Probiotics in pediatrics

Probiotics are defined to be non-pathogenic strains of organism that are incorporated into the diet to modify gut microbial ecology, leading to beneficial structural and functional changes in the gut. Some probiotics may serve as a barrier for the colonization of pathogens to prevent disease and enhance the immune system. In addition, some may carry out metabolic functions such as helping the fermentation of nondigestible fibres, and storing energy in the form of short-chain fatty acids. Of all the types of gut microbiota, Bifidobacteria and Lactobacilli are considered the two most essential bacteria beneficial to human health while Staphylococci and Clostridia are considered pathogenic to human health.

Formula-fed infants versus breast-fed infants

When comparing formula-fed and breast-fed infants, formula-fed infants' intestinal culture mostly consist of coliforms such as Escherichia coli, Clostridium difficile, bacteroids, and Lactobacilli bacteria. Hence, formula-fed infants have a more complex intestinal microflora than breast-fed infants. In breast-fed infants, Bifidobacteria contribute 80-90% of the microflora, while Lactobacilli and bacteroids constitutes a small amount in the intestine. However, Bacteroides, Veillonella, and Fusobacterium in the intestines start to increase in number after weaning. At this point, the child's intestinal microflora starts to develop in line with that in adults.

Immunity

Complete GI tract

About 80% of all the immunologically active cells are located in the GALT. This implies that microbes in the gut are crucial in contributing to the immunological development of the GALT. It is necessary for the body to establish an efficient microbe-gut immune system interaction because there are about 10¹⁰ to 10¹² prokaryotic organisms that are harbored in an infant's intestine and some are potentially pathogenic.

Studies have been done to examine the gut-tissues of germ-free mice and found that the absence of microbes gave rise to an underdeveloped and sparse mucosal immune system. Characteristics of this underdeveloped mucosal immune system include a lamina propria that does not have IgA plasma cells or CD4 cells, and very small numbers of intraepithelial lymphocytes. This indicates that the mucosal immune system is dependent on gut bateria. Since new born infants do not show an underdeveloped and sparse mucosal immune system, it explains how microbes harbored in an infant's intestine are crucial for the development of a proper mucosal immune system.

Furthermore, intestinal bacteria affect epithelium cell functions through signaling receptors such as Toll-like receptors. The function of the epithelium cell is to regulate immune gut response by controlling T cell differentiation and antibody responses to T cell-dependent antigens. One example is the IgA responses to luminal antigens. When pathogen antigens and gut lumen protein are present, one antibody response to these molecules would be IgA secretion. Hence, microbial colonization has an effect on the IgA responses to antigens in the lumen. Another immune function that microbial colonization gives is the ability to reduce the possibility of immune hyperreactivity such as allergies through inducing modulation of the T-helper type 2 and T-helper type 1 ratio.

Importance of intestinal bacteria on immune function

Lactobacilli and Bifidobacteria are the two of the main types of bacteria that reside in the small intestine. Some commercial strains of these groups of bacteria are used as probiotics. Both bacterial groups may play a role in both local and systemic immunity of the intestine. Aside from providing a gut defense barrier, some strains of these two types of bacteria may secrete antimicrobial substates to inhibit the growth of pathogens.

Intestinal bacteria are also shown to improve the secretory immune function and the intestinal flora such as influencing secretory immunoglobulin A (sIgA) synthesis and sIgA precursors. sIgA is an immunoglobulin that is present in mucosal surfaces. Its function is mainly to protect against the attack of antigens, pathogens, toxins and viruses.

Researches have shown that high bacteroid and Clostridium counts accompanied by low Bifidobacterium counts can lead to an altered immune responses in infants. Premature infants are expected to have intestines that contain non-bifidobacterium species because of their frequent exposure to microbial environments and antibiotic use.

Health effects

Acute diarrhea

As many prevention methods for diarrhea have adverse effects (e.g. intestinal intussusception in the usage of rotavirus vaccine), scientists are now turning to probiotics in hope of using it as a supplement to treat acute diarrhea.^[1] In a review that covered 34 masked, randomized, placebo-controlled trials related to diarrhea and probiotics, it was concluded that there was an overall reduction of 52% in antibiotic associated diarrhea, an 8% reduction in traveller’s diarrhea, and a 34% reduction in other types of acute diarrhea. These numbers reflect a protective effect against diarrhea in subjects including both adults and children. In terms of children (age < 18 years), seven out of the 12 trials conducted in a health care setting showed a reduction in acute diarrhea of 57%. There was no significant difference in the protective effect of strains, namely Saccharomyces boulardii, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, and Lactobacillus bulgaricus.^[2]

Probiotics were found to be effective in treating acute, infectious diarrhea in children when a review was completed in 2001, involving > 700 children aged from one to 48 months with acute diarrhea.^[3] A 2002 review showed that Lactobacillus reduced the average duration of acute diarrhea by 0.7 days and stool frequency by 1.6 on the second day of treatment. Dosage was most effective at more than ten billion colony-forming units of Lactobacillus during the first 48 hours of diarrhea.^[4] Moreover, there has been evidence showing that probiotics can prevent children and infants from gastroenteritis (also known as stomach flu), which may also cause diarrhea to occur.^[3]

Antibiotic-associated diarrhea

Pseudomembranous colitis.

This illness can generally be accounted for by Clostridium difficile, a bacterium that can sometimes cause severe diarrhea known as pseudomembranous colitis.^[5] In a review of six trials related to antibiotic-associated diarrhea in 766 children aged one month to six years, there was an overall reduction in AAD when children were fed probiotics. The reduction, when compared to placebo, was seen to be from 28.5% to 11.9%; in fact, when patients were fed probiotics along with their dose of antibiotics, one fewer patient would develop AAD out of every seven. Antibiotics fed to the children in the trials included amoxicillin, penicillin and erythromycin. Evidence suggests that S. boulardii is best at preventing AAD in children, Lactobacillus GG ranking second, and a mixture of S. thermophilus and B. lactis relatively ranking last. No conclusion can be made on how probiotics can reduce the risk of AAD from any specific types of antibiotic.^[3]

Novamoxin antibiotic

One of the proposed mechanisms of how probiotics protect from AAD is by regulating the composition of organisms in the intestines. Studies involving L. acidophilus and Bifidobacterium suggest that these microbes inhibit the growth of facultative anaerobic bacteria, which tends to increase during antibiotic treatment. As a result, it is seen that probiotics can alter and prevent changes in the intestinal microflora caused by antibiotics.^[6]

Viral diarrhea

Rotavirus

Viral diarrhea refers to diarrhea caused by a rotavirus, a virus often affecting toddlers and infants. A meta-analysis of nine previously conducted studies has shown that probiotics are also effective in treating viral diarrhea in hospitalized children. Countries of where these studies originated from include Canada, Thailand, and Finland, with subjects ranging from one to above 36 months old. On average, the duration of the illness was shortened by 0.7 days when placing the children on Lactobacillus therapy. Although it is still largely unknown as to how probiotics do this, two mechanisms have been currently proposed. The first mechanism suggests that Lactobacilli augment the development of intestinal mucins (glyosylated proteins), which consequently protect the body from intestinal infections.

Persistent diarrhea

A 2013 review suggested probiotics are effective in treating persistent diarrhea in children, though more research is needed. Persistent diarrhea is an episode that starts acutely but then lasts for 14 days or more; In developing countries it is an important cause of morbidity and mortality in children under five years old. The study showed average duration reduced by four days and shorter hospital stay; stool frequency was reduced on the fifth day.^[7]

Allergy

Atopic eczema.

Probiotics are commonly given to breast-feeding mothers and their young children to prevent eczema, but some doubt exists over the strength of evidence supporting this practice.^[8]

Safety

"Documented correlations between systemic infections and probiotic consumption are few and all occurred in patients with underlying medical conditions."^[9] Rarely, consumption of probiotics may cause bacteremia, fungemia and sepsis in children with lowered immune systems who are already critically ill.^[10] There are no adverse effects from Lactobacillus ingestion.^[7]

References

External links

• A.S.P.E.N.
• Guidelines for the Evaluation of Probiotics in Food, 2002