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Role of probiotics in the modulation of intestinal infections and inflammation.

PURPOSE OF REVIEW: Using microorganisms to influence positively the course of an illness caused by injurious microorganisms is an approach with mounting clinical evidence showing efficacy. Whereas antibiotics will remain an important therapeutic option, there are limitations and problems to their increasing and chronic usage, and probiotics offer a strategy to reduce antibiotic usage. Increasingly, it has become clear that the mechanisms whereby probiotics can impact in intestinal diseases involve a large repertoire of responses. This review summarizes recent findings on how probiotics may effect benefit through interactions with host eukaryotic cells. RECENT FINDINGS: Limiting the access of microbes associated with the development of disease to host mucosal surfaces and altering the responses of host to microbial insults are potential mechanisms whereby probiotics can influence the pathogenesis of disease. Evidence is accumulating that live, viable probiotic organisms diminish accessibility to intestinal epithelial cell; however, the mucosal exclusion is not through direct blockage of shared epithelial receptors between probiotic microbes and pathogenic organisms. Modulation of mucosal defenses such as innate protective mechanisms, enhanced epithelial cell survival, and immune responses have all been shown to have potential in aiding in these actions. Intestinal epithelial cell adherence influences response and, as such, appears to be necessary but may not be wholly sufficient, because soluble bacterial factors have been reported to effect modulation of immune and nonimmune responses of eukaryotic cells. SUMMARY: There is a considerable repertoire of responses potentially responsible for the effects of probiotics, and these responses appear to involve a complex interplay between the microbes of the intestinal tract and the cells of the host. Continued work can be expected to further the understanding of the mechanisms involved, and more work is needed to determine the relative clinical importance of each of the phenomena. These studies are expected to help direct the most efficacious use of probiotics for inflammatory conditions arising from the intestinal tract.

Journal Article↗

Probiotics and prebiotics in gastrointestinal disorders.

PURPOSE OF REVIEW: This review summarizes the clinical efficacy of probiotics and prebiotics in gastrointestinal disorders and examines the mechanisms of action related to their therapeutic effect. RECENT FINDINGS: The demonstration that immune and epithelial cells can discriminate between different microbial species has extended the known mechanism(s) of action of probiotics beyond simple barrier and antimicrobial effects. It has also confirmed that probiotic bacteria modulate mucosal and systemic immune activity and epithelial function. The progressive unraveling of these mechanisms of action has led to new credence for the use of probiotics and prebiotics in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children, recurrent Clostridium difficile-induced infections and postoperative pouchitis. Level II evidence is emerging for the use of probiotics in other gastrointestinal infections, prevention of postoperative bacterial translocation, irritable bowel syndrome, and in both ulcerative colitis and Crohn disease. Nevertheless, one consistent feature has emerged over the past year: Not all probiotic bacteria have similar therapeutic effects. Future clinical trials will need to incorporate this fact into trial planning and design. SUMMARY: The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the "mainstream." Mechanisms of action explain the therapeutic effects and randomized; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium.

Journal Article↗

Genomic Insights Into the Probiotic and Safety Attributes of Pediococcus acidilactici BC-7 for its Potential Application in Livestock Health.

Pediococcus acidilactici is widely recognized for its health-beneficial aspects and has gained increasing interest for use in livestock industry. It shows strong probiotic efficacy, antimicrobial activity, cholesterol-lowering potential, immune modulation, and other therapeutic attributes. The novel strain from indigenous habitats mainly depicted potent probiotic efficacy and high adaptability. In this study, we evaluated the probiotic characteristics and genomic features of strain BC-7 obtained from a Nili - Ravi buffalo calf raised under domestic conditions using phenotypic assessment, genomic analysis and in vivo studies. The strain BC-7 exhibited key probiotic traits i.e., gut tolerance (70.43% - 97.5%), auto-aggregation (85.24%), co-aggregation (14.33% - 25.88%), hydrophobicity (78.33% - 88%), antioxidant potential (54%), and antibacterial activity (16.47-18 mm). The safety analysis revealed that BC-7 exhibited susceptibility and resistance to various antimicrobial agents and showed no β hemolytic activity. BC-7 was taxonomically classified as Pediococcus acidilactici by 16 S rRNA gene sequencing. Whole genome sequence (WGS) analysis showed that P. acidilactici BC-7 contains a 1.9 Mb genome with 42% GC content. Pediococccus acidilactici BC-7 harbored 1900 genes, which were mainly associated with metabolism and genetic processes. Based on genomic comparison, BC-7 shared 99% average nucleotide identity and strong genomic collinearity with P. acidilactici NARCC1 which is a TYPE strain having potent probiotic potential. Probiotic strain BC-7 shared 1,664 core genes with reference strains and 69 unique genes specific for metabolism and genetic processes. The BC-7 strain contained unique bacteriocins-associated genes and defense-related CAzymes, it harbors only vancomycin resistance genes and lacked true virulence determinants. In vivo trial showed that BC-7 treated mice showed increased growth rate, improved immune modulation, and membrane integrity. These significant findings revealed that BC-7 emerging as a potential probiotic strain with strong functionality and efficacy. Thus, our strain BC-7 could be used as a promising candidate for applications in the animal health industry.

Gastrointestinal tract↗

Probiotics in inflammatory bowel disease--therapeutic rationale and role.

The intestinal flora has a conditioning effect on intestinal homeostasis, delivering regulatory signals to the epithelium, the mucosal immune system and to the neuromuscular activity of the gut. Beneficial metabolic activities of the enteric flora include nutrient production, metabolism of dietary carcinogens, conversion of prodrugs to active drugs. However, increasing evidence suggests that some components of the enteric flora are essential ingredients in the pathogenesis of inflammatory bowel disease (IBD); this has prompted interest in therapeutic manipulation of the flora with probiotics. Probiotics are biologic control agents-described as live microbial food supplements which confer a health benefit beyond inherent basic nutrition. Multiple potential beneficial effects have been attributed to the probiotic use of lactic acid bacteria, bifidobacteria and other non-pathogenic commensals. At present, much of the promise of probiotics remains outside the realm of evidence-based medicine and awaits the results of prospective trials, now underway. No reliable in vitro predictors of in vivo efficacy of putative probiotics have been identified. Rigorous comparisons of probiotic performance have not been performed and the suitability of a given probiotic for different individuals is largely unexplored. Notwithstanding, an improved understanding of the normal commensal flora and host-flora interactions has the potential to open up new therapeutic strategies for inflammatory disorders of the gut.

Animals↗

Induction of local protective immunity to Eimeria acervulina by a Lactobacillus-based probiotic.

Previously we have shown that resistance to Eimeria acervulina (EA) infection in broiler chickens was enhanced by a probiotic treatment. In the present studies, we examined cytokine and oocyst production under similar conditions using a commercial Lactobacillus-based probiotic. Day-old male broiler chicks were fed control or probiotic diets and were orally challenged with either 2x10(4) (Experiment 1) or 1x10(4) (Experiment 2) oocysts of EA at 3 weeks of age. For the first experiment, fecal oocyst shedding and IFN-gamma levels in the culture supernatants of ConA-stimulated spleen lymphocytes were evaluated. Humoral and local cell-mediated immunity in the second experiment were assessed by evaluating antibody and cytokine (IFN-gamma and IL-2) levels in sera and intestinal secretions on a 3-day interval post inoculation. Results showed small but significant (P<0.05) differences in cytokine levels and oocyst production but not antibody levels between the probiotic-treated and control groups. Collectively, these data suggest a positive impact of the probiotic on cellular immune responses of infected broilers as compared to control chickens resulting in enhanced resistance to EA as shown in reduced fecal oocyst shedding. The results showed an immunoregulatory effect of probiotic diets on the local cell-mediated immunity in poultry and provide a rationale for further study to investigate the beneficial effects of Lactobacillus-based probiotics in food animals.

Animals↗

The probiotic approach: an alternative treatment option in urology.

OBJECTIVE: The prophylactic and therapeutic use of probiotic microorganisms is a wide and still controversial field. The review paper is aimed to summarize recent findings on the health-benefiting effects of probiotics in urological diseases. The use of certain beneficial strains against urogenital infections, bladder cancer recurrence and renal stone formation is discussed. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Various clinical trials have now been performed which substantiate the beneficial effects of the probiotic strains L. rhamnosus GR-1, L. fermentum RC-14 and L. crispatus CTV-05 against urogenital infections, such as urinary tract infections and bacterial vaginosis. The potential of L. casei Shirota to reduce the recurrence rate of bladder cancer is one of the most intriguing examples for the use of probiotics in medical practice. The use of O. formigenes in the prevention of calcium oxalate stone disease was only recently suggested and needs to be further investigated. CONCLUSION: Clinical trials increasingly provide a profound scientific basis for the use of probiotics in medicinal practice including urology. Efforts to make probiotic products available which are validated according to the guidelines recommended by the WHO and FAO and produced according to Good Manufacturing Practice will contribute to the acceptance of probiotic therapy by both the physicians and the patients.

Animals↗

Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy.

In order to reduce ammonia production by urease-positive bacteria Solga recently hypothesised (S.F. Solga, Probiotics can treat hepatic encephalopathy, Medical Hypotheses 2003; 61: 307-13), that probiotics are new therapeutics for hepatic encephalopathy (HE), and that they may replace antibiotics and lactulose. This influenced our view of the effect of antibiotics, prebiotics, e.g., lactulose, and probiotics on intestinal bacteria in the treatment of HE. Intestinal ammonia arises from aminoacids after bacterial de-amination and not from urea making urease-positive bacteria irrelevant. Antibiotics are not preferred in the treatment of HE, since ammonia-producing antibiotic-resistant bacteria may survive and replace ammonia-producing antibiotic-susceptible bacteria. Intestinal prebiotics are carbohydrate-like compounds, such as lactulose and resistant starch, that beneficially affects host's health in a different manner than normal food. In the small bowel prebiotics are not absorbed and digested, but are fermented in the colon by colonic bacteria. Fermentation of prebiotics yields lactic, acetic and butyric acids, as well as gas especially hydrogen (H2). The massive H2 volumes cause rapid intestinal hurry and thus massive amounts of colonic bacteria, not only urease-positive bacteria, but also deaminating bacteria, are removed and intestinal uptake of toxic bacterial metabolites, e.g., ammonia, reduced. As living non-pathogenic micro-organisms, probiotics beneficially affect the host's health by fermenting non-absorbed sugars, especially in the small bowel. Thus, they reduce the substrate of the other bacteria, and simultaneously they create a surplus of fermentation products which may affect the non-probiotic flora. Regarding the fermentation products (lactic acid, ethanol, acetic acid and CO2) five groups of probiotic micro-organisms are known. It is argued that probiotic, CO2-producing (facultatively) heterolactic lactobacilli, i.e., lactobacilli, that produce both lactic acid and CO2 from sugars, such as glucose, are preferred in the treatment of HE. Our ideas concur with the practice guidelines regarding HE as formulated by Blei, Cordoba and the Practice Parameters Committee of the American College of Gastroenterology, and does not alter the final conclusion of Solga as regards the beneficial use in future treatment of HE.

Ammonia↗

Influence of a probiotic Enterococcus faecium strain on development of the immune system of sows and piglets.

The influence of the probiotic bacterium Enterococcus faecium SF68 on the immune system and the intestinal colonization of pigs were determined in a feeding experiment with sows and piglets. Mucosal immunity of the developing piglets was monitored by isolation and detection of intestinal lymphocyte cell populations from the proximal jejunal epithelium and the continuous Peyers patches by the use of flow cytometry. The levels of intestinal IgA in both groups of piglets were compared, as well as total IgG in the serum of sows and piglets. Feces of the sows and intestinal contents of the piglets were taken for determination of total anaerobe and coliform bacterial counts in both probiotic and control groups. Villus length and depth of the crypts were measured in the jejunum of sacrificed piglets to monitor the development of the intestinal mucosal surface amplification. Total serum IgG of the sows appeared to be unaffected. Piglets of both groups showed similar IgG levels up to 5 weeks after birth with a slight tendency toward lower values in the probiotic group. At an age of 8 weeks the total IgG levels of the probiotic animals were significantly lower (p<0.01). No differences were observed in the populations of CD4+ and CD8+ T cells in the Peyers patches. However, the levels of cytotoxic T cells (CD8+) in the jejunal epithelium of piglets of the probiotic group were significantly reduced. The depth of the jejunal crypts and length of the villi were similar in both groups, suggesting the relative T-cell population differences were not due to alterations in the epithelial cell numbers. The total anaerobe and coliform bacterial populations were not significantly affected by the probiotic treatment, either in sows or in the piglets. However, a remarkable decline in the frequency of beta-haemolytic and O141 serovars of Escherichia coli was observed in the intestinal contents of probiotic piglets, suggesting an explanation for the reduction in cytotoxic T-cell populations.

Animals↗

Production performance, serum/yolk cholesterol and immune competence of white leghorn layers as influenced by dietary supplementation with probiotic.

An experiment was conducted to measure the influence of a dietary probiotic on the production performance, the concentrations of cholesterol in the serum and yolk and immune competence in White Leghorn layers from 25 to 72 weeks of age. One hundred and twenty commercial White Leghorn layers, aged 24 weeks, with an average of 62% hen-day egg production, were equally and randomly distributed into three groups, with eight replicates of 5 birds in each. The birds were reared in individual laying cages. They were placed on one of three dietary treatments: basal, or basal with probiotic supplementation at a rate of 100 or 200 mg/kg feed. The addition of probiotic significantly increased the egg production, shell weight, shell thickness and serum calcium, and reduced the concentrations of cholesterol in the serum and yolk. However, no differences in these traits was observed between the groups receiving 100 or 200 mg probiotic. Feed conversion, egg weight, serum phosphorus and serum alkaline phosphatase activity were not influenced by supplementation with probiotic. Antibody production in response to the inoculation of sheep red blood cells and the cutaneous basophilic hypersensitivity (CBH) responses to inoculation with phytohaemagglutinin did not differ significantly among the dietary groups at either 24 or 40 weeks of age. The antibody titre was significantly higher in the groups supplemented with probiotic at 64 weeks of age. The addition of 100 mg/kg of probiotic in the diet significantly increased the CBH response at 64 weeks of age.

Alkaline Phosphatase↗

Modulating immune responses with probiotic bacteria.

For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria.

Administration, Oral↗

Probiotics in infective diarrhoea and inflammatory bowel diseases.

Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.

Bifidobacterium↗

Specific enumeration of the probiotic strain Enterococcus faecium NCIMB 10415 in the intestinal tract and in faeces of piglets and sows.

The intestinal bacterium Enterococcus faecium NCIMB 10415 (E. faecium SF68) has been used for more than a decade as a probiotic strain in animal nutrition as well as in the prevention and treatment of diarrhoea in humans. Beneficial effects have been shown in feeding and clinical trials. However, the strain has no selective growth markers and monitoring in the intestinal tract is impossible by cultivation. Using specific nucleotide sequences, in this study a probe for colony hybridization was constructed in order to quantify this probiotic strain in feed and intestinal and faecal samples from piglets and sows. The probiotic strain showed almost constant amounts in sow faeces (1.8 x 10(5) cfu/g wet weight), while contents in digesta and piglet faeces varied on a lower level depending on gut section and piglet age. The ratio of specific probiotic counts and total enterococci was much lower than in sow faeces however the strain could be detected reliably in faeces already on the 14th day of life. The application of the colony hybridization method enables for the first time the selective detection of the widely used probiotic E. faecium NCIMB 10415 strain among total Enterococcus spp. counts of digesta, faeces and feed. It is now possible to monitor the presence of the probiotic in the intestinal tract and faeces. Results of this study have implications for the proposed modes of action of probiotics in animal nutrition.

Age Factors↗

Effects of Enterococcus faecium NCIMB 10415 as probiotic supplement on intestinal transport and barrier function of piglets.

Many studies report positive effects of probiotic supplementation on the performance and health of piglets. The intention of this study was to describe the effects of Enterococcus faecium NCIMB 10415 on the transport and barrier functions of pig small intestine to improve our understanding of the underlying mechanisms of this probiotic. Ussing chamber studies were conducted with isolated jejunal epithelia of piglets at the age of 14, 28, 35 and 56 days. Jejunal tissues of the control group were compared with epithelia of piglets that had received a diet supplemented with the probiotic Enterococcus faecium NCIMB 10415. Transport properties (absorption and secretion) of the epithelia were examined by mucosal addition of glucose or L-glutamine or by serosal addition of PGE2. Electrophysiology of the epithelia was continuously recorded and the change in short circuit current (Isc) was determined. Paracellular permeability was measured by measuring the flux rates of mannitol. The increase of Isc caused by mucosal addition of glucose was, at all glucose concentrations, higher in the probiotic group compared with the control group. However, the difference (up to 100% of the control) was not significant. The increase of Isc after the mucosal addition of L-glutamine (12mmol/l) was higher in the tissues of the probiotic group but did not reach significance. Serosal PGE2 induced a significantly higher increase of Isc in tissues of the probiotic group at the age of 28 days. No consistent differences were observed in mannitol transport rates between the feeding groups. Significant age-dependent alterations of absorptive and secretory properties of the jejunal epithelium were observed; these were independent of the treatment. A probiotic supplementation seems to influence transport properties of small intestine epithelium. The increased absorption of glucose could be interpreted as a positive effect for the animal.

Age Factors↗

Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics.

BACKGROUND: Citrobacter rodentium is a naturally occurring murine pathogen that causes colonic epithelial-cell hyperplasia, disrupts the colonic mucosa, and elicits a predominantly T helper 1 cellular immune response; it thereby serves as a model for the study of mechanisms of disease induced by human attaching-effacing pathogens. We sought to determine whether pretreatment of mice with a mixture of Lactobacillus rhamnosus and L. acidophilus probiotics would attenuate C. rodentium-induced colonic disease in mice. METHODS: Mice were administered sterile drinking water, probiotics (10(9) cfu/mL) in sterile drinking water, maltodextrin in sterile drinking water, orogastric C. rodentium (10(7) cfu in 0.1 mL), or maltodextrin in sterile drinking water for 1 week before C. rodentium infection, or they were pretreated with probiotics (10(9) cfu/mL) for 1 week before challenge with C. rodentium. RESULTS: Mice that received viable probiotics remained healthy. C. rodentium infection elicited mucosal inflammation, epithelial-cell hyperplasia, apoptosis in the colon, and interferon (IFN)- gamma production by splenocytes. Pretreatment with probiotics decreased levels of all but IFN- gamma production. CONCLUSIONS: Pretreatment with probiotics attenuates the effects of C. rodentium infection in mice. Understanding the mechanism of these beneficial effects will aid in determining the efficacy of probiotics in preventing infection with related attaching-effacing enteric pathogens in humans.

Animals↗

Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998.

We reviewed the evidence from human intervention studies for the health effects of probiotic bacteria, ie, live bacteria that survive passage through the gastrointestinal tract and have beneficial effects on the host. Of the 49 studies reviewed, 26 dealt with the prevention or treatment of diarrheal disease, 9 with the prevention of cancer or of the formation of carcinogens, 7 with the lowering of serum cholesterol, and 7 with the stimulation of the immune system. The most widely studied probiotic bacteria were Lactobacillus GG (22 studies), Lactobacillus acidophilus (16 studies), Bifidobacterium bifidum (6 studies), and Enterococcus faecium (7 studies). Intake of Lactobacillus GG consistently shortened the diarrheal phase of rotavirus infection by 1 d. However, evidence for the prevention by Lactobacillus GG and other probiotics of diarrhea due to viral or bacterial infections was less strong. Effects of probiotics on the immune system are inconclusive because of the variety of outcome variables reported. Cholesterol lowering by L. acidophilus was shown in some but not all studies; cholesterol lowering by E. faecium seems to be transient. Two studies of one research group showed a smaller recurrence of bladder tumors in patients after treatment with Lactobacillus casei; these results await confirmation. The production of mutagens after a meal might be reduced by the concomitant intake of probiotics, but the relevance of this finding is unclear. In conclusion, consumption of foods containing Lactobacillus GG may shorten the course of rotavirus infection. Other health effects of probiotic bacteria have not been well established. Well-designed placebo-controlled studies with validated outcome variables are needed to determine the health effects of probiotics.

Bifidobacterium↗

Taxonomy and important features of probiotic microorganisms in food and nutrition.

Lactic acid bacteria are among the most important probiotic microorganisms typically associated with the human gastrointestinal tract. Traditionally, lactic acid bacteria have been classified on the basis of phenotypic properties, eg, morphology, mode of glucose fermentation, growth at different temperatures, lactic acid configuration, and fermentation of various carbohydrates. Studies based on comparative 16S ribosomal RNA sequencing analysis, however, showed that some taxa generated on the basis of phenotypic features do not correspond with the suggested phylogenetic relations. Thus, some species are not readily distinguishable by phenotypic characteristics. This is especially true for the so-called Lactobacillus acidophilus group, the Lactobacillus casei and Lactobacillus paracasei group, and some bifidobacteria, strains of which have been introduced in many probiotic foods, eg, the novel yogurt-like commodities. Consequently, modern molecular techniques, including polymerase chain reaction-based and other genotyping methods, have become increasingly important for species identification or for the differentiation of probiotic strains. Probiotic strains are selected for potential application on the basis of particular physiologic and functional properties, some of which may be determined in vitro. The classification and identification of a probiotic strain may give a strong indication of its typical habitat and origin. The species, or even genus name, may also indicate the strain's safety and technical applicability for use in probiotic products. Molecular typing methods such as pulsed-field gel electrophoresis, repetitive polymerase chain reaction, and restriction fragment length polymorphism are extremely valuable for specific characterization and detection of such strains selected for application as probiotics.

Bifidobacterium↗

Probiotics: effects on immunity.

The gastrointestinal tract functions as a barrier against antigens from microorganisms and food. The generation of immunophysiologic regulation in the gut depends on the establishment of indigenous microflora. This has led to the introduction of novel therapeutic interventions based on the consumption of cultures of beneficial live microorganisms that act as probiotics. Among the possible mechanisms of probiotic therapy is promotion of a nonimmunologic gut defense barrier, which includes the normalization of increased intestinal permeability and altered gut microecology. Another possible mechanism of probiotic therapy is improvement of the intestine's immunologic barrier, particularly through intestinal immunoglobulin A responses and alleviation of intestinal inflammatory responses, which produce a gut-stabilizing effect. Many probiotic effects are mediated through immune regulation, particularly through balance control of proinflammatory and anti-inflammatory cytokines. These data show that probiotics can be used as innovative tools to alleviate intestinal inflammation, normalize gut mucosal dysfunction, and down-regulate hypersensitivity reactions. More recent data show that differences exist in the immunomodulatory effects of candidate probiotic bacteria. Moreover, distinct regulatory effects have been detected in healthy subjects and in patients with inflammatory diseases. These results suggest that specific immunomodulatory properties of probiotic bacteria should be characterized when developing clinical applications for extended target populations.

Adjuvants, Immunologic↗

Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women.

Numerous studies report that soy lowers cholesterol. Probiotic bacteria were also reported to lower total cholesterol (TC) and LDL cholesterol (LDL-C). We hypothesized that by altering intestinal microflora, probiotic consumption may also change phytoestrogen metabolism and enhance the effects of soy. To evaluate the independent and interactive effects of probiotic bacteria and soy on plasma TC, LDL-C, HDL cholesterol (HDL-C), and triglycerides (TG), 37 women with a baseline TC of 5.24 mmol/L were given the following 4 treatments for 6 wk each in a randomized crossover design: soy protein isolate (26 +/- 5 g soy protein containing 44 +/- 8 mg isoflavones/d); soy protein isolate + probiotic capsules (10(9) colony-forming units Lactobacillus acidophilus DDS-1 and Bifidobacterium longum); milk protein isolate (26 +/- 5 g milk protein/d); and milk protein isolate + probiotic. Soy consumption decreased plasma TC by 2.2% (P = 0.02) and LDL-C by 3.5% (P = 0.005), increased HDL-C by 4.2% (P = 0.006) and tended to decrease TG (P = 0.07) compared with milk protein intake. When divided according to initial TC concentration, soy effects were observed only in hypercholesterolemic women (TC > 5.17 mmol/L). In this subgroup, soy treatments decreased plasma TC by 3.3% (P = 0.01), LDL-C by 4.5% (P = 0.004), and TG by 10.6% (P = 0.02), and increased HDL-C by 4.2% (P = 0.02). When subjects were divided on the basis of plasma and urine concentrations of the isoflavone metabolite, equol, equol producers and nonproducers did not differ in baseline lipids or in the effects of soy. Probiotics did not lower cholesterol or enhance the effects of soy. These results confirm a beneficial effect of soy on plasma cholesterol in mildly hypercholesterolemic postmenopausal women independent of equol production status, but do not support an independent or additive effect of these particular probiotic bacteria.

Cross-Over Studies↗