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Probiotics, prebiotics and child health: where are we going?

Changes in gastrointestinal (GI) bacteria caused by diet, antibiotics or other factors could alter enteric and systemic immune functions; changing the gut microflora composition by diet supplementation with specific live microbiota (probiotics) may be beneficial. The 'natural' target of ingested probiotics is the intestine, its microflora and associated immune system. Most published data concern use of probiotics to prevent and treat GI infections. Evidence for possible beneficial effects on mucosal barrier dysfunctions, including food allergy, inflammatory bowel disease, and respiratory and urinary tract infections, is emerging. The role of prebiotics (non-digestible oligosaccharides that reduce the growth or virulence of pathogens and induce systemic effects) is being investigated. Preliminary studies indicate that prebiotics may be useful dietary adjuncts for managing GI infections. Prebiotic and probiotic use in infants is attempting to modify a complex microbial ecosystem. Better understanding of the long-term effects of these interventions on infant gut microflora is an important goal.

Child↗

Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies?

Studies in gnotobiotic animals have suggested that the intestinal bacterial flora may play an important role in priming the immune system during ontogeny to limit dysfunctional responses, including allergy. Prospective clinical studies have identified a higher incidence of allergy expression in early childhood among children who have low enteric populations of lactic acid bacteria (LAB), such as lactobacilli and bifidobacteria, further supporting a role for gut-colonizing bacteria in regulating immunological atopy. There is some evidence to suggest that supplementing the human diet with probiotic LAB might combat both allergy development and expression of atopy in allergy sufferers; however, definitive information, in the form of controlled intervention trials, remains scant. Recent immunological evidence has indicated that certain strains of LAB can stimulate the production of type I and II interferons and pro-interferon monokines (IL-12 and IL-18), following contact with the immune system; therefore, probiotic forms of immunoregulatory LAB could be used as dietary supplements to modify the gut microflora and provide pro-T helper cell 1 (Th1) STAT-activating signals sufficient to deviate the immune phenotype and correct the Th2-type bias which promotes allergy. This review outlines the clinical and laboratory evidence of a role for LAB in combating allergies, and attempts to explain this phenomenon in terms of our current understanding of immunoregulatory signals produced by gut-colonizing microbes.

Adjuvants, Immunologic↗

Safety and tolerance of a probiotic formula in early infancy comparing two probiotic agents: a pilot study.

OBJECTIVE: To compare the safety and tolerance of two formulas, supplemented with different probiotic agents, in early infancy. DESIGN: Prospective randomized placebo-controlled trial. SETTING: Clinics of a University Medical Center. SUBJECTS: Full-term healthy infants aged less than 4 months. INTERVENTION: Infants were randomly assigned for 4 weeks to a standard milk-based formula supplemented with either Bifidobacterium lactis (BB-12), Lactobacillus reuteri (ATCC 55730) or a probiotics-free formula. MEASURES OF OUTCOME: Growth parameters, daily characteristics of feeding, stooling and behavior, and side effects. RESULTS: Fifty-nine infants, aged 3-65 days, were included. Subjects in all three groups were similar at entry in terms of gestational age, birth weight, sex, growth parameters and breast feeding rate prior to the study. The supplemented formulas were well accepted and did not reveal any adverse effects. A comparison of growth parameters, and variables of feeding, stooling and crying and irritability did not reveal any significant differences between groups. CONCLUSIONS: The use of formula supplemented with either Lactobacillus reuteri or Bifidobacterium lactis in early infancy, was safe, well tolerated and did not adversely affect growth, stooling habits or infant behavior.

Analysis of Variance↗

Atopic dermatitis and the 'hygiene hypothesis': too clean to be true?

BACKGROUND: The so-called 'hygiene hypothesis' postulates an inverse relationship between atopic dermatitis (AD) and an environment that leads to increased pathogen exposure. OBJECTIVES: We sought to systematically identify, summarize and critically appraise: (i) the epidemiological evidence to suggest that environmental exposures that lead to an increase in microbial burden reduce the risk of AD; (ii) whether any specific infections have been shown to reduce AD risk; (iii) whether there is a link between immunizations, use of antibiotics and AD risk; and (iv) to comment on the new therapeutic approaches in AD that have evolved out of the 'hygiene hypothesis'. METHODS: We searched Medline from 1966 until August 2004 to identify relevant studies for inclusion. Differences in study design and populations did not allow formal meta-analysis. Studies were therefore described qualitatively. RESULTS: We identified 64 studies that were relevant to our review, 27 (42%) of which were of prospective design. There was prospective evidence to support an inverse relationship between AD and endotoxins, early day care and animal exposure. Two well-designed cohort studies have found a positive association between infections in early life and AD, and measles vaccination and AD. Antibiotic use was consistently associated with an increase in AD risk even into the antenatal period, although a few studies did not reach conventional statistical significance. A few small randomized controlled trials have suggested that probiotics can reduce AD severity and that probiotics may also be able to prevent AD to some degree. CONCLUSIONS: Although population-based studies have suggested a consistent inverse relationship between AD and increasing family size, this does not seem to be explained by a straightforward increased exposure to a single environmental pathogen. The effect seen with early day care, endotoxin and animal exposure may be due to a nonpathogenic microbial stimulus of a chronic or recurrent nature. This would also explain the risk increase associated with antibiotic use. Caution should prevail in the prescribing of antibiotics early in life, especially in children with a family history of AD. Larger well-designed pragmatic trials on probiotics and the prevention and treatment of AD are now needed to inform whether such interventions should be used in routine clinical practice.

Adolescent↗

Use of fermented foods to combat stunting and failure to thrive.

OBJECTIVES: With the adoption of vigorous child survival strategies, infant and child mortalities in India have declined significantly, even among the poorest, most undernourished segments of the population. Of the surviving infants and children, however, many remain stunted and undernourished. The present study was based on the hypothesis that failure to thrive is the result of damage to the gut epithelium incurred during repeated bouts of gastrointestinal infections. Promoting the regeneration of the damaged gut epithelium through the use of lactobacillus-rich fermented foods may yield beneficial results. This low-cost procedure can be widely used, even in poor communities. The objectives of this study were to investigate the effect in poor Indian communities of supplementation with a probiotic on the growth of children (aged 2 to 5 years) with growth retardation and assess the difference in morbidity between those receiving the supplement (n = 50) and the control group (n = 50), mainly with respect to the frequency, severity, and duration of diarrheal episodes. METHODS: One hundred children aged 2 to 5 y from an urban slum of New Delhi were matched for their age (+/-36 d), sex and weight (+/-1 kg) and assigned to one of two groups (experimental n= 50 and control n= 50). The experimental group received a probiotic supplement (50 ml curd containing Lactobacillus acidophilus) and the control group received an isocaloric supplement daily for 6 mo. Weight, height, and morbidity profile with respect to diarrhea, fever, cough, and cold was recorded. RESULTS: Increases in weight (P < 0.002) and height (P < 0.001) were significantly greater in the experimental group than in the control group. In addition, after 6 mo, of supplementation, there were fewer cases of diarrhea (P < 0.005) and fever (P < 0.001) in the intervention group then in the control group. CONCLUSIONS: From this study, it can be concluded that 6 mo of probiotic supplementation may be beneficial with respect to decrease in diarrheal morbidity and accelerated growth in the experimental group.

Body Height↗

Evaluation of Lactobacillus pentosus WE7 for prevention of diarrhea in neonatal foals.

OBJECTIVE: To evaluate the efficacy of Lactobacillus pentosus WE7, an equine-origin organism with potentially beneficial in vitro properties, as a probiotic for prevention of neonatal diarrhea in foals. DESIGN: Randomized controlled clinical trial. ANIMALS: 153 foals. PROCEDURE: Foals were enrolled at 24 to 48 hours of age and randomly assigned to treatment or control groups. The treatment group received approximately 2 x 10(11) CFU of freeze-dried L. pentosus WE7 orally once daily for 7 days, whereas the control group received a placebo. Clinical monitoring was performed for 14 days. RESULTS: Probiotic administration was significantly associated with development of signs of depression, anorexia, and colic and the need for veterinary examination and treatment. Probiotic-treated foals also had more days of diarrhea, compared with the control group, although not significantly. In a multivariate model, probiotic administration was significantly associated with development of diarrhea and diarrhea plus additional clinical abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L. pentosus WE7 did not prevent diarrhea; rather, it was associated with development of diarrhea and, most importantly, development of diarrhea plus additional clinical abnormalities and the need for veterinary intervention. The promising in vitro properties of L. pentosus WE7 were not evident in vivo. Results raise concern about the variety of untested probiotic products that are commercially available. Safety and efficacy testing needs to be performed for all potential equine probiotics.

Administration, Oral↗

Fermented milks, probiotic cultures, and colon cancer.

Colorectal cancer (CRC) is a major cause of death from cancer in the Western world. Approximately 70% of CRC is associated with environmental factors, probably mainly the diet. There is interest in the potential protective role of fermented milks containing probiotic cultures against CRC. This article analyzes the existing data from human, animal, and in vitro studies that explore whether consumption of milks fermented with probiotic cultures could play a role in colon cancer risk reduction. Cohort studies have failed to detect significant effects, but most case-control studies favor a protective role of fermented milks against colon cancer. Interventional studies have shown a shift of intermediate markers of CRC risk in human subjects from a high- to low-risk pattern after ingestion of fermented milks or probiotics. Animal studies consistently show a reduction in chemically induced colorectal tumor incidence and aberrant crypt formation accompanying probiotic administration. In vitro studies also provide evidence of protection, and permit a better understanding of active compounds involved, and of the mechanisms underlying their anticarcinogenic effects. Probiotics may beneficially modulate several major intestinal functions: detoxification, colonic fermentation, transit, and immune status, which may accompany the development of colon cancer. Although the evidence is not conclusive and much further research is required, the data reviewed constitute a promising body of evidence supporting the protective role of milks fermented with probiotic cultures in colon cancer risk reduction.

Animals↗

Tetracycline susceptibility of the ingested Lactobacillus acidophilus LaCH-5 and Bifidobacterium animalis subsp. lactis Bb-12 strains during antibiotic/probiotic intervention.

We investigated the effects of oral therapy with doxycycline, a tetracycline group antibiotic, on the gastrointestinal (GI) survival and tetracycline susceptibility of probiotic strains Lactobacillus acidophilus LaCH-5 and Bifidobacterium animalis subsp. lactis Bb-12. In addition, the influence of doxycycline therapy on the diversity of the predominant faecal microbiota was evaluated by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Faecal samples from the antibiotic group (receiving antibiotics and probiotics) and the control group (receiving probiotics only) were analysed for anaerobically and aerobically growing bacteria, bifidobacteria and lactic acid bacteria as well as for the dominant microbiota. Although doxycycline consumption did not have a large impact on GI survival of the probiotics, it had a detrimental effect on the bifidobacteria and on the diversity of the dominant faecal microbiota. A higher proportion of tetracycline-resistant anaerobically growing bacteria and bifidobacteria was detected in the antibiotic group than in the control group. Several antibiotic group subjects had faecal B. animalis subsp. lactis Bb-12-like isolates with reduced tetracycline susceptibility. This was unlikely to be due to the acquisition of novel tetracycline resistance determinants, since only tet(W), which is also present in the ingested B. animalis subsp. lactis Bb-12, was found in the resistant isolates. Thus, concomitant ingestion of probiotic L. acidophilus LaCH-5 and B. animalis subsp. lactis Bb-12 with the antibiotic did not generate a safety risk regarding the possible GI transfer of tetracycline resistance genes to the ingested strains.

Adult↗

Effects of probiotics on the severity of experimental acute pancreatitis.

OBJECTIVE: This study was designed to evaluate the effects of probiotics on the severity of experimental acute pancreatitis. DESIGN: Experimental study. SETTING: Experiments were done in a laboratory at Haydarpasa Numune Teaching and Research Hospital. SUBJECTS: A total of 50 Wistar rats were randomly divided into five groups. INTERVENTIONS: Group 1 was control group. Group 2 received an intraperitoneal injection of a 20% solution in 0.15 mol/l NaCL. Group 3 was injected NaCL and fed with probiotics. Acute pancreatitis was induced in rats by intrperitoneal injection of L-Arginine in groups 4 and 5. The rats in group 5 were treated with probiotics. The pancreas was removed for histologic examination. Evaluation of the pathologic changes was done by a new combined histopathologic grading scale. RESULTS: The mean scores of fibrosis, acinar cell loss, oedema, parenchymal necrosis, mononuclear cells infiltration, polymorphonuclear leucocytes infiltration, ductal damage and atypical reactive regeneration in group 5 were significantly lower than group 4. CONCLUSIONS: We demonstrated that enteral feedings with added probiotics can reduce the severity of acute pancreatitis. SPONSORSHIP: None.

Animals↗

Daily ingestion of fermented milk containing Lactobacillus casei DN114001 improves innate-defense capacity in healthy middle-aged people.

Different lactic acid bacteria have often been administered as a dietary means to enhance immune system activity. Based on this statement, the aim of the current work was to test the effects of a Lactobacillus casei DN114001 fermented milk consumption on the immune response capacity in middle-age volunteers. Forty-five healthy volunteers, 24 women and 21 men (aged: 51-58 years), were randomized into two groups to receive three cups per day of a L. casei DN114001 (10(8)-10(10) ufc/g) fermented milk (n = 23), or placebo (n = 22), during an 8-week period. Measurements were performed before (day 0), and after the nutritional intervention (day 56). After the trial, no changes in immune cell proportions were detected, but the probiotic-treated group increased oxidative burst capacity of monocytes (probiotic group: p = 0.029; placebo group: p = 0.625), as well as NK cells tumoricidal activity (probiotic group: p = 0.023; placebo group: p = 0.125). Results showed that daily intake of fermented milk containing Lactobacillus casei DN114001 could have a positive effect in modulating the innate immune defense in healthy-middle-age people.

Animals↗

Atopic eczema. What has caused the epidemic in industrialised countries and can early intervention modify the natural history of atopic eczema?

Atopic eczema (AE) has a lifetime prevalence of between 15 and 20% in industrialized countries, but a very low prevalence in rural Africa. The 'atopic eczema epidemic' has developed in industrialized countries within the last four decades. The disease has a strong genetic influence, so environmental factors must be responsible for the dramatic increase in disease prevalence. It is therefore fair to consider what interventions may change its prevalence. In this article, several factors are considered: the increased number of doctors in industrialized countries, the development of drugs like topical steroids and emollients, the 'demanding parents' and 'old mother' syndromes, introduction of vaccination programmes, allergen exposure, breastfeeding and the possible beneficial effects of probiotics. In 90% of children with AE, onset is before the age of 5. Its course runs over years. Approximately two out of three outgrow the disease between 7 and 12 years of age. Although its cause is unknown, type I allergic reactions are common and allergen avoidance has been attempted in many studies as a preventive measure in atopic dermatitis. However, results are rather disappointing. The use of probiotics, i.e. daily intake of Lactobacillus, has proven effective in preventing, or at least delaying, the development of atopic eczema. So has breastfeeding, although some studies cannot confirm its beneficial effect. Therapeutic interventions using antihistamines, desensitisation and control of skin inflammation using topical steroids have not proven successful in shortening the course of atopic eczema, although controlled studies are lacking. The use of emollients has, however, a documented effect in up to one of three children with mild atopic eczema. It will be interesting to observe if the new topical immuno-modulators, tacrolimus and pimecrolimus, may be able to shorten the natural course of the disease.

Journal Article↗

Giardiasis: pathophysiology and management.

Giardia, a common human parasite, can cause significant morbidity; however, natural medicine has great potential to influence the course of Giardia infection. The most beneficial way to treat giardiasis naturally may be through a combination approach, utilizing both nutritional interventions and phytotherapeutic agents. Nutritional intervention aims to reduce the acute symptoms of Giardia and help clear the infection. This can best be achieved by consuming a whole-food based, high-fiber, diet that is low in fat, lactose, and refined sugars. Additionally, ingestion of probiotics and wheat germ assists in parasite clearance. Numerous medicinal herbs show promise in the treatment of giardiasis. Berberine-containing herbs, garlic, and the Ayurvedic formulation Pippali rasayana currently have the most clinical evidence supporting their use. Blending the nutritional interventions and phytotherapeutic agents outlined in this article can minimize Giardia symptomatology and aid clearance of the parasite, without significant ill effects. As such, this therapeutic strategy should be considered the first-line approach. Antibiotic use may best be reserved for cases that fail to respond to initial treatment with natural measures.

Animals↗

Moving from recommendation to implementation and audit: part 2. Review of interventions and audit.

There are multiple interventions available that may help to control the development and spread of resistance to antimicrobial agents in bacteria implicated in community-acquired respiratory tract infections. Unfortunately, very few studies have assessed the effectiveness of these interventions using objective end-points, such as reduction in resistance rates and improvement in clinical outcomes. Most interventions are centered on reducing inappropriate or unnecessary use of antibiotics; others focus on reducing disease burden and bacterial colonization. With regard to antibiotic use, efforts should be concentrated at both the prescriber and consumer levels. Interventions that target prescribers include: provision of educational materials; strategies and tools to improve diagnosis; implementation of practice guidelines; personalized interactive sessions with feedback on the practice profile; and use of delayed prescription and alternative prescribing strategies. Optimal results are usually obtained when these interventions are combined with consumer education. Regulatory interventions (e.g. licensing regulations and controlled access to drugs), restrictions in the use of agents for growth promotion in animals, and use of nonantimicrobial therapies (e.g. probiotics) may help further to reduce inappropriate antibiotic use and thereby decrease the selective pressure for development of resistance. Infection-control strategies, public health measures, vaccination programs, and new antibiotics all have a role in minimizing the spread of resistant organisms. Ideally, resistance-control programs should include predefined criteria for success and integral audit processes based on objective end-points (antibiotic use, resistance trends, and health outcomes). Standardization of data collection is imperative so that the relative merits of various interventions can be compared. Effective implementation and audit of interventions is often difficult in developing countries owing to poor health-care infrastructures, lack of resources, poor education/training, and minimal regulatory controls on the supply and quality of antimicrobials. Substantial support from governments and health-care organizations across the globe is required to initiate and sustain effective intervention programs to control antimicrobial resistance.

Anti-Bacterial Agents↗

Inflammatory bowel disease pathogenesis: therapeutic implications.

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving environmental, genetic, microbial, and immune factors. Therefore, treatment should target components that either predispose to or mediate the chronic inflammatory response of IBD. At the moment it is assumed that all components are necessary to have the typical manifestations of IBD but, in reality, it is unclear to what extent each factor contributes to the disease process, and whether some are more important than others. In addition, some factors are not practical targets; for example, environmental factors are poorly defined, too numerous, and require changes that cannot be implemented by the physician or the patient alone. The same is true for genetic factors that are still not amenable to therapeutic manipulations for technical and ethical reasons. This leaves microbial and immune factors as the two categories that can be selected for therapeutic intervention and where all current treatments are focused. The commensal gut flora can be qualitatively or quantitatively modified with antibiotics, probiotics, or diet, and a better characterization of enteric bacteria strains should help greatly in developing more effective therapies. Most current drugs are focused on inhibiting pro-inflammatory molecules produced by immune cells, including biological agents that block specific cytokines such as tumor necrosis factor-alpha. It is anticipated that combination therapies targeting multiple pathogenic components will prove more effective than those blocking single components of IBD pathogenesis.

Colitis, Ulcerative↗

Daily intake of probiotic as well as conventional yogurt has a stimulating effect on cellular immunity in young healthy women.

BACKGROUND/AIMS: The aim of this work was to study the effects of daily yogurt consumption on the cellular immunity of young healthy women and to compare a conventional with a probiotic product. METHODS: 33 young healthy women (22-29 years) consumed 100 g/day of either probiotic or conventional commercially available yogurt for 2 weeks and 200 g/day for another 2 weeks followed by a 2-week washout period with no fermented food at all. Before the intervention and after each phase, a complete white blood count was done, the percentage of activated CD69+ T lymphocytes after stimulation of whole blood with pokeweed mitogen was determined as well as the natural cytotoxicity of peripheral blood mononuclear cells against a human erythroleukemic target cell line (K562). All analyses were done by flow cytometry. RESULTS: In the probiotic group only, the numbers of cytotoxic T lymphocytes (CD3+CD16+CD56+) increased significantly (+30.8% with p = 0.001, +22.1 and +32.7% with p = 0.002, for T2, T3 and T4 compared to T1). There were no major changes for other cell populations, and all remained within the physiological range. In both groups, the expression of CD69 on T lymphocytes increased after yogurt consumption, especially on CD8+ (conventional: T2 +23%, T3 +27.2%, probiotic: T2 +15.7%; T3 +10.8% compared to T1) and to a lesser extent on CD4+ (conventional: T2 +7.7%, T3 +14.9%, probiotic: T2 +4% compared to T1. The cytotoxic activity also augmented following the intake, this effect persisting after cessation of consumption. However, there were no significant differences between the probiotic and the conventional yogurt group. CONCLUSION: Daily yogurt intake has a stimulating effect on cellular immune functions, but in this study the probiotic product did not perform better than the traditional one.

Adult↗

[Nutrition, probiotics, antibiotics, antioxidative therapy, endoscopy in chronic pancreatitis].

Treatment of chronic pancreatitis is dependent on the stage of the disease and consists of several arms: treatment of pain when ever possible according to its pathogenesis; treatment of complications primarily by interventional endoscopy, in cases of failure by surgery; therapy of exocrine insufficiency with porcine pancreatic extracts; treatment of endocrine insufficiency with insulin. Pseudocysts can be drained according to their location by either the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenoses of the main pancreatic duct can be handled by placement of a plastic stent; similarily to treatment of biliary strictures. Stones leading to obstruction of the main pancreatic duct can be disintegrated by extracorporeal shock wave lithotripsy (ESWL) and the fragments removed by endoscopy after papillotomy. Transgastral endoscopic drainage of retroperitoneal necroses is still experimental. Prospective randomized multicenter trials comparing surgery with interventional endoscopy are still lacking. Failure of endoscopic therapy or suspicion of tumor is clearly an indication for surgery. There is no need for a specific diet in patients with chronic pancreatitis without having diabetes. In severe attacks, clinically similar to acute pancreatitis, enteral nutrition via a jejunal tube is replacing parenteral nutrition. However, prospective comparative trials are still mandatory. Prophylactic application of antibiotics in patients with pancreatic necrosis is again under debate. Whether probiotics are capable to decrease the risk of secondary pancreatic infection of necrosis has not been thoroughly studied. The hypothesis that capture of oxygen free radicals by drugs such as selenium may prevent frequency and severity of acute relapses has also not been proven.

Anti-Bacterial Agents↗

Faecal SIgA secretion in infants fed on pre- or probiotic infant formula.

Secretory immunoglobulin A (SIgA) plays an important role in the defence of the gastrointestinal tract. The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses. Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aimed at studying the effects of standard, prebiotic and probiotic infant formulas on the faecal SIgA levels. At birth, infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a randomized, double-blind fashion. Nineteen infants received standard infant formula; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 x 10(9) cfu Bifidobacterium animalis/100 ml formula. Faecal samples were taken on postnatal day 5, day 10, wk 4 and every 4 wk thereafter until wk 32. SIgA in faeces was determined by an enzyme-linked immunosorbent assay. During the intervention, infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the standard formula-fed infants reaching statistical significance at the age of 16 wk. In contrast, infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the standard formula group. Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion. Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend.

Breast Feeding↗

The potential for probiotics to prevent bacterial vaginosis and preterm labor.

Infections of the urogenital tract in women represent a major burden on the quality of life of women and on the health care system of Canada and other countries. Complications arising from bacterial vaginosis (BV) include increased risk of sexually transmitted diseases including human immunodeficiency virus and elevated risk of preterm birth (PTB). Pharmaceutical interventions, such as antibiotics, have been suboptimally effective and have failed to reduce the incidence of PTB. The absence of lactobacilli in the vagina, a specific feature of BV, raises the question as to whether restoration of lactobacilli, by probiotic therapy, can restore the normal flora and improve the chances of having a healthy term pregnancy. The rationale for probiotic use in pregnant women is quite strong. Certain lactobacilli strains can safely colonize the vagina after oral and vaginal administration, displace and kill pathogens including Gardnerella vaginalis and Escherichia coli, and modulate the immune response to interfere with the inflammatory cascade that leads to PTB. Additional attributes of probiotics include their potential to degrade lipids and enhance cytokine levels, which promote embryo development. In a society that focuses on disease rather than health and drug therapy rather than natural preventive measures, it will take some effort to get remedies such as probiotics into mainstream care. Perhaps the escalating health care budgets and emergence of "superbugs" will provide the incentives to put in place clinical trials designed to evaluate how best to use the commensal organisms that, after all, make up more of our body than human cells, and without which none of us would survive.

Female↗