You are hereA REVIEW ASPECTS ON PROBIOTIC AND PREBIOTIC A SYNERGESTIC COMBINATION

A REVIEW ASPECTS ON PROBIOTIC AND PREBIOTIC A SYNERGESTIC COMBINATION


CLINICAL APPLICATION OF PROBIOTICS AND PREBIOTICS

5.1. In Gastro Intestinal conditions:-

5.1.1 Diarrhoeasof various origins
5.1.1 Diarrhoeas of various origins
a.    Antibiotic associated diarrhoea
b.    Clostridium difficile diarrhoea
c.    Gastroenteritis
d.    Rotavirus diarrhoea
e.     Paediatric diarrhoea
f.    Lactose intolerance
• Inflammatory bowel disease
a.    Ulcerative Colitis
b.   Crohns disease

• Antibiotic-associated diarrhoea
Diarrhoea is one of the most common side effects of antibiotic therapy. Around 20% of patients on antibiotics experience diarrhoea. Diarrhoea occurs in about 5% to 10% of patients who are treated with ampicillin, 10% to 25% of those who are treated with co-amoxiclav and 2% to 5% of those who are treated with other drugs.6,9,10

Studies have shown that probiotics having strains of Lactobacillus and Bifidobacterium among others had beneficial effects in the prevention of antibiotic-associated diarrhoea. Probiotics are believed to restore the equilibrium in the altered gastrointestinal micro flora, thus protecting against the colonization by pathogens. Several possible mechanisms have been proposed to explain how probiotics work which include stimulation of the immune system, inhibition of epithelial and mucosal adherence of the pathogen, enzymatically modifying toxin receptors, production of antimicrobial substances, competition for nutrients, stimulation of immunoglobulin A and trophic effects on intestinal mucosa.6,9,10

In the recent past, two meta-analyses have been published that evaluated randomized, double masked, controlled trails of probiotics in the prevention of antibiotic associated diarrhoea. These meta analyses confirm the benefit of probiotic treatment over placebo in preventing diarrhoea associated with antibiotics.6, 9, 10

• Clostridium difficile diarrhoea
Antibiotics are known to cause different side effects including damage to the endogenous intestinal flora, which promotes infection, by Clostridium difficile, a pathogenic agent responsible for serious intestinal disorders. Probiotics that have been proposed for prophylaxis and treatment of C.difficile diarrhoea include various bacteria (Bifidobacterium, Lactobacillus, Enterococcus) and yeasts (Saccharomyces).

A clinical study, conducted double blind and placebo controlled, analyzed that effect of the joint administration of probiotics and antibiotics on 138 elderly hospitalized patients. During a 20-day treatment with antibiotics, the patients received a daily capsule of either L. acidophilus and B. bifidum, or a placebo. The parameters observed were the frequency of the diarrhoea attacks and the presence of C. difficile and its toxins in the faeces. Results showed that the number of patients affected by   C. difficile was comparable in the control and test groups. However, it was observed that of all the patients that suffered from diarrhoea, the proportion that had the C. difficile toxin was significantly lower in the group receiving probiotics (2.9% vs. 7.25%) than in the group receiving the placebo. Similarly, the number of patients in whom the toxin was found was smaller in the group receiving the probiotics (46% vs. 78%) compared to the control group. These results are suggestive that the consumption of L. acidophilus and B. difidum probiotics at the same time as treatment with antibiotics prevents the appearance of C. difficile related diarrhoea in the elderly. The emphasis is on the economic stake with C. difficile, which can be reduced by 50% with probiotic use.6,9,10

• Gastroenteritis
Gastroenteritis due to several viral or bacterial pathogens or to parasites is the main cause of acute diarrhoea. Probiotics may help to eradicate pathogens causing gastroenteritis. Several studies suggested a beneficial role of lactic acid bacilli against organisms causing gastroenteritis. The use of probiotics has been implicated for both the curative and the preventive cause. Mechanisms of action implicated include the production of acids, hydrogen peroxide, or antimicrobial substance like bactericocin; competition for nutrients or adhesion receptors; antitoxin actions; and stimulation of the immune system.6, 9, 10, 13

• Rotavirus diarrhoea
There is evidence of the role of probiotics in shortening the duration of diarrhoea in children, and in the prevention of recurrence of diarrhoea. The highest level of evidence is seen in the treatment of acute infectious diarrhoea. Well-controlled trials have shown that probiotics like Lactobacilli can shorten the duration of acute rotavirus diarrhoea. The review by lsolaurie outlines the role of probiotics as therapy and the review by Solis et al reviews the role of probiotics in limiting malnutrition associated with diarrhoea.6, 9, 10, 13

In a meta-analysis of 18 probiotic therapy clinical trials involving children younger than 5 years of age with acute-onset diarrhoea, Huang et al demonstrated that co-administration of probiotics with standard rehydration therapy reduced the duration of diarrhoea by approximalely 24 hours. This metaanalysis was further supported by recent additional randomized placebo controlled studies demonstrating the effect of probiotics on infant diarrhoea. Rosenfeldt et al described the effect of L. rhamnosus and L. reuteri administered twice daily for 5 days to a cohort of children with acute diarrhoea in local day care centers. In children treated with the 2 Lactobacillus strains, the mean duration of diarrhoea was reduced by 40 hours. This same group of scientists studied the same lactobacillus preparation in another 69 hospitalized children with the same dose. The duration of diarrhoea was reduced by 19 hours and the length of hospitalization by 48 in the children receiving probiotics. These two studies confirm that both inpatients and outpatients with primarily rotavirus-induced diarrhoea can be successfully treated with probiotic preparations.6, 9, 10, 13

• Pediatrics diarrhoea
There is adequate evidence that administration of probiotics are effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea.6, 9, 10, 13

Lactobacilliin the intestines play an important role in developing natural defenses against both intestinal bacterial and viral infections. So a prospective clinical study was carried out at Cathay General Hospital to determine the effect of L. acidophlus and B. infantis on the course of acute diarrhoea in hospitalised children. Altogether 100 children between 6 and 60 months of age were collected and randomly allocated into 2 groups. Study group (n = 50) was given L. acidophilus and B. infantis, for 4 days and control group (n = 50) received parenteral rehydration only without any medication. Only 20 stool cultures in study group had positive culture results for Lactobacillus or Bifidobacterium. All children were evaluated for the degree of dehydration before rehydration. The clinical course of diarrhoea was followed during the treatment period. There was no difference between the study group and control group in the frequency of diarrhoea stools on the day before admission. However, the frequency of diarrhoea for study group improved on the first and second day of hospitalization with statistical difference. The duration of diarrhoea during hospitalization in study group also decreased. Oral bacterial therapy is an effective adjuvant therapy in rotavirus positive and negative children with diarrhoea and can safely be administered during an episode of acute diarrhoea.6, 9, 10, 13

• Lactose intolerance
Thousands of people suffer from the congenital deficiency of β-glycosidase, resulting in an inability to digest and absorb lactose. Lactase positive strains of bacteria (e.g., Lactobacillus and Bifidobacterium) are commonly added to pasteurize dairy products to increase digestibility of the lactose present in the dairy product. At adequate daily feeding levels, L. acidophilus may facilitate lactose digestion in lactose-intolerant subjects. Possible mechanisms for the improved lactose digestion by probiotics include:

·         The laclase activity of the bacteria actually does the work of digesting lactose in the product once it reaches the intestine.

·         The slower transit time of yoghurt may permit more time for the residual intestinal lactase and the probiotic strains in yoghurt to digest the lactose.

Levri KM et al, assessed the efficacy of oral probiotics in adults with lactose intolerance through a systematic review of its effects on symptoms and breath hydrogen tests, and whether adding probiotics to non fermented dairy products decreases lactose intolerance at that meal. Evidence from this study suggested that specific strains, concentrations, and preparations were effective in alleviating the symptoms and signs of lactose intolerance in adults.6, 9, 10, 13

Irritable bowel syndrome can remit spontaneously implying that cure is possible. Predictors of good prognosis include a short history, acute onset (possibly post infective origin), absence of psychological disorders, and resolution of chronic life stressors- possible-disease modifying treatments with long-lasting effects include diet and anti-inflammatory and psychological treatments. Research shows that probiotics may have benefit in altering bacterial flora and act as anti-inflammatory agents.6,9,13

O' Mahony et al, conducted a study with the aim to compare the response of symptoms and cytokine ratios in irritable bowel syndrome with ingestion of probiotic preparations containing a Lactobacillus or Bifidobacterium strain Seventy-seven subjects with irritable bowel syndrome were randomised to receive either L. salivarius or B. infantis, in a malted milk drink, or the malted milk drink alone as placebo for g weeks. The cardinal symptoms of IBS were recorded on a daily basis and assessed each week. Quality of life assessment, stool microbiologic studies, and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase. It was observed that those randomized to B- infantis experienced a greater reduction in symptom scores; composite and individual scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty were significantly lower than for placebo for those randomized to B- infantis for most weeks of the treatment phase. At baseline, patients with irritable bowel syndrome demonstrated an abnormal IL-10/IL-12 ratio, indicative of a proinflammatory, Th-1 state, which was normalized by B. infantis feeding alone. It was concluded that B. infantis  elleviates symptoms in irritable bowel syndrome.6,9,13

Halpem et al, conducted a randomized double blind crossover trial using an antidiarrhoeal drug containing L. acidophilus or a placebo. They demonstrated a statistically significant difference in overall G.l function, defined by clinical criteria, in the Lactobacillus group in comparison to those receiving placebo. The abnormalities seen in colonic flora of irritable bowel syndrome suggest that a probiotic approach is justified.6,9,11,13

5.1.2 Inflammatory bowel disease
Probiotics find use in both types of inflammatory bowel disease: ulcertative colilis and Crohn's disease.

• Ulcerative Colitis
Ulcerative colitis is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with ulcerative colitis. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state.
A synbiotic was developed for use in ulcerative colitis patients combining a probiotic, B- longum, isolated from healthy rectal epithelium, and a prebiotic substrate for promotion of growth of the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active ulcerative colitis for a period of one month- Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured. Sigmoidoscopy scores (scale 0-6) were reduced in the test group [start 4.5 (1.4), end 3.1 (2.5)] compared with placebo [start 2.6 (2.1), end 3.2 (2.)]. mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active ulcerative colitis, were significantly reduced in the test group after treatment. Tumour necrosis factor alpha and interleukin 1 alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment. Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue. Short-term symbiotic treatment of active ulcerative colitis resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.6,9,11

• Crohn’s disease
It has been widely speculated that Crohn’s disease has a bacterial origin. A number of bacteria have been implicated but none have been definitively proven to be the culprit. In fact, there is a school of thought that Crohn’s disease may have multiple bacterial origins. Adherent-invasive E. coli has been long thought to be at least one cause of inflammatory bowel diseases including Crohn’s disease. Investigators in France recently demonstrated that certain species of lactobacillus inhibit the attachment of this type of E. coli to epithelial cells6,9,11

5.2. Non Gastro Intestinal applications:-

  a. Probiotics for surgical infections

  b. Women reproductive and bladder health

  c. Cancer

  d. Mucosal immunity

  e. Allergy

a) Probiotics  for surgical infections:
Legend has it that fermented milks were used to help the healing of wounds and to fight infection before antiseptics and antibiotics were available. Nevertheless, the application of viable lactic acid bacteria to an infected wound would represent a paradigm shift in current surgical practice. In a series of animal studies, L. fermentum RC-14 and proteins produced by this organisms were shown to prevent severe Staphyoloccus aureus surgical implant infection Although this does not prove human efficacy, the concept illustrates a different approach to wound infection management. Given the emergence of vancomycin-resistant strains of multidrug-resistant S. aureus, which cause major clinical problems within hospital settings, the application of probiotics or protein-derived products to wounds is worthy of further investigation.5

Application of probiotics for surgical patients is not necessarily limited to skin and wounds. In the first of three intriguing studies, L. plantarum  given with enteral fiber nutrition decreased the rate of postoperative infections in liver transplant patients at very high risk of infection, organ rejection, and death .These patients are immunosuppressed and malnourished, and the infecting organisms often originate in the patient's own intestine, spreading through translocation. Endotoxemia from gut pathogen overgrowth also leads to further complications. The lactobacilli in that study were administered 24 h after surgery four times a day for 6 weeks. Only 13% of patients developed infections, compared to 34 to 48% in controls, with a drop in enterococcal infections being notable. Interestingly, the drop in infections occurred for pneumonia, sepsis, and cholangitis as well as others. In a second paper by Rayes et al. patients undergoing major abdominal surgery (such as resection of the liver, stomach, or pancreas) benefited from L. plantarum 299 in terms of fewer infections, fewer antibiotics prescribed, shorter hospital stay, and lower incidence of other complications. In the third randomized, double-blind study, patients with severe acute pancreatitis who received freeze-dried lactobacilli with oat fiber for 1 week had significantly fewer episodes (4.5% versus 30%) of infection and pancreatic abscesses5

Rather than use antibiotics in an attempt to decontaminate the intestine prior to surgery, these studies indicate that there is merit to administering probiotic organisms to reduce the risk of complications. Further studies are needed on other probiotic strains with different food additives and to determine whether some patients should not be given this therapy because of elevated risk of Lactobacillus-associated bacteremia.5

b) Womens reproductive and bladder health
Although research on probiotics for the female urogenital tract has been ongoing for over 20 years, only recently has others recognized that probiotic applications go beyond consumption of foods. Evidence from a 64-patient randomized, placebo-controlled trial indicates that daily oral intake of 109 to 1010 L. rhamnosus GR-1 and L. fermentum RC-14 leads to transfer of the organisms from the rectum to the vagina as well as an overall depletion of coliforms and yeasts in the vagina . In these studies of over 100 reportedly healthy women, a significant number presented with an abnormal vaginal microbiota indicative of bacterial vaginosis. This agrees with the findings of others and shows clearly that the vaginal microbiota is often abnormal during the menstrual cycle and postmenopause even when the subject is asymptomatic.5,13

Questions have been raised as to how abnormal is defined, given that subjects are not ill. The vaginal micro biota is often in a state of flux, as shown by Nugent score analysis, culture, and molecular tracking.The Nugent score is determined by microscopic analysis of vaginal cells collected from the vagina. When the field of view is dominated by lactobacillus morphotypes, the score is low (0 to 3), and when it is dominated solely by gram-negative rods (indicative of anaerobes like Gardnerella vaginalis or uropathogens like Escherichia coli) or gram-positive cocci like groupB streptococci or enterococci, the score is high (8 to 10). Intermediate values indicate the presence of pathogens and lactobacilli in a sort of transition state. The factors that contribute to the transition from asymptomatic to symptomatic infection or a return to one that is healthy remain to be determined.5,13

Nevertheless, the incidence of urinary tract infection, bacterial vaginosis, and yeast vaginitis, estimated to affect one billion women each year (the rate for urinary tract infection alone is 0.5 cases per person per year), means that the likelihood of infection is high. Indeed, the presence of pathogens dominating the vagina increases severalfold the likelihood that a woman will develop a symptomatic infection. In short, an abnormal microbiota may indeed lead to a symptomatic vaginal or bladder infection.

The concept of restoring the Lactobacillus content of the vaginal microbiota as a barrier to prevent infection was first conceived by Canadian urologist Andrew Bruce in the early 1970s. Extensive research since then has shown that certain Lactobacillus strains are able to colonize the vagina following vaginal suppository use and reduce the risk of urinary tract infection, yeast vaginitis , and bacterial vaginosis . Strain selection at that time, and even recently, has been based upon in vitro tests and source of the strains,but human studies provide the definitive answer to whether or not strains can function as probiotics.5,13

A study on the prevention of urinary tract infection entailed once-weekly vaginal administration of a suppository containing 109 L. rhamnosus GR-1 and L. fermentum B-54 for 1 year and comparing the rate of urinary tract infection occurrence with that in the previous year in 25 women. There was a significant reduction in urinary tract infection during lactobacillus use (from an average of six episodes per year to 1.6 episodes per year [30%]). No side effects were reported. This compares favorably with two studies that used daily antibiotic therapy to prevent urinary tract infection. The first was a randomized study of 64 patients with a history of recurrent urinary tract infections given trimethoprim (100 mg) at night for 1 year or methenamine hippurate (1,000 mg) every 12 hr or asked to cleanse the perineum (especially the periurethral area) twice daily with povidone-iodine solution .In this study, the urinary tract infection recurrence rates fell from 6 in the previous year to 2.1, 2.0, and 2.2, respectively, for the three groups.5,13

The second study was an 18-year assessment of 219 women given one of three nitrofurantoin regimens daily for 1 year. The mean incidence of urinary tract infection fell from 6.9 per year to 1.3 per year. Notably, 14% of patients were allergic to the antibiotic, and 40% reported at least one adverse side effect, with nausea, gastrointestinal, genitourinary, and skin effects being the most common. In addition, 25.6% of 43 patients taking 50 mg of microcrystalline nitrofurantoin stopped prematurely as a result of an adverse event. Even the use of another antibiotic, cefaclor, 250 mg daily, in 37 patients resulted in an average of 2.4 breakthrough infections per year; 12.8% reported a side effect, and 7.7% stopped taking the drug. In short, Lactobacillus therapy taken once per week with no side effects resulted in as low a rate of urinary tract infection as several daily antibiotic regimens with numerous side effects. While a larger phase three trial has not been performed with Lactobacillus strains GR-1 and B-54, the phase two findings are worthy of note.

In terms of preventing or treating bacterial vaginosis, recent studies have shown that daily ingestion of capsules containing L. rhamnosus GR-1 and L. fermentum RC-14 by 19 women with a bacterial vaginosis microbiota resulted in a normal microbiota (by Nugent scoring) in 81% of cases, compared to 50% in women given placebo.This is not yet sufficient evidence to use oral probiotics for symptomatic bacterial vaginosis treatment, but it does illustrate the potential to reduce the incidence of recurrent bacterial vaginosis that is common after antibiotic treatment .Another study, the results of which are only available on a web site, show that L. crispatus CTV05 given vaginally after metronidazole treatment for bacterial vaginosis resulted in a clinical cure at 30 days in subjects colonized by lactobacilli (70%) compared to noncolonized (47%) patients receiving placebo. Further studies with vaginal Lactobacillus treatment of bacterial vaginosis that are more likely to deliver lactobacilli in higher numbers and more quickly than oral ingestion are warranted. Indeed, certain Lactobacillus strains, including L. crispatus CTV05, L. rhamnosus GR-1, and L. fermentum RC-14, are able to remain in the vagina for several months after insertion.5,13

The prevention or resolution of bacterial vaginosis is particularly important in women at risk of human immunodeficiency virus (HIV) infection. Studies have shown that women with bacterial vaginosis (no lactobacilli) are at significantly increased risk of HIV .Studies of 94 prostitutes in Madagascar showed bacterial vaginosis prevalence of 85% ;a study in Malawi showed an odds ratio of 3.0 (95% confidence interval, 2.4 to 3.8) for an association between bacterial vaginosis and HIV;another Malawi study of 1,196 HIV-seronegative women showed that bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio 3.7) and postnatal HIV seroconversion (adjusted rate ratio 2.3) ;a cross-sectional study of 144 female commercial sex workers in Chiang Mai, Thailand, found a significant association between bacterial vaginosis and seropositivity for HIV (odds ratio, 2.7; 95% confidence interval, 10.3 to 5.0) ;and a study of 4,718 women in Uganda showed an adjusted odds ratio of HIV-1 infection and bacterial vaginosis of 2.08 (95% confidence interval, 1.48 to 2.94)

The depletion of lactobacilli and the risk of HIV was further illustrated in a study of 657 HIV-1-seronegative women in Kenya, where only 26% were colonized with Lactobacillus species, and the absence of these organisms was associated with an increased risk of acquiring HIV-1 infection (hazard ratio, 2.0; 95% confidence interval, 1.2 to 3.5) .The authors concluded that treatment of bacterial vaginosis and promotion of vaginal lactobacilli may reduce a woman's risk of acquiring HIV-1, gonorrhea, and trichomoniasis.5,13

Having shown that certain Lactobacillus strains can colonize the vagina, this raises the questions of whether and how probiotics can reduce the risk of HIV infection .As stated earlier, supernatants from the strains L. rhamnosus GR-1 and L. fermentum RC-14 can inactivate viruses within minutes. It is presumed that a simple acidification of the vagina could affect HIV, but whether other mechanisms such as blocking receptor binding of the virus to CD4 Cells are at work remains to be investigated. Given the failure of current management and interventional steps to halt the AIDS epidemic, use of oral or vaginal lactobacilli appears worthy of consideration, especially given that they can be delivered relatively inexpensively to large numbers of people on the African continent, where drug supplies are often inaccessible or financially prohibitive.5,13

Another potential application is for pregnant women to reduce the risk of bacterial vaginosis infection associated with infant mortality and preterm labor. Oral probiotics would be particularly useful in this case, as they can be administered safely during pregnancy. For reasons not yet known, some lactobacilli, such as L. rhamnosus GG and L. acidophilus NCFM, appear to be not well suited for the urogenital tract, while products on the market such as the vaginal suppository Fermalac, comprising L. rhamnosus and other strains (Rosell, Montreal, Canada), and have no peer-reviewed studies proving eradication of bacterial vaginosis. Thus, for clinical practice at present, there are few clinically proven, commercially available options to antibiotic and antifungal therapy for urogenital infections and antiviral drugs for HIV spread.5,13

c) Cancer:-
The ability of lactobacilli and bifidobacteria to modify the gut microbiota and reduce the risk of cancer is in part due to their ability to decrease ?-glucuronidase and carcinogen levels . Cancer recurrences at other sites, such as the urinary bladder, also appear to be reduced by intestinal instillation of probiotics, including L. casei Shirota (the strain present in Yakult, a Japanese milk-based drink taken by an estimated 26 million people every day). In vitro studies with L. rhamnosus GG and bifidobacteria and an in vivo study with L. rhamnosus GG and LC-705 and a Propionibacterium sp. showed a decrease in availability of carcinogenic aflatoxin in the lumen . Increased activity of glutathione transferase (induced by Bifidobacterium longum and lactulose and resistant starch), colonic NADPH-cytochrome P450 reductase, and enhanced removal of O6-methylguanine from colonic mucosa may also play a role in disease prevention. Fermentation products such as butyrate and lactate or a simple decrease in gut transit time could also be important. However, definitive clinical conclusions require efficacy studies in humans.5,13

d) Mucosal Immunity:-
Studies with L. casei Shirota injected into mice showed a significant increase in natural killer cell activity from mesenteric node cells but not of Peyer's patch cells or spleen cells, supporting the concept that some probiotic strains can enhance the innate immune response. Other animal studies clearly indicate that probiotic strains can modify immune parameters. Mice were fed daily with 109 L. rhamnosus (HN001, DR20), L. acidophilus (HN017), or B. lactis (HN019, DR10), and their immune function was assessed on days 10 and 28. The phagocytic activity of peripheral blood leukocytes and peritoneal macrophages increased significantly compared with the control mice. The proliferative responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen) were also significantly enhanced in mice given different probiotic strains, and spleen cells produced significantly higher amounts of gamma interferon in response to stimulation with concanavalin A.

Dietary consumption of B. lactis HN019 and L. rhamnosus HN001 in randomized, placebo-controlled human studies showed measurable enhancement of immune parameters in the elderly. The precise mechanisms of action remain to be established in patients, but the ability of Lactobacillus strains to activate macrophages and stimulate secretory IgA and neutrophils without release of inflammatory cytokines could be important. It should also be recognized that not all immune effects are necessarily beneficial to the host. As Perdigon and Holgado rightly point out, the major cell wall component of lactobacilli, muramyldipeptide, can be pyrogenic, and some Lactobacillus strains can enhance the Th1 proinflammatory pathway and would not be appropriate for mucosal immunity. The dosage and duration of therapy must also be considered so as to optimally enhance and not suppress immunity.5,13

The use of lactic acid bacteria, such as L. plantarum NCIMB 8826, to deliver vaccines is being tested. This strain is being tested to deliver nontoxic tetanus toxin fragment C, and three types of constructs induced strong specific immune responses in mice. Future studies of this nature will explore the extent to which lactobacilli can immunize against various pathogens that attack the mucosal surfaces of the mouth, intestine, vagina, and respiratory tract.5,13

e) Allergy:-
The composition of the vaginal microbiota has been shown to influence the ultimate asthmatic condition of children. In one Danish study of 2,927 women and their 3,003 infants, maternal vaginal colonization with Ureaplasma urealyticum during pregnancy was associated with infant wheezing (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.6), but not with asthma during the fifth year of life, while maternal colonization with staphylococci (odds ratio, 2.2; 95% confidence interval, 1.4 to 3.4) and use of antibiotics in pregnancy (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.6) were associated with asthma.5,13
As stated earlier, the application of probiotics to prevent allergic reactions became more prominent with the double-blind, randomized, placebo-controlled trial showing that L. rhamnosus GG given to pregnant women for 4 weeks prior to delivery and then to newborn children at high risk of allergy for 6 months caused a significant reduction in early atopic disease. Further clinical studies with L. rhamnosus GG and B. lactis BB-12 appear to have been useful in infants allergic to cow's milk . The current understanding suggests that the probiotic organisms reverse increased intestinal permeability, enhance gut-specific IgA responses, promote gut barrier function through restoration of normal microbes, and enhance transforming growth factor beta and interleukin-10 production as well as cytokines that promote production of IgE antibodies. The role of T-helper 1 (Th1) enhancement and T-helper 2 (Th2) reduction remains to be proven.5,13

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