorganisms, ingredients and pH of medium, incubation temperature and time. Antimicrobial effects of lactic acid bacteria are formed by producing some substances such as organic acids, carbon dioxide, hydrogen peroxide, diacetyl, low molecular weight antimicrobial substances such as reuterin, and bacteriocins such as nisin A, cytolysin, plantarisin S, and acidophilucin A. [81],[82],[83]

Viability and properties during processing and storage

Definition of a probiotic includes viability as an important factor. [20],[84] It is important to take viability into account because many strains exert effects in the nonviable form as well. [85],[86] The viability of several strains in fermented milks is dependent on both the production method and the strain. It is possible that cultures producing organic acids, diacetyl, or other inhibitory compounds in the fermented milk may influence the survival of some probiotic cultures. The production method for fermented milk needs to be carefully evaluated to offer consumers the right amount of viable cultures to obtain the reported health effects. [60]

Clinical applications

Diarrhea

Treatment of acute diarrhea: It has been confirmed that different probiotic strains, including L. reuteri ATCC 55730, L. rhamnosus GG, [87] L. casei DN-114 001, and Saccharomyces cerevisiae (boulardii) are useful in reducing the severity and duration of acute infectious diarrhea in children. The oral administration of probiotics shortens the duration of acute diarrheal illness in children by approximately 1 day. Several meta-analyses of controlled clinical trials have been published that show consistent results in systematic reviews, suggesting that probiotics are safe and effective. The evidence from studies on viral gastroenteritis is more convincing than the evidence on bacterial or parasitic infections. Mechanisms of action are strain specific: There is evidence for efficacy of some strains of lactobacilli (eg., Lactobacillus casei GG and Lactobacillus reuteri ATCC 55730) and Saccharomyces boulardii. The timing of administration is also of importance. [27]

Antibiotic-induced diarrhea

Diarrhea is the most common side effect of antimicrobial therapy, with about 20% of patients receiving an antibiotic developing this condition. [88] The yeast S. boulardii has been successfully used in the prevention of antibiotic-associated diarrhea. [89],[90] Recent research has indicated that L. casei DN-114 001 is effective in hospitalized adult patients for preventing antibiotic-associated diarrhea and C. difficile diarrhea. [27] In a prospective, double-blind, placebo-controlled study, 180 hospitalized patients receiving antibiotic therapy were treated concurrently with either placebo or S. boulardii. The overall incidence of diarrhea in these patients was 26%; 22% of the patients receiving placebo developed diarrhea compared with 9% of patients receiving S. boulardii, a statistically significant difference. [91]

Radiation-induced diarrhea

There is inadequate research evidence to be certain that VSL#3 (L. casei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. breve, B. infantis, and Streptococcus thermophilus) is effective in the treatment of radiation-induced diarrhea. [27]

Rotavirus diarrhea

Lactobacillus has demonstrated some promise as a treatment for rotavirus infection. [40],[92],[93] In a study 74 children (age 4-5 months) with diarrhea were treated with either Lactobacillus GG or placebo. Approximately 80% of the children with diarrhea were positive for rotavirus. The investigators demonstrated that the duration of diarrhea was significantly shortened (from 2.4 to 1.4 days) in patients receiving Lactobacillus GG. The effect was even more significant when only the rotavirus-positive patients were analyzed. [94]

HIV/AIDS diarrhea

Diarrhea is a very serious consequence of human immunodeficiency virus (HIV) infection. The etiology of this diarrhea is frequently unknown and there are no effective treatment modalities. However, S. boulardii was used to treat 33 HIV patients with chronic diarrhea. [95],[96] In these double-blind studies, 56% of patients receiving S. boulardii had resolution of diarrhea compared with only 9% of patients receiving placebo.

Irritable bowel syndrome

In a systematic review of several randomized controlled trials, Bifidobacterium infantis 35624 was the only probiotic to provide significant improvement in irritable bowel syndrome (IBS) symptoms. [97] L. reuteri may improve colicky symptoms within 1 week of treatment, as shown in a recent trial with 90 breastfed babies with infantile colic. In summary, there is literature suggesting that certain probiotics may improve the principal symptoms in persons with IBS. [27]

Ventilator-associated pneumonia

A meta-analysis of 12 randomized controlled trials found significant reductions in the rate of ventilator-associated pneumonia, intensive care unit (ICU) length of stay, and colonization of the respiratory tract with Pseudomonas aeruginosa but no significant reduction in ICU mortality, hospital mortality, or hospital length of stay. [98]

Helicobacter pylori infection

Lactobacillus has been shown to be antagonistic to H. pylori both in vitro and in a gnotobiotic murine model. [99],[100],[101] A recent meta-analysis of 14 randomized trials suggests that supplementation of anti-H. pylori antibiotic regimens with certain probiotics may be effective in increasing eradication rates and may be considered helpful for patients with eradication failure. [27]

Hepatic encephalopathy

Investigators have postulated that it may be possible to use probiotics to decrease intestinal urease activity. For example, patients treated with Lactobacillus acidophilus and neomycin show a greater decrease in fecal urease activity than in patients treated with neomycin alone. [102],[103],[104] The decreased fecal urease activities corresponded to lower serum ammonia levels and improvements in the clinical status of patients. [3]

Prebiotics such as lactulose are commonly used for the prevention and treatment of this complication of cirrhosis. Minimal hepatic encephalopathy was reversed in 50% of patients treated with a synbiotic preparation (four probiotic strains and four fermentable fibers, including inulin and resistant starch) for 30 days. [27]

Inflammatory bowel disease

Pouchitis

There is good evidence for the usefulness of probiotics in preventing an initial attack of pouchitis (VSL#3), and in preventing further relapse of pouchitis after the induction of remission with antibiotics. Probiotics can be recommended to patients with pouchitis of mild activity, or as maintenance therapy for those in remission. [27] Investigators have also postulated that Lactobacillus GG may be an effective therapeutic agent for pouchitis because it does not demonstrate mucus-degrading properties. [105]

Ulcerative colitis

A study on a randomized, double-blind clinical trial with 120 ulcerative colitis (UC) patients reported that oral administration of E. coli strain Nissle 1917 as a maintenance treatment of remission showed no difference in relapse rates compared with patients on mesalazine. [29] From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of UC. [3] These results were confirmed by another study. [30]

Crohn's disease

A study reported that in pediatric Crohn's disease (CD), consumption of Lactobacillus GG was associated with increased gut IgA levels, which could promote the gut immunological barrier. [23] VSL#3, a mixture of four Lactobacilli strains (L. plantarum, L. casei, L. acidophilus, and Lactobacillus delbrueckii ssp. bulgaricus), three Bifidobacteria strains (Bifidobacterium infantis, Bifidobacterium breve, and Bifidobacterium longum), and one strain of Streptococcus salivarius ssp. thermophilus, has been examined in UC, CD, and pouchitis patients. A study demonstrated the efficacy of this probiotic mix in maintenance of remission in patients with chronic pouchitis. [106] Although the trials summarized above are promising, the current consensus is that a number of larger controlled trials are necessary before the use of probiotics as a routine medical treatment is warranted. [107]

Non-alcoholic fatty liver disease

The human and animal studies have revealed an affirmative effect of probiotics supplementation on markers of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). [108],[109],[110],[111],[112],[113] The general effect of probiotics in this regard seem to be related to reducing the impact of pathogenic bacteria on NAFLD development by exclusion or inhibition of invading bacteria, as well as by producing antimicrobial factors such as short-chain fatty acids (SCFA). [114] SCFA can also help by modifying the epithelial permeability. [115],[116],[117]

Necrotizing enterocolitis

Clinical trials have shown that probiotic supplementation reduces the risk of necrotizing enterocolitis (NEC) in preterm neonates of less than 33 weeks gestation. Several meta-analyses [118],[119],[120] have shown to reduce the relative risk of NEC and death when Bifidusbacterium spp. and L. acidophilus are used prophylactically in neonates with birth weight <1500 gm. Among neonates with birth weights <750 gm, there was an increase in the risk of sepsis with the use of probiotics. [121] In summary, there is strong support for the use of certain probiotic strains in preterm infants. [27]

Celiac disease

Research into the use of probiotics as an adjuvant strategy to the gluten-free diet is underway in order to improve the quality of life of celiac disease patients. The strain B. longum CECT 7347 has been demonstrated to ameliorate damage caused by celiac disease, in both in vitro and in vivo animal models. [122],[123],[124] Once the efficiency of the strain has been demonstrated, given its potential in vivo functionality, a complete safety assessment is also required. [125]

Dental decay

It should also be noted that most probiotics are in dairy forms containing high calcium, possibly reducing demineralization of teeth. Probiotics should adhere to dental tissues to establish a cariostatic effect and thus should be a part of the bio-film to fight the carcinogenic bacteria. [5] L. rhamnosus GG and L. casei have proved their potential to hamper growth of oral streptococci. [126]

Periodontal infection

Clinical studies where probiotic species have been investigated specifically from a periodontal disease perspective are sparse. [5] L. reuteri and Lactobacillus brevi are among the species able to affect gingivitis and periodontitis. [127] According to a study, high levels of Lactobacillus in microbiota caused an 82% and 65% inhibition in porphyromonas gingivalis and prevotella intermediate growth, respectively. [128]

Halitosis

Regular use of probiotics can help to control halitosis. After taking Weissella cibaria, reduced levels of volatile sulfide components produced by Fusobacterium nucleatum. [129] The effect could be due to hydrogen peroxide production by W. cibaria, causing F. nucleatum inhibition. [5]

Constipation

Zyactinase, a freeze-dried extract of Kiwifruit (Actinidia deliciosa), has been developed as a constipation relief product as well as for long-term gut health. Zyactinase contains a protease complex, fiber, pectin, and fructo-oligosaccharides. Clinical studies have proved that zyactinase stimulates increased bowel movements and relieves the symptoms of IBS. This was proposed to be partially due to the stimulation of the gut microflora. Zyactinase was found to significantly increase the growth of probiotic bacteria such as L. reuteri, L. acidophilus, Pediococcus acidilactici and Lactobacillus planetarium in comparison to isomalt. Zyactinase was also found to significantly inhibit the growth of E. coli and Salmonella typhimurium with almost significant inhibition of Staphylococcus aureus. However, zyactinase stimulated the growth of Listeria monocytogenes. [130]

Gastrointestinal infections

Campylobacter enteritis causes the most common gastrointestinal infection. Results suggest that the administration of B. breve plays an important role in restoring the normal intestinal flora and thus shortens the time needed to eradicate Campylobacter. Epidemiological result suggests that B. breve yoghurt may be useful for prophylaxis of infectious diarrhea rather than for therapeutic use. [131]

Hyperoxaluria

Normally, the intestinal tract is colonized with bacteria such as Oxalobacter formigenes, Lactobacillus species, and others. [132],[133] Intestinal oxalate-degrading bacteria are capable of degrading oxalate to CO and formate; the latter is further metabolized and excreted via feces. Thus, treatment with oxalate-degrading bacteria could be a new therapeutic option in patients with hyperoxaluria and calcium oxalate stone disease. A recombinant L. plantarum WCFS1 (L. plantarum) secreting heterologous oxalate decarboxylase (OxdC) was developed, which may provide possible therapeutic approach by degrading intestinal oxalate. The results showed secretion and functional expression of OxdC protein in L. plantarum driven by signal peptides Lp 0373 and Lp 3050. The recombinant strain showed up to 50% oxalate reduction in medium containing 10 mM oxalate. [134]

Cancer

A study advanced the theory that the "internal environment" of the intestinal tract may affect cancer rates, especially colon, breast, and stomach. Transformations of foodstuffs, endogenously produced compounds, or microbial byproducts by the plethora of microbes present in the intestinal tract into harmful substances may lead to the progenesis of different types of cancer. [135]

Colon cancer

The SYNCAN study tested the effect of oligofructose plus two probiotic strains in patients at risk of developing colonic cancer. The results of the study suggest that a synbiotic preparation can decrease the expression of biomarkers for colorectal cancer. [27]

Probiotics have been reported for their inhibitory effect on the expression of COX-2, NF-κB, nitric oxide, and cytokine expression. [136] Overexpression of COX-2 in colonic cells gives colonocytes antiapoptotic potential and cell proliferation ability. The probiotics mixture, VSL#3 includes L. casei, L. plantarum, L. acidophilus, L. delbrueckii subsp. bulgaricus, which could inhibit colonocytes proliferation by inducing proapoptotic pathway by regulation of the concentration of COX-2 in colon. [137] Putaala et al. demonstrated that the probiotics are involved in the inhibition of colon carcinogenesis by the downregulation of COX-2. [138] In another study, Otte et al. showed that probiotics were able to regulate COX-2 gene expression significantly in comparison to heat inactivated probiotics. [136] L. casei shirota induces the NF-κB, STAT3, COX-2, PI3/Akt, and DNA binding activity. [139] Cell-free supernatants of B. lactis 420, L. acidophilus, and L. salivarius were able to modulate the gene expression involved in tight junction and regulate the expression of COX-2 and NF-κB, [138] thus suggesting that probiotics produced bioactive metabolites. Probiotics hence could be able to induce or modify the gene expression in the gastrointestinal tract. Several researches show that probiotics are able to produce natural ligands by their metabolic activity such as conjugated linoleic acid (CLA). [140] CLA is the natural ligands for cell signaling components like PPARγ and has better therapeutic prospect than non-steroidal anti-inflammatory drugs (NSAID) used in cancer.

Xenobiotic metabolism

Bifidobacterium and Lactobacillus have low activities of xenobiotic metabolizing enzymes such as azoreductase, nitroreductase, nitrate reductase, and β-glucuronidase. But they have high levels of glucosidase activity, which may result in the generation of flavonoid aglycones in the gut with genotoxic and anticarcinogenic properties. The evidence suggests that increasing the numbers of lactic acid bacteria in the gut could modify, beneficially, the levels of xenobiotic metabolizing enzymes. [141]

Lactose intolerance

Lactase-positive strains of bacteria (eg, Lactobacillus, Bifidobacterium, and Streptococcus) are commonly added to pasteurized dairy products to increase digestibility of the lactose present in the dairy product. [142],[143],[144] There are two probable mechanisms by which the addition of these bacteria is beneficial, that is, the reduction of lactose in the dairy product through fermentation and the replication of the probiotic in the gastrointestinal tract, which releases lactase. [3]

Cholesterol reduction

Some studies have hypothesized a role for the lactic microflora in systemically reducing blood lipid values. [145] It has been suggested that some probiotics can degrade cholesterol in the gut as well as produce metabolites that interfere with its synthesis in the liver. However, this has not been equivocally proved, and there are contrasting data from human volunteer trials. [9]

Sucrase-isomaltase deficiency

A study used S. cerevisiae to treat eight children with sucrase-isomaltase deficiency. These investigators demonstrated that in children given sucrose followed by S. cerevisiae, there was an improvement in both their hydrogen breath test and gastrointestinal symptoms. The investigators postulated that S. cerevisiae was supplying the missing enzymes. [146]

Stress

Two clinical studies show that Lactobacillus Rosell-52 and Bifidobacterium Rosell-175 allow alleviating physiological and psychological signs of stress and anxiety, without displaying any adverse event. This effect is correlated with biomarker monitoring (urinary-free cortisol) and several animal studies showing behavioral and physiological impact of the probiotic foods. Altogether, these results bring further evidence that gut microflora play a role in stress, anxiety, and depression, perhaps via the enteric nervous system as well as centrally and indicate that probiotics could represent an innovative, effective, and natural solution to cope with stressful situations. [147]

Hypertension

One line of research has suggested that bioactive peptides resulting from the proteolytic action of probiotic bacteria on casein (milk protein) during milk fermentation may suppress the blood pressure of hypertensive individuals. [148] Preliminary studies with spontaneously hypertensive rats [149],[150] and one human clinical study provide the evidence. [151] Two tripeptides, valine-proline-proline and isoleucine-proline-proline, isolated from a dairy-based fermentation of milk by S. cerevisiae and Lactobacillus helveticus have been identified as the active components. These tripeptides function as angiotensin-I-converting enzyme inhibitors and reduce blood pressure. The Japanese company Calpis (Kanagawa, Japan) has developed a pasteurized product based on this technology, Ameal-S, which has functional food status in Japan. Unlike many other probiotic-induced effects, it is important to note that this effect is mediated by a fermentation end product, not viable probiotic cells themselves. [152]

Another antihypertensive activity was associated with cell wall fragments of L. casei YIT9018. [153] In a placebo-controlled trial with 28 human hypertensive subjects, powdered cell extracts (not viable cells) were administered orally and effects on systolic pressure, diastolic pressure, and heart rate were determined. Small, but significant decreases in all three were noted. An interesting characteristic of these activities is that neither requires viable cells, and they provide novel mechanisms for probiotic-mediated effects. Taken together, they suggest that probiotics bacteria may be effective in mediating an antihypertensive effect. [152]

Allergy

Little is known about the efficacy of probiotics in preventing food allergy. [152] It has been suggested that gut flora modulation may downregulate gut inflammation and hypersensitivity that would otherwise lead to atopic eczema. [9] The strongest evidence is for the prevention of atopic dermatitis when certain probiotics are administered to pregnant mothers and newborns up to 6 months of age.

However, a recent clinical trial did not confirm these results. With regard to the treatment of allergic disease, a few well-designed studies have provided evidence that specific probiotic strains can be effective in the treatment of a subset of patients with atopic eczema. [27]

Safety

The safety of a probiotic depends on several factors:

Ability to transfer genetic materialSensitivity to antibioticsAbility to produce hazardous substancesImmune status of the host organismNoninfectious nature

 Future Interventions



With the advanced techniques of molecular biology offers the possibility of genetic screening, which lead to identification of new probiotic strains having multiple beneficial effects in difficult environmental conditions. To create new strains of genetically modified probiotic is essential to know all their possible mechanisms of action. Although genetic modification (GM) of probiotic bacteria can bring significant improvements, formidable barriers were imposed which lead to restrictions for their use commercially [4]Three strains of Propionibacterium freudenreichii previously selected in vitro for their tolerance to acid stress and their ability to produce propionic acid were administered for 20 days to rats colonized by a human microbiota. All three strains showed high survival rates in caecal and faecal contents (up to 3 × 10 8 CFUg/L) as well as transcriptional activity. One strain also increased concentrations of short-chain fatty acids in the caecum. Given these promising features, propioni bacteria must now give proof of their probiotic properties [154] Food matrices as fruits and vegetables offer a promising performance as sources and carriers of probiotic strainsSeveral kinds of signaling molecules are released by the bacteria to interact with other bacteria and components of immunity. These signaling molecules could become a new generation of drugs designed to interfere with virulence and pathogenesis

References

1Metchnikoff E. The Prolongation of Life. Heinemann, London, UK 1907.
2Fuller R. Probiotics in human medicine. Gut 1991;32:439-42.
3Rolfe RD. The role of probiotic cultures in the control of gastrointestinal health. J Nutr 2000;130:2S Suppl:396S-402S.
4Corcionivoschi N, Drinceanu D, Steff L, Luca I, Julean C, Mingyart O. Probiotics-identification and ways of action. Innovative Romanian Food Biotechnol 2010;6:1-11.
5Singh K, Kallali B, Kumar A, Thaker V. Probiotics: A review. Asian Pac J Trop Biomed 2011;S287-90.
6Lilly DM, Stillwell RH. Probiotics: Growth-promoting factors produced by microorganisms. Science 1965;147:747-8.
7Paraschiv D, Vasile A, Constantin M, Ciobanu A, Bahrim G. Study of physiological properties of some probiotics in multiple cultures with mesophilic lactic acid bacteria by Flora Danica Ch. Hansen commercial starter. AUDJG - Food Technol 2011;35:56-65.
8Sanders ME, Guarner F, Mills D, Pot B, Rafter J, Rastall B, et al. Selected topics in probiotics and prebiotics: Meeting report for the 2004 international scientific association for probiotics and prebiotics. Curr Issues Intest Microbiol 2005;6:55-68.
9Gibson GR. Functional foods: Probiotics and prebiotics. Oxoid Culture 2007;28:1-3.
10Fooks LJ, Fuller R, Gibson GR. Prebiotics, probiotics and human gut microbiology. Int Dairy J 1999;9:53-61.
11Crittenden R, Karppinen S, Ojanen S, Tenkanen M, Fagerström R, Mättö J, et al. In vitro fermentation of cereal dietary fibre carbohydrates by probiotic and intestinal bacteria. J Sci Food Agric 2002;82:781-9.
12Gibson GR, Beatty ER, Wang X, Cummings JH. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 1995;108:975-82.
13Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in't Veld JH. Overview of gut flora and probiotics. Int J Food Microbiol 1998;41:85-101.
14Aso Y, Akazan H. Prophylactic effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer. BLP Study Group. Urol Int 1992;49:125-9.
15Spanhaak S, Havenaar R, Schaafsma G. The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans. Eur J Clin Nutr 1998;52:899-907.
16Naidu AS, Bidlack WR, Clemens RA. Probiotic spectra of lactic acid bacteria (LAB). Crit Rev Food Sci Nutr 1999;39:13-126.
17Klein G, Pack A, Bonaparte C, Reuter G. Taxonomy and physiology of probiotic lactic acid bacteria. Int J Food Microbiol 1998;41:103-25.
18Shortt C. Living it up for dinner. Chem Ind 1998;8:300-3.
19Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 1999;116:1107-14.
20Fuller R. Probiotics in man and animals. J Appl Bacteriol 1989;66:365-78.
21Pedrosa MC, Golner BB, Goldin BR, Barakat S, Dallal GE, Russell RM. Survival of yogurt-containing organisms and Lactobacillus gasseri (ADH) and their effect on bacterial enzyme activity in the gastrointestinal tract of healthy and hypochlorhydric elderly subjects. Am J Clin Nutr 1995;61:353-9.
22Schultz M, Munro K, Tannock GW, Melchner I, Göttl C, Schwietz H, et al. Effects of feeding a probiotic preparation (SIM) containing inulin on the severity of colitis and on the composition of the intestinal microflora in HLA-B27 transgenic rats. Clin Diagn Lab Immunol 2004;11:581-7.
23Malin M, Suomalainen H, Saxelin M, Isolauri E. Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab 1996;40:137-45.
24Gupta P, Andrew H, Kirschner BS, Guandalini S. Is Lactobacillus GG helpful in children with Crohn's disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 2000;31:453-7.
25Friedman G, George J. Treatment of refractory pouchitis with probiotic and probiotic therapy. Gastroenterology 2000;118:A4167.
26Marteau P, Pochart P, Flourié B, Pellier P, Santos L, Desjeux JF, et al. Effect of chronic ingestion of a fermented dairy product containing Lactobacillus acidophilus and Bifidobacterium bifidum on metabolic activities of the colonic flora in humans. Am J Clin Nutr 1990;52:685-8.
27Guarner F, Khan AG, Garisch J, Eliakim R, Gangl A, Thomson A, et al. Prebiotics and probiotics. World Gastroenterology Organisation Practice Guideline, 2008.
28Kamada N, Inoue N, Hisamatsu T, Okamoto S, Matsuoka K, Sato T, et al. Nonpathogenic Escherichia coli strain Nissle1917 prevents murine acute and chronic colitis. Inflamm Bowel Dis 2005;11:455-63.
29Kruis W, Schütz E, Fric P, Fixa B, Judmaier G, Stolte M. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 1997;11:853-8.
30Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: A randomised trial. Lancet 1999;354:635-9.
31Kruis W, Fric P, Stolte MS. Maintenance of remission in ulcerative colitis is equally effective with Escherichia coli Nissle 1917 and with standard mesalamine. Gastroenterology 2001;120 Suppl 1:A127.
32Malchow HA. Crohn's disease and Escherichia coli: A new approach in therapy to maintain remission of colonic Crohn's disease? J Clin Gastroenterol 1997;25:653-8.
33Plein K, Holz J. Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea--a pilot study. Z Gastroenterol 1993;31:129-34.
34Guslandi M, Mezzi G, Sorghi M, Testoni PA. Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis Sci 2000;45:1462-4.
35Castex F, Corthier G, Jouvert S, Elmer GW, Lucas F, Bastide M. Prevention of Clostridium difficile induced experimental pseudomembranous colitis by Saccharomyces boulardii: A scanning electron microscopic and microbiological study. J Gen Microbiol 1990;136:1085-9.
36Corcionivoschi N, Drinceanu D. Probioticele-la timpul prezent. Timisoara: Editura Mirton; 2009.
37Brashears MM, Reilly SS, Gilliland SE. Antagonistic action of cells of Lactobacillus lactis toward Escherichia coli O157:H7 on refrigerated raw chicken meat. J Food Prot 1998;61:166-70.
38Forestier C, De Champs C, Vatoux C, Joly B. Probiotic activities of Lactobacillus casei rhamnosus: In vitro adherence to intestinal cells and antimicrobial properties. Res Microbiol 2001;152:167-73.
39Fukushima Y, Kawata Y, Hara H, Terada A, Mitsuoka T. Effect of a probiotic formula on intestinal immunoglobulin a production in healthy children. Int J Food Microbiol 1998;42:39-44.
40Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi H. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain. Pediatr Res 1992;32:141-4.
41Link-Amster H, Rochat F, Saudan KY, Mignot O, Aeschlimann JM. Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. FEMS Immunol Med Microbiol 1994;10:55-63.
42Perdigon G, de Macias ME, Alvarez S, Oliver G, de Ruiz Holgado AA. Effect of perorally administered lactobacilli on macrophage activation in mice. Infect Immun 1986;53:404-10.
43Pouwels PH, Leer RJ, Boersma WJ. The potential of Lactobacillus as a carrier for oral immunization: Development and preliminary characterization of vector systems for targeted delivery of antigens. J Biotechnol 1996;44:183-92.
44Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhea and shedding of rotavirus. Lancet 1994;344:1046-9.
45Takeda K, Suzuki T, Shimada SI, Shida K, Nanno M, Okumura K. Interleukin- 12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota. Clin Exp Immunol 2006;146:109-15.
46Cox JM, Clayton CL, Tomita T, Wallace DM, Robinson PA, Crabtree JE. cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes. Infect Immun 2001;69:6970-80.
47Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol 1999;276:G941-50.
48Miettinen M, Lehtonen A, Julkunen I, Matikainen S. Lactobacilli and Streptococci activate NF-kappa B and STAT signaling pathways in human macrophages. J Immunol 2000;164:3733-40.
49Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 2002;99:15451-5.
50Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869-71.
51Henke JM, Bassler BL. Bacterial social engagements. Trends Cell Biol 2004;14:648-56.
52Johnsborg O, Diep DB, Nes IF. Structural analysis of the peptide pheromone receptor PlnB, a histidine protein kinase from Lactobacillus plantarum. J Bacteriol 2003;185:6913-20.
53Eijsink VG, Axelsson L, Diep DB, Håvarstein LS, Holo H, Nes IF. Production of class II bacteriocins by lactic acid bacteria; an example of biological warfare and communication. Antonie Van Leeuwenhoek 2002;81:639-54.
54Conway PL, Gorbach SL, Goldin BR. Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells. J Dairy Sci 1987;70:1-12.
55Goldin BR, Gorbach SL, Saxelin M, Barakat S, Gualtieri L, Salminen S. Survival of Lactobacillus species (strain GG) in human gastrointestinal tract. Dig Dis Sci 1992;37:121-8.
56Kleeman EG, Klaenhammer TR. Adherence of Lactobacillus species to human fetal intestinal cells. J Dairy Sci 1982;65:2063-9.
57Castagliuolo I, LaMont JT, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 1996;64:5225-32.
58Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999;67:302-7.
59Pothoulakis C, Kelly CP, Joshi MA, Gao N, O'Keane CJ, Castagliuolo I, et al. Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum. Gastroenterology 1993;104:1108-15.
60Tuomola E, Crittenden R, Playne M, Isolauri E, Salminen S. Quality assurance criteria for probiotic bacteria. Am J Clin Nutr 2001;73 Suppl 2:393S-98S.
61Guarner F, Schaafsma GJ. Probiotics. Int J Food Microbiol 1998;39:237-8.
62Brassart D, Schiffrin E, Rochat F, Offord EA, Macé C, Neeser J-R. The future of functional foods: Scientific basis and future requirements. Lebensmittel Technol 1998;7-8:258-66.
63Marteau P, Rambaud JC. Potential of using lactic acid bacteria for therapy and immunomodulation in man. FEMS Microbiol Rev 1993;12:207-20.
64Tannock GW. Probiotic properties of lactic-acid bacteria: Plenty of scope for fundamental R and D. Trends Biotechnol 1997;15:270-4.
65Huis in't Veld J, Shortt C. Selection criteria for probiotic microorganisms. In: Leeds AR, Rowland IR, editors. Gut flora and health: Past, present and future. London: The Royal Society of Medicine Press Ltd; 1996. p. 19-26.
66Collins JK, Thornton G, Sullivan GO. Selection of probiotic strains for human applications. Int Dairy J 1998;8:487-90.
67Salminen S, Isolauri E, Salminen E. Clinical uses of probiotics for stabilizing the gut mucosal barrier: Successful strains and future challenges. Antonie Van Leeuwenhoek 1996;70:347-58.
68Henriksson A, Khaled AK, Conway PL. Lactobacillus colonization of the gastrointestinal tract of mice after removal of the non-secreting stomach region. Microb Ecol Health Dis 1999;11:96-9.
69Lee YK, Salminen S. The coming of age of probiotics. Trends Food Sci Technol 1995;6:241-5.
70Malin M, Verronen P, Korhonen H, Syväoja EL, Salminen S, Mykkänen H, et al. Dietary therapy with Lactobacillus GG, bovine colostrum or bovine immune colostrum in patients with juvenile chronic arthritis: Evaluation of effect on gut defence mechanisms. Inflammopharmacology 1997;5:219-36.
71Salminen S, Laine M, von Wright A, Vuopio-Varkila J, Korhonen T, Mattila-Sandholm T, et al. Clinical uses of probiotics for stabilizing the gut mucosal barrier: Successful strains and future strains to assess their potential in functional foods: A Nordic and European approach. Biosci Microflora 1996;15:61-7.
72Lehto EM, Salminen SJ. Adhesion of twelve different Lactobacillus strains to Caco-2 cell cultures. Nutr Today 1996;31:49-50.
73Lehto EM, Salminen S. Adhesion of two Lactobacillus strains, one Lactococcus strain and one Propionibacterium strain to cultured human intestinal Caco-2 cell line. Biosci Microflora 1997;16:13-7.
74Tuomola EM, Salminen SJ. Adhesion of some probiotic and dairy Lactobacillus strains to Caco-2 cell cultures. Int J Food Microbiol 1998;41:45-51.
75Coconnier MH, Klaenhammer TR, Kernéis S, Bernet MF, Servin AL. Protein-mediated adhesion of Lactobacillus acidophilus BG2FO4 on human enterocyte and mucus-secreting cell lines in culture. Appl Environ Microbiol 1992;58:2034-9.
76Bernet MF, Brassart D, Neeser JR, Servin AL. Adhesion of human bifidobacterial strains to cultured human intestinal epithelial cells and inhibition of enteropathogen-cell interactions. Appl Environ Microbiol 1993;59:4121-8.
77Greene JD, Klaenhammer TR. Factors involved in adherence of lactobacilli to human Caco-2 cells. Appl Environ Microbiol 1994;60:4487-94.
78Crociani J, Grill JP, Huppert M, Ballongue J. Adhesion of different bifidobacteria strains to human enterocyte-like Caco-2 cells and comparison with in vivo study. Lett Appl Microbiol 1995;21:146-8.
79Sarem F, Sarem-Damerdji LO, Nicolas JP. Comparison of the adherence of three Lactobacillus strains to Caco-2 and Int-407 human intestinal cell lines. Lett Appl Microbiol 1996;22:439-42.
80Klaenhammer TR, Kullen MJ. Selection and design probiotics. Int J Food Microbiol 1999;50:45-57.
81Quwehand AC, Vesterlund S, editors. Antimicrobial components from lactic acid bacteria. Lactic acid bacteria microbiological and functional aspects. New York: Marcel Dekker Inc; 2004.
82Cakir I. Determination of some probiotic properties on Lactobacilli and Bifidobacteria. Ankara University Thesis of Ph.D. 2003.
83Ouwehand AC. Antimicrobial components from lactic acid bacteria. In: Salminen S, von Wright A, editors. Lactic acid bacteria: Microbiology and functional aspects, 2 nd ed.. New York: Marcel Dekker Inc; 1998. p. 139-60.
84Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A, Gibson GR, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr 1998;80 Suppl 1:S147-71.
85Clements ML, Levine MM, Ristaino PA, Daya VE, Hughes TP. Exogenous lactobacilli fed to man-their fate and ability to prevent diarrheal disease. Prog Food Nutr Sci 1983;7:29-37.
86Salminen S, Ouwehand A, Benno Y, Lee YK. Probiotics: How should they be defined? Trends Food Sci Technol 1999;10:107-10.
87Szajewska H, Skórka A, Ruszczyñski M, Gieruszczak-Bia³ek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children: Updated analysis of randomised controlled trials. Aliment Pharmacol Ther 2013;38:467-76.
88Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573-81.
89Surawicz CM, McFarland LV, Greenberg RN, Rubin M, Fekety R, Mulligan ME, et al. The search for a better treatment for recurrent Clostridium difficile disease: Use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000;31:1012-7.
90McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 2010;16:2202-22.
91Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterology 1989;96:981-8.
92Isolauri E, Kaila M, Mykkänen H, Ling WH, Salminen S. Oral bacteriotherapy for viral gastroenteritis. Dig Dis Sci 1994;39:2595-600.
93Majamaa H, Isolauri E, Saxelin M, Vesikari T. Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J Pediatr Gastroenterol Nutr 1995;20:333-8.
94Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics 1991;88:90-7.
95Born P, Lersch C, Zimmerhackl B, Classen M. The Saccharomyces boulardii therapy of HIV-associated diarrhea. Dtsch Med Wochenschr 1993;118:765.
96Saint-Marc T, Rossello-Prats L, Touraine JL. Efficacy of Saccharomyces boulardii in the treatment of diarrhea in AIDS. Ann Med Interne (Paris) 1991;142:64-5.
97Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: A systematic review. Am J Gastroenterol 2009;104:1033-49;quiz 1050.
98Liu KX, Zhu YG, Zhang J, Tao LL, Lee JW, Wang XD, et al. Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: A systematic review and meta-analysis. Crit Care 2012;16:R109.
99Aiba Y, Suzuki N, Kabir AM, Takagi A, Koga Y. Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model. Am J Gastroenterol 1998;93:2097-101.
100Kabir AM, Aiba Y, Takagi A, Kamiya S, Miwa T, Koga Y. Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model. Gut 1997;41:49-55.
101Midolo PD, Lambert JR, Hull R, Luo F, Grayson ML. In vitro inhibition of Helicobacter pylori NCTC 11637 by organic acids and lactic acid bacteria. J Appl Bacteriol 1995;79:475-9.
102Loguercio C, Del Vecchio Blanco C, Coltorti M. Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: A controlled study. J Int Med Res 1987;15:335-43.
103Read AE, McCarthy CF, Heaton KW, Laidlaw J. Lactobacillus acidophilus (enpac) in treatment of hepatic encephalopathy. Br Med J 1966;1:1267-9.
104Scevola D, Zambelli A, Concia E, Perversi L, Candiani C. Lactitol and neomycin: Monotherapy or combined therapy in the prevention and treatment of hepatic encephalopathy? Clin Ter 1989;129:105-11.
105Ruseler-Van Embden JG, Hazenberg MP, Van Lieshout LM, Ruud Schouten R. Instability of the pouch flora: Cause of pouchitis? Microecol Ther 1995;23:81-8.
106Gionchetti P, Rizello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000;119:305-9.
107Sheil B, Shanahan F, O'Mahony L. Probiotic effects on inflammatory bowel disease. J Nutr 2007;137 (3 Suppl 2):819S-24S.
108Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr 2009;139:905-11.
109Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003;37:343-50.
110Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol 2008;49:821-30.
111Meyer AL, Elmadfa I, Herbacek I, Micksche M. Probiotic, as well as conventional yogurt, can enhance the stimulated production of proinflammatory cytokines. J Hum Nutr Diet 2007;20:590-8.
112Rizki G, Arnaboldi L, Gabrielli B, Yan J, Lee GS, Ng RK, et al. Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1. J Lipid Res 2006;47:2280-90.
113Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 2005;39:540-3.
114Carr FJ, Chill D, Maida N. The lactic acid bacteria: A literature survey. Crit Rev Microbiol 2002;28:281-370.
115Roselli M, Finamore A, Britti MS, Mengheri E. Probiotic bacteria Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG protect intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenic Escherichia coli K88. Br J Nutr 2006;95:1177-84.
116Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PS, Goulet J, Tompkins TA. Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect Immun 2005;73:5183-8.
117Tallon R, Arias S, Bressollier P, Urdaci MC. Strain- and matrix-dependent adhesion of Lactobacillus plantarum is mediated by proteinaceous bacterial compounds. J Appl Microbiol 2007;102:442-51.
118Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011;CD005496.
119Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: A systematic review of randomised controlled trials. Lancet 2007;369:1614-20.
120Mihatsch WA. Probiotics in preterm. Monatsschr Kinderheilk 2008;156:1070-5.
121Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: A multicenter, randomized, controlled trial. Pediatrics 2008;122:693-700.
122Laparra JM, Sanz Y. Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion. J Cell Biochem 2010;109:801-7.
123Olivares M, Laparra M, Sanz Y. Influence of Bifidobacterium longum CECT 7347 and gliadin peptides on intestinal epithelial cell proteome. J Agric Food Chem 2011;59:7666-71.
124Laparra JM, Olivares M, Gallina O, Sanz Y. Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model. PLoS One 2012;7:e30744.
125Chenoll E, Codoñer FM, Silva A, Ibáñez A, Martinez-Blanch JF, Bollati-Fogolín M, et al. Genomic sequence and pre-clinical safety assessment of Bifidobacterium longum CECT 7347, a probiotic able to reduce the toxicity and inflammatory potential of gliadin-derived peptides. J Prob Health 2013;1:106.
126Narang S, Gupta R, Narang A. Probiotics in oral healthcare-A review. Int J Scientific and Engg Res 2011;2:1-5.
127Riccia DN, Bizzini F, Perilli MG, Polimenni A, Trinchieri V, Amicosante G, et al. Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease. Oral Dis 2007;13:376-85.
128Kõll-Klais P, Mändar R, Leibur E, Marcotte H, Hammarström L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: Species composition and antimicrobial activity. Oral Microbiol Immunol 2005;20:354-61.
129Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds. J Clin Periodontol 2006;33:226-32.
130Weir EI, Peng R, Bian ML, Matharu K, Shu Q. Zyactinase Stimulates the probiotic gut microflora whilst inhibiting pathogenic microflora. Int J Probiotics Prebiotics 2008;3:231-8.
131Tanaka R. Clinical effects of bifidobacteria and lactobacilli. In: Fuller R, Heidt PJ, Rusch V, Waaij DV, editors. Probiotics: Prospects of use in opportunistic infections. Institute for Microbiology and Biochemistry. Herborn-Dill, Germany: 1995. p. 141-56.
132Kumar R, Mukherjee M, Bhandari M, Kumar A, Sidhu H, Mittal RD. Role of Oxalobacter formigenes in calcium oxalate stone disease: A study from North India. Eur Urol 2002;41:318-22.
133Hoppe B, Leumann E, von Unruh G, Laube N, Hesse A. Diagnostic and therapeutic approaches in patients with secondary hyperoxaluria. Front Biosci 2003;8:e437-43.
134Sasikumar P, Gomathi S, Anbazhagan K, Selvam GS. Secretion of biologically active heterologous oxalate decarboxylase (OxdC) in Lactobacillus plantarum WCFS1 using homologous signal peptides. Biomed Res Int 2013;2013:280432.
135Drasar BS, Hill MJ. Intestinal bacteria and cancer. Am J Clin Nutr 1972;25:1399-404.
136Otte JM, Mahjurian-Namari R, Brand S, Werner I, Schmidt WE, Schmitz F. Probiotics regulate the expression of COX-2 in intestinal epithelial cells. Nutr Cancer 2009;61:103-13.
137Bassaganya-Riera J, Viladomiu M, Pedragosa M, De Simone C, Hontecillas R. Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS One 2012;7:e34676.
138Putaala H, Salusjärvi T, Nordström M, Saarinen M, Ouwehand AC, Bech Hansen E, et al. Effect of four probiotic strains and Escherichia coli O157:H7 on tight junction integrity and cyclo-oxygenase expression. Res Microbiol 2008;159:692-98.
139Saito T, Sugimoto N, Ohta K, Shimizu T, Ohtani K, Nakayama Y, et al. Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-κB and MAPK activations and cell proliferation through protein kinase A-or exchange protein activated by cAMP-dependent signal pathway. ScientificWorldJournal 2012;2012:748572.
140Dubey V, Ghosh AR, Mandal BK. Appraisal of conjugated linoleic acid production by probiotic potential of Pediococcus spp. GS4. Appl Biochem Biotechnol 2012;168:1265-76.
141Rowland I. Modification of gut flora metabolism by probiotics and oligosaccharides. In: Fuller R, Heidt PJ, Rusch V, Waaij DV, editors. Probiotics: Prospects of use in Opportunistic Infections. Institute for Microbiology and Biochemistry. Herborn-Dill, Germany:1995. p. 35-44.
142Gilliland SE, Kim HS. Effect of viable starter culture bacteria in yogurt on lactose utilization in humans. J Dairy Sci 1984;67:1-6.
143Kim HS, Gilliland SE. Lactobacillus acidophilus as a dietary adjunct for milk to aid lactose digestion in humans. J Dairy Sci 1983;66:959-66.
144Pettoello Mantovani M, Guandalini S, Ecuba P, Corvino C, di Martino L. Lactose malabsorption in children with symptomatic Giardia lamblia infection: Feasibility of yogurt supplementation. J Pediatr Gastroenterol Nutr 1989;9:295-300.
145Gilliland SE, Nelson CR, Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol 1985;49:377-81.
146Harms HK, Bertele-Harms RM, Bruer-Kleis D. Enzyme-substitution therapy with the yeast Saccharomyces cerevisiae in congenital sucrase-isomaltase deficiency. N Engl J Med 1987;316:1306-9.
147Champié I, Rousseau G. Probiotic formula: To address physical and psychological symptoms of stress. Nutra Foods 2011;10:13-17.
148Takano T. Milk derived peptides and hypertension reduction. Int Dairy J 1998;8:375-81.
149Nakamura Y, Yamamoto N, Sakai K, Takano T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J Dairy Sci 1995;78:1253-7.
150Nakamura Y, Masuda O, Takano T. Decrease of tissue angiotensin I-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci Biotechnol Biochem 1996;60:488-89.
151Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 1996;64:767-71.
152Sanders ME. Considerations for use of probiotic bacteria to modulate human health. J Nutr 2000;130 (2S Suppl):384S-90S.
153Sawada H, Furushiro M, Hirai K, Motoike M, Watanabe T, Yokokura T. Purification and characterization of an antihypertensive compound from Lactobacillus casei. Agric Biol Chem 1990;54:3211-9.
154Lan A, Bruneau A, Philippe C, Rochet V, Rouault A, Hervé C, et al. Survival and metabolic activity of selected strains of Propioni bacterium freudenreichii in the gastrointestinal tract of human microbiota-associated rats. Brit J Nutr 2007;97:714-24.