IMPORTANCE OF PROBIOTICS AND PREBIOTICS IN PEDIATRIC DISORDERS

THE IMPORTANCE OF PROBIOTICS AND PREBIOTICS IN PEDIATRIC DISORDERS

Kholdarova Gulsanam Akramjon qizi

Student, Namangan institute of engineering and technology,

Uzbekistan, Namangan

ABSTRACT

Probiotics and prebiotics have a major influence on gastro-intestinal composition. This review analysis if this change in flora composition healthcare benefits in children. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics. The administration of two prebiotics (inulin and fructo-oligosaccharide) was not effective for preventing diarrhea and antibiotic associated diarrhea.

Keywords: probiotics, prebiotics, diarrhea, pediatric disorders, healthcare benefits, lactobacillus, bifidobacteria, colic and extraintestinal infections.

The gastrointestinal (GI) tract is harboring a diverse array of commensal microbes that act like a separate eco-system. The GI flora can be considered as an organ within an organ contributing to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens and development of the immune response. Probiotics are non-pathogenic live micro-organisms that, when consumed in adequate amounts, have a positive effect on the health of the host. Although probiotics are today a “hot topic”, they are not new. Most probiotics are registered as food supplement, and thus do not have to fulfill the quality requirements for medication. Research on the mechanisms of action of specific strains and clinical trials with commercialized products are mandatory. In vitro effects of a strain may display opposite behavior in vivo. Effects demonstrated for one strain cannot be extrapolated to other strains, even if they be long to the same species. Only these commercialized products for which convincing data are  available can be recommended for medical use. Since some commercialized products are combinations of different strains, clinical testing of each combination of each product is mandatory as they may have synergetic or contradictory effects. Moreover, dosage and duration of administration should be taken into account as different doses and different duration may have opposite effects. Prebiotics are non-digestible food ingredients that stimulate the growth and/or activity of bacteria in the digestive system in ways claimed to be beneficial to health. Full-spectrum prebiotics provide molecular link-lengths from 2-64 links per molecule, and nourish bacteria throughout the colon, e.g. oligofructose-enriched inulin. In infant formula, most of the time galacto-oligosaccharides (GOS) and/or fructo-oligosaccharides (FOS) are used. The majority of research done on prebiotics is based on full-spectrum prebiotics. More and more “synbiotics” come on the market. These are combinations of a prebiotic and most of the time several strains of probiotics. Manufacturers market these products by listing all the benefits of each ingredient separately. Whether this marketing strategy is scientifically valid is uncertain. It becomes also more and more difficult to obtain information about the exact strains in different products. The lack of legal protection authorizes competitors to copy successful products without any investments for the company that copies products.

The pooled relative risk in a meta-analysis of 63 RCTs, which included 11,811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P < .001; I(2), 54%; 25 [risk difference, -0.07; 95% CI, -0.10 to -0.05]. Another metaanalysis concluded the number needed to treat was 8. According to a recent meta-analysis, probiotics reduce the risk of AAD in children significantly. Preplanned subgroup analysis showed that reduction of the risk of AAD was associated with the use of L. GG (95% CI 0.15 to 0.6), S. boulardii (95% CI

 0.07-0.6), or B. lactis and Str. thermophilus (95% CI 0.3 to 0.95). For every 7 patients that would develop diarrhea while being treated with antibiotics, one fewer will develop AAD if also receiving probiotics. Only S. boulardii was reported to be effective in Clostridium Difficile (C. Dif.) disease. Recently, a large single-center study showed in elderly that S. boulardii was not effective in preventing the development of AAD or in prevention of C. Dif. infection. In many studies, there is no evidence to support the use of any probiotic to prevent the recurrence of C. Dif. infection or to treat existing C. Dif. diarrhea. In most studies, the probiotic is started together with antibiotic treatment. Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence maintains a protective effect of probiotics in preventing AAD, independent of age. If probiotics are also effective in preventing C. Dif. infection remains debated. None of the trials that reported on adverse events documented any serious side effect. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics. The administration of two prebiotics (inulin and fructo-oligosaccharide) was not effective for preventing diarrhea and AAD.

Almost all studies are focusing on the prevention of AAD; there are no data on efficacy of probiotics or prebiotics in the treatment of AAD, except for very limited data on S boulardii in Clostridium difficile diarrhea. S. boulardii was shown to be effective in secondary prevention; it’s role in primary prevention is poorly defined. There have been no RCTs with probiotics in the treatment of AAD in children.

While some studies with probiotics as a treatment for atopic dermatitis show a benefit, most studies are negative. No benefit was reported from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years. Most reviews conclude that probiotics are not effective in reducing atopic dermatitis. These contradictory results suggest strain specificity or a genetic influence on the efficacy of probiotics in children with atopic dermatitis. A review dealt with dietary exclusions for people with eczema and found little evidence to support any dietary exclusion, apart from avoidance of eggs in infants with suspected egg allergy supported by evidence of sensitization. A review of 13 studies of probiotics for treating established eczema did not show convincing evidence of a clinically worthwhile benefit, an observation that has been substantiated in a subsequent review. No treatment data are available for prebiotics in AD. Probiotics have a long record of safety, which relates primarily to lactobacillus and bifidobacteria. Experience with other forms of probiotic is more limited. There is  no such thing as zero risk, particularly    in the context of certain forms  of host susceptibility. Probiotics are “Generally Regarded As Safe” and side-effects in ambulatory care have almost not been reported. Large scale epidemiological studies in countries where probiotic use is endemic demonstrate (in adults) low rates of systemic infection, between 0.05 and 0.40 %. Administration during pregnancy and early infancy is considered safe. Probiotic compounds may contain hidden allergens of food and may not be safe for subjects with allergy to cow's milk or hen's egg. Documented invasive infections  have been primarily  noted to occur in immuno-compromised adults. Invasive infections in infants and children are exceedingly rare. Two cases of bacteriemia attribuable to Lactobacillus supplementation, with identical molecular clinical and supplement isolates, were recently reported in an infant and a child without underlying gastrointestinal disease or immuno-compromised status. Sepsis with probiotic lactobacilli has been reported in children with short gut. Fungemia with S. boulardii. has been reported in about 50 patients, all with a central venous catheter. Recently, plasmid transfer of antibiotic resistance has been shown to be clinically possible to occur. Long-term use of probiotics under antibiotic selection pressure could cause antibiotic resistance, and the resistance gene could be transferred to other bacteria. Translocation  from the gastro-intestinal tract  in the systemic circulation has not been reported. The case reports on sepsis emphasize that probiotic supplementation should be used with caution in children with indwelling central venous catheters, prolonged hospitalizations, and a recognized or potential compromise of gut mucosal integrity. There is poor public understanding of the concept of risk, in general, and risk/benefit analysis, in particular. Uncertainty persists regarding the potential for transfer of antibiotic resistance with probiotics, but the risk seems to be low with currently available probiotic products. As with other forms of therapeutics, the safety of probiotics should be considered on a strain-by-strain basis. The potential benefits of supplementation should be weighed against the risk of development of an invasive infection resulting from probiotic therapy.

Probiotics and prebiotics have aninfluence on GI flora composition. However, despite large research on the subject, clear indications for their use in treatment and prevention remain scarce even though their administration seems safe and negative effects are scarce. It is difficult to translate heterogeneous-based study results, which are mainly due to varying genera, strains, doses, study settings and measured outcomes, into evidence based recommendations. A recent review analyzed the data from 3 synbiotic studies (N = 475), 10 probiotics studies (N = 933) and 12 prebiotics studies (N = 1563) added to infant formula. Probiotics did not lower the incidence of diarrhea, colic, spitting up regurgitation, crying, restlessness or vomiting.  Prebiotics in formula  did increase weight gain. Prebiotics  increased stool frequency but   had no impact on  stool consistency, the incidence of colic, spitting up / regurgitation, crying, restlessness or vomiting. There was no impact of prebiotics on infections and gastrointestinal microflora. There is not enough evidence to state that supplementation of term infant formula with synbiotics, probiotics or prebiotics does result in improved growth or clinical outcomes in term infants.

Necrotizing enterocolitis (NEC) is a severe condition occurring especially in preterm babies. Abnormal gastrointestinal flora development has been hypothesized as one of the possible etiologic factors. The first publication reporting that L. acidophilus and B. infantis reduced NEC dates back from 1999. Short afterwards, oligofructose was shown to not decrease NEC, which was followed by a negative study showing that seven days of L. GG supplementation starting with the first feed was not effective in reducing the incidence of urinary tract infection, NEC and sepsis in preterm infants. Then, several randomized trials with different lactobacilli and bifidobacteria showed a significant reduction in development of NEC.  Although S. boulardi iwas  shown to ameliorate hypoxia/reoxygenation-induced NECs in young mice, it did not protect for NEC in infants. A Cochrane review concluded in 2008 that enteral probiotic supplementation reduced the incidence of NEC Stage II or more and mortality. No systemic infections or serious adverse events were directly attributed to the administered probiotic microorganism. According to the published trials, the number needed to treat to prevent one case of NECis 21 and 27. However, the centers in which these trails have been performed have a much higher incidence of NEC than most European or North American centers. The recommendation may be different in centers with a high incidence of NEC in which the other measurements to decrease NEC are difficult to apply. The updated Cochrane review  from 2011  comes to different conclusions: enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. The updated review of available evidence supports a change in practice. More studies are needed to assess efficacy in ELBW infants and assess the most effective formulation and dose to be utilized. The debate to give systematically probiotics topreterms or not is still going one. The American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review concluded in 2012 acknowledges that recent Cochrane Reviews support the use of prophylactic probiotics in preterm infants less than 2500 grams to reduce the incidence of NEC, as well as the use of human breast milk rather than formula when possible. There is no clear evidence to support delayed initiation or slow advancement of feeds. However, an expert group of nutritionists and neonatologists  concluded that there is insufficient evidence to recommend routine use of probiotics to decrease NEC. According to this group, there is encouraging data (2b LoE) which justifies the further investigation regarding the efficacy and safety of specific probiotics in circumstances of high local incidence of severe NEC. Other experts suggest that it may become unethical to not give probiotics to preterm babies to decrease NEC.

There are no data available to establish if  synbiotics are superior to probiotics or prebiotics. During the last decade, evidence from multiple good quality clinical research studies resulted in the fact that pre-, pro- and synbiotics can no longer be neglected. However, future research has to focus on specificity, safety, dosage, and combinations.

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