News
Archive
12.06.2009
Probiotics for the Treatmen...
09.07.2007
New Technical Sales Manager...
14.02.2007
New Appointments at Probiotics
23.11.2006
Effects of probiotics on th...
23.11.2006
Lactase activity of probiot...
23.11.2006
Probiotics and Candida Infe...
23.11.2006
Probiotics and Inflammatory...
23.11.2006
Probiotics for Allergies an...
23.11.2006
Probiotics for the Treatmen...
23.11.2006
Irritable Bowel Syndrome an...
23.11.2006
Probiotic Indication Table
|
Probiotics for the Treatment and Prevention of DiarrhoeaProbiotics for the Treatment and Prevention of Diarrhoea
Introduction
Probiotics represent a nutritional live microbial supplement that positively affects the host by enhancing the microbial balance. They work in a number of ways including; competitive exclusion, production of bacteriocins and lowering of gut pH. Although all probiotics mechanisms of action are not yet fully understood, it is known that they also have an effect on immune responses in the gut, which reduces inflammation.(34) The use of probiotics has been suggested for the prevention and treatment of gut health problems, including acute infectious diarrhoea, antibiotic associated diarrhoea and inflammatory bowel disease. Diarrhoea causes an imbalance in the gut microflora, increased gut permeability and inflammation of the intestine.(36) If probiotic bacteria are able to adhere to the intestinal epithelium and colonise the gut, then it has been suggested they can be used to help treat or prevent diarrhoea.
There are multiple studies suggesting that probiotics are effective for the treatment and prevention of acute non-bloody infectious diarrhoea and antibiotic associated diarrhoea. (11) The mechanisms of action have been studied and one method is thought to be due to the probiotic bacteria interfering with the invasion and adhesion of pathogens.(13) In addition to stopping bacteria infecting cells already exposed, probiotic bacteria may help to protect the gut epithelium from further invasion. Lactobacillus rhamnosus has been shown to have beneficial effects on intestinal immunity, by increasing the numbers of cells that secrete immunoglobulins in the intestinal mucosa and stimulating the local release of interferon. (4) Lactobacillus rhamnosus has also been shown to produce an antimicrobial substance that inhibits the growth of Escherichia coli, Streptococci, Clostridium difficile, Bacteroides fragilis and Salmonella spp.(5)
To summarise the following mechanisms of action have been documented for probiotics:
• Immunomodulation
o Increases the number of intestinal mucosa cells secreting immunoglobulins
o Facilitates antigen transport to underlying lymphoid cells ensuring a faster immune reaction to disease causing bacteria
• Antibacterial action
o Production of antibacterial substances
o Action against common pathogens including Escherichia coli, Clostridium difficile and Salmonella spp.
• Competitive Exclusion
o Good adhesion to the gut wall, preventing pathogens binding
o Colonisation of the gut with beneficial bacteria
Types of Probiotic
The most commonly used probiotic bacteria are Lactobacilli, Bifidobacteria and other lactic acid bacteria, which are species naturally found in the gut. Specific yeast strains are also sometimes used as probiotics and on an experimental basis other organisms, not normally part of the microflora, have been used. Probiotic preparations may contain one bacteria, referred to as monostrain or a number of different bacteria. If the bacteria are all from the same species eg. a blend of Lactobacillus bulgaricus and Lactobacillus casei, but are different strains they are known as multistrain probiotics. However, if the product contains Bifidobacterium longum, Lactobacillus acidophilus and Streptococcus thermophilus, which are different species of bacteria then it would be called a multispecies probiotic.
A literature review compared the functionality and efficacy of monostrain, multistrain and multispecies probiotics.(15) It was found that multispecies probiotics were superior in treating antibiotic associated diarrhoea in children. It is thought that many probiotic bacteria work synergistically within the gut enhancing the beneficial effect. For example different species of probiotic bacteria may be better able to colonise different parts of the gut, produce antibacterial agents against different pathogens or promote an immune response. A study on viral gastroenteritis found that multispecies or multistrain probiotic preparations were able to adhere to the gut during an episode of diarrhoea better than single strain probiotics.(28)
Probiotic products used in human health care:
• Commonly contain Lactobacillus spp., Bifidobacteria spp. and other lactic acid bacteria
• Have different properties and can have synergistic effects
• Can contain multistrain and multispecies probiotics, which have been found to be most effective for diarrhoea
Childhood Diarrhoea
Diarrhoea is common among children and accounts for substantial amounts of disease and even death worldwide. In the developing world, children may be particularly susceptible due to malnutrition, impaired immune status or frequent exposure to pathogens. However, infectious diarrhoea as well as antibiotic associated diarrhoea is common in children throughout the world. Young children (under three years of age) are more susceptible to clinical consequences of infectious diarrhoea and may have the most to gain from probiotic treatment.
A recent review of nine studies using Lactobacillus spp. found that treatment with this probiotic reduced the duration of diarrhoeal episodes by an average of 0.7 days and reduced stool frequency by an average of 1.6 days.(1) It was also noted that some studies showed a reduction in vomiting in those children given Lactobacillus spp. The researchers therefore concluded that Lactobacillus spp is a safe and effective treatment for children with acute infectious diarrhoea. In the review children given probiotics were all hospital in-patients, in developed countries and received oral rehydration therapy in addition to probiotics. This treatment was effective in cases where the children had infectious diarrhoea caused by rotavirus as well as bacterial pathogens.
Patients with diarrhoea are often given a rehydrating solution to drink as part of their treatment in order to prevent dehydration due to loss of fluid in diarrhoea. Probiotics can be easily and effectively added to rehydration preparations and given to patients in the normal way. A literature review found that on average fewer patients taking probiotics had diarrhoea on the third day after their symptoms started and that the treatment reduced the duration of the diarrhoea by 30.48 hours.(18) The researchers therefore concluded that probiotics are a useful addition to rehydration therapy in treating acute infectious diarrhoea in both adults and children.
A multicenter European trial aimed to evaluate the role of Lactobacillus rhamnosus administered with oral rehydration therapy, on non-rotaviral diarrhoea.(31) It was concluded that this kind of treatment for acute diarrhoea results in shorter duration of diarrhoea and faster discharge from hospital. Using the same administration route a trial in Italy looked at the treatment of diarrhoea via family paediatricians.(35) The duration of diarrhoea was recorded for one hundred children, which was reduced from six to three days in children receiving Lactobacillus rhamnosus.
Rotavirus
Rotavirus is a common cause of diarrhoea amongst children in developing countries. Several Lactobacillus species have been tested and an effect shown against rotavirus associated diarrhoea.
Rotavirus often causes gastro enteritis in hospitalised children but can also cause milder diarrhoea in children who are cared for in day care centres or similar institutions. Researchers in Denmark studied the effect of Lactobacillus rhamnosus and Lactobacillus reuteri on acute diarrhoea in children in day care centres.(24) They found that on average those receiving the probiotic had diarrhoea which lasted 40 hours less than those who received the placebo. Interestingly they also found that those children who received the probiotic less than 60 hours after their diarrhoea had started had a more pronounced response to the treatment and that the time to recovery was 79 hours compared to 139 hours, for those who received probiotics later. A similar study with children in a residential home supplemented milk formula with either Bifidobacterium spp. alone or with Streptococcus thermophilus to prevent rotavirus infection.(30) Those infants who received either probiotic supplementation for 8 months showed no signs of rotavirus infection, whereas 30.4% of the controls had indications of infection.
Lactobacillus rhamnosus and Lactobacillus reuteri were given to children who had been hospitalised for acute rotavirus associated diarrhoea.(25) The result was an improvement in their condition and a reduction in the time the virus was excreted. This had the effect of reducing their stay in hospital, particularly if they started probiotic treatment early in the diarrhoeal phase. A review of similar studies on the effects of probiotics on diarrhoea caused by rotavirus in infants and children also found evidence of a clinically significant benefit of probiotics in the treatment of this acute infection.(26)
In summary research into the use of probiotics in childhood diarrhoea has concluded that:
• Probiotics are a safe and effective treatment for children with diarrhoea
• Probiotics can be added to rehydration preparations
• Probiotics reduce the duration of diarrhoea and speed recovery
• Probiotic treatment can reduce time spent in hospital
• Probiotics are effective in treatment diarrhoea caused by bacteria pathogens and Rotavirus
• Probiotics have the greatest effect if given as soon after the onset of diarrhoea as possible
Prevention of Infectious Diarrhoea
Infectious diarrhoea occurs more commonly where children have a poor immune status due to inadequate nutrition or exposure to pathogens. Probiotics could therefore be useful for improving immunity and preventing infectious diarrhoea. This would then have the benefit of preventing hospitalisation or reducing outpatient treatment. In cases where diarrhoea is contacted whilst children are in hospital for another reason, probiotics could help to prevent secondary infections and reduce their length of stay.
Certain Lactobacillus and Bifidobacteria species have been shown to reduce the risk of diarrhoeal disease in high risk population groups in both hospital and home environments.(6-8) A study in undernourished Peruvian children used Lactobacillus rhamnosus to help control diarrhoea, those receiving the probiotic had significantly fewer episodes of diarrhoea over a fifteen month period.(33) There was an even greater decrease in diarrhoeal episodes in younger infants who were not breast fed.
Probiotics can also help to reduce the risk of catching viral gastroenteritis. (2) As well as rotavirus being a cause of hospitalisation in children it is also often found to cause gastroenteritis in those admitted for other reasons. A Polish study showed that the use of Lactobacillus rhamnosus significantly reduced the risk of rotavirus gastroenteritis. Only 6.7% of patients given the probiotic had diarrhoea compared to 33.3% of the controls.(27) Even during episodes of diarrhoea probiotic strains of bacteria showed good adhesion in the gut, therefore helping to maintain the beneficial gut flora during the infection and aiding recovery.(28)
Breast fed babies have Bifidobacteria as the prevalent species in their colonic flora, which is thought to offer some protection against diarrhoea. A trial in France added a Bifidobacterium to a milk formula, which was given to babies under 8 months of age, who were in residential care where they were unable to receive any of the nutritional benefits of breast milk.(20) The incidence of diarrhoea in these infants was 28.3% in the probiotic supplemented group compared to 38.7% in the control, there was also a trend for shorter episodes of diarrhoea in those receiving the bifidobacterium.
The benefits of using probiotics to prevent infectious diarrhoea are:
• Preventing hospitalisation
• Reducing outpatient treatment for diarrhoea
• Protecting malnourished or immunocompromised children
• Reducing infection with pathogenic bacteria and viruses
• Improving the microflora of infants who are not breast fed
• Can be easily and effectively added to milk formula
• Preventing secondary infection in hospitals
• Reducing the transmission of infection in children cared for in a group setting
Antibiotic associated diarrhoea
Twenty percent of people who take a course of antibiotics suffer from diarrhoea. As well as being an unpleasant side effect, it can in some cases, lead to chronic or persistent diarrhoea. Antibiotics are taken for a variety of bacterial infection in order to kill the bacteria and prevent disease. However, as the same time as killing pathogenic bacteria they may also kill the beneficial bacteria within the gut. This effect will vary depending on the type of antibiotic used as well as differences in patients.
A reduction in the number of beneficial bacteria in the gut causes an imbalance in the microflora and can allow pathogenic species to increase. The gastrointestinal microflora is less able to resist colonisation by pathogenic species, which causes clinical symptoms, most commonly diarrhoea. The severity of antibiotic associated diarrhoea may range from a brief episode of diarrhoea to a more serious condition with symptoms such as electrolyte disturbances, dehydration, cramping abdominal pain and toxicity. Probiotics are used to treat or prevent antibiotic associated diarrhoea because they replace the beneficial bacteria which are lost during antibiotic therapy. This in turn helps to prevent colonisation of pathogens, which can cause diarrhoea. Other methods by which probiotics reduce diarrhoea are thought to be due to the production of antimicrobial substances, competition for nutrients and stimulation of intestinal immune responses.
Diarrhoea is a common complication of antibiotic therapy given to children, especially if broad-spectrum agents are used. Lactobacillus rhamnosus has been shown to reduce the risk of antibiotic associated diarrhoea by approximately 75% in children.(9) The same probiotic bacteria was used in an American trial using outpatients receiving antibiotics for various acute infections.(32) They similarly found a significant reduction in stool frequency and increased stool consistency in children receiving probiotics compared with the placebo group. In another study children being treated for respiratory infections with antibiotics, were given either a placebo or Lactobacillus rhamnosus during the course of medication. The incidence of diarrhoea was 5% in the Lactobacillus group and 16% in the placebo group.(10) Another study in children found that those patients who received a probiotic along with a broad spectrum antibiotic had forty three percent fewer diarrhoeal episodes, than those who did not.(23) A meta-analysis of studies on antibiotic diarrhoea concluded that probiotics, particularly Lactobacilli species, could be used to prevent this condition. (3)
Clostridium difficile
It is estimated that 25% of cases of antibiotic associated diarrhoea are caused by Clostridium difficile. Infection with this pathogen can lead to colitis and is a common complication of antibiotic therapy. This problem is becoming increasingly prevalent in hospital inpatients, particularly the elderly. Probiotics have been shown to prevent Clostridium difficile infection, after the use of antibiotics. The probiotic strain Lactobacillus rhamnosus has been used in the prevention of relapsing Clostridium difficile diarrhoea, associated with antibiotic use.
In a trial, elderly patients receiving antibiotics were also given either a placebo or a probiotic containing Lactobacillus and bifidobacterium.(12) Stool samples from all patients were analysed for Clostridium difficle toxins, which were found in 78% of the control group and 46% of the probiotic group. This means that the probiotic was reducing the numbers of this pathogen and the production of toxins. It is these toxins which cause inflammation within the gut, leading to colitis. A review of studies using a probiotic yeast Saccharomyces boulardii also concluded that it was also a safe effective preventative for this major side effect of antibiotics.(29)
Chronic and persistent diarrhoea
Clostridium difficile is a significant cause of chronic persistent diarrhoea and often follows an episode of antibiotic associated diarrhoea.(37) It appears that this bacterium overgrows in the gut of some people and has to be regularly treated with antibiotics. Symptoms of antibiotic associated diarrhoea range from mild or moderate diarrhoea to severe diarrhoea along with fever, vomiting and abdominal pain. Probiotic bacteria able to colonise the gut may help to exclude pathogens by competition as well as by the production of antimicrobial substances. In the case of Clostridium difficile, certain probiotics may also be able to reduce the effects of toxins produced by this bacterium.
Diarrhoea is common in oncology and a small trial showed that probiotics may offer a way to bring about resolution in antibiotic associated chronic diarrhoea.(17) Children can also experience persistent diarrhoea due to enteric bacteria pathogens or rotavirus. The efficacy of Lactobacillus casei and Lactobacillus acidophillus, compared to Saccharomyces boulardii and a placebo, against persistent diarrhoea in children was evaluated.(22) It was found that both probiotic treatment significantly reduced both the number of stools being passed and the duration of diarrhoea, as well as reducing vomiting. It was therefore concluded that probiotics were a useful tool in the management of persistent diarrhoea in children.
Research into antibiotic associated diarrhoea found that:
• 20% of people who take antibiotics get diarrhoea
• 25% of cases are caused by Clostridium difficle
• Antibiotic therapy kills beneficial as well as pathogenic bacteria
• Antibiotics strip the gut of protective microflora and causing an imbalance
• The incidence of antibiotic associated diarrhoea depends on the antibiotic used and each individual's risk factors.
• Probiotics will replace beneficial bacteria
• Probiotic bacteria will help prevent colonisation of pathogens
• Probiotics have been shown to be effective at preventing antibiotic associated diarrhoea
• Patients at risk of developing antibiotic-associated diarrhoea would benefit from taking probiotics at the same time
• They are particularly useful in cases of Clostridium difficle to prevent colitis
• Probiotics can prevent colonisation by Clostridium difficle and reduce the effect of the toxins they produce
• Probiotics can be used to prevent chronic diarrhoea caused by Clostridium difficle
• Probiotics are a useful for the management of persistent diarrhoea in children
Travellers Diarrhoea
Travellers diarrhoea is the most common health problem for people who travel, with 20-50% of them affected.(38) People travelling to high risk areas, such as developing countries are particularly likely to develop acute diarrhoea. The most common agents of infection are; Escherichia coli, Salmonella spp., Shigella spp., Campylobacter spp. and non cholera vibrios. People with travellers' diarrhoea do not normally require treatment and recover within a week. The main problem with this condition is inconvenience, with travellers missing days of their holiday or business trip. However, for infants, the elderly or those with serious health conditions there may be more severe consequences. These people may require hospital treatment, take longer to recover and have further complications.
It has been suggested that taking antibiotics preventitaively could help people who are at the greatest risk from travellers' diarrhoea. However, there may be problems with side effects and targeting the right microorganism, as well as concern about the emergence of bacteria resistant to antibiotics.(39) The usual advise for travellers is to avoid high-risk foods and drink bottled water but this is sometime difficult to adhere to and may not always be effective.(40) The use of rehydration products is also important if diarrhoea does develop.
The use of probiotics as a preventative for diarrhoea whilst travelling has been studied and there is evidence which suggests a lower incidence of diarrhoea when Lactobacilli and Bifidobacterium are used both as prophylactics and for treatment. A study using tourists visiting Turkey found an 11.8% decrease in the incidence of diarrhoea in those who took Lactobacillus rhamnosus.(41) A similar study gave the same probiotics strains to American tourists visiting Mexico and found a benefit in preventing diarrhoea.(42) It has been suggested that in order to get the greatest protection from diarrhoea, traveller's should start taking probiotics before any trip, during travel and continue afterwards. This allows the establishment of beneficial bacteria within the gut prior to travel and helps to ensure optimum natural immunity.
Travellers could benefit from taking probiotics:
• Up to half of people who travel experience diarrhoea
• This can be serious for people in high risk categories
• Probiotics can help to prevent diarrhoea
• Travellers should take probiotics before, during and after their trip
Benefit of Prebiotics
Prebiotics are non-digestible food ingredients that are used preferentially by beneficial bacteria as a food source. This in turn selectively increases the growth and or activity of particular bacteria within the colon. In other words prebiotics are food for the beneficial bacteria within the gut, in this way they complement probiotic bacteria and strengthen their effect. Products containing both probiotics and prebiotics are called synbiotics due to the synergistic effect these ingredients have within the gut.
A trial introducing Bifidobacterium lactis and the prebiotic, galacto-oligosaccharide to milk for young children found that there was a significant reduction in bloody diarrhoea and a non significant 10% reduction in all diarrhoea.(16) In another study children receiving antibiotic treatment were given a nutritional supplement with or without a synbiotic.(19) The patients who received the synbiotic with their medication gained more weight and had significantly less bacterial illness after 14 days.
Benefits have also been found using probiotics and prebiotics, to prevent antibiotics associated diarrhoea in children. An Italian trial found that when FOS (fructooligosaccharide) and Lactobacillus sporogens were given at the same time as antibiotic therapy only 38% of patients had diarrhoea compared to 71% of the children who received a placebo.(21) There was also a significant reduction in the duration of the diarrhoea in those children who received the synbiotic, 0.7 compared to 1.6 days. Synbiotics are thought to shorten the course of diarrhoea by promoting a rapid improvement in stool formation and reduction stool frequency.
Synbiotic preparations have many benefits in the prevention and treatment of diarrhoea:
• Prebiotics are a food source for beneficial bacteria
• Prebiotics enhance the effects of probiotics
• Synbiotics are effective in preventing infectious diarrhoea
• Synbiotics can also be used to prevent antibiotic associated diarrhoea
• Synbiotics have been shown to reduce the duration of diarrhoea
• Synbiotics improve stool formation and reduce stool frequency
Conclusion
The use of probiotics has been studied for the treatment and prevention of diarrhoea with a variety of causes;
• For treatment of diarrhoea probiotics work well if added to oral rehydration solutions.
• Probiotics can be used in the treatment of diarrhoea caused by bacteria and rotavirus
• Probiotics are also effective in the prevention of acute infectious diarrhoea
• If taken at the same time as antibiotic therapy probiotics are effective as a preventative for antibiotic associated diarrhoea
• Probiotics are useful in the control of diarrhoea caused by Clostridium difficle
• Those who suffer from chronic or persistent diarrhoea may benefit from taking probiotics to reduce symptoms
• People who travel, particularly to high risk countries, could take probiotics to prevent diarrhoea
• Multistrain and multispecies probiotics offer more mechanisms of action within the gut and have been shown to be more effective at treating diarrhoea
• Prebiotics work well in combination with probiotics to reduce diarrhoea.
Research trials suggest that probiotics offer a safe and effective treatment for children and adults with acute infectious disease. Documented beneficial effects of probiotics on diarrhoea include:
• Reduces duration of diarrhoeal episodes
• Reduces stool frequency
• Reduces vomiting
• Reduces risk of diarrhoea
• Faster discharge from hospital
• Shorter recovery time
• Reduces period of pathogen excretion
References
1. Van Niel CW, Feudtner C, Garrison MM, Dimitri A (2002). Lactobacillus Therapy for acute Infectious Diarrhoea in Children: A Meta-analysis. Pediatrics. 109(4):678-684.
2. Vanderhoof JA and Young RJ (2002). Probiotics in Peadiatrics. Pediatrics. 109:956-958.
3. D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ (2002). Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ. 324:1361.
4. Benno Y, et al. (1996). Effects of Lactobacillus GG yoghurt on human intestinal micro-ecology in Japanese subjects. Nutr Today. 31(6 suppl):9-11S.
5. Gorbach SL (1996) The discovery of Lactobacillus GG. Nutr Today. 31(6 suppl):2-4S
6. Guandalini S, Pensabene L, Zikri MA, Dias JA, Casali LG, Hoekstra H, Kolacek S, Massar K, Micetic-Turk D, Papadopoulou A, de Sousa JS, Sandhu B, Szajewska H, Weizman Z (2000). Lactobacillus GG administered in oral rehydration solution to children with acute diarrhoea – a multicenter European trial. J Pediatr Gastroenterol Nutr. 30:54-60
7. Szajewska H, Kotowska M, Mrukowicz JZ, Armanska M, Mikolajczyk W (2001). Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr. 138:361-365
8. Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH (1994). Feeding of Bifidobacterium and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet. 344:1046-1049
9. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ (1999). Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr. 135:564-568
10. Arvola T, Laiho K, Torkkeli S, Mykkanen H, Salminen S, Maunula L, Isolauri E (1999). Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhoea in children with respiratory infections – a randomized study. Pediatrics. 104(5)
11. Shaoul R and Bamberger E (2004). An update on probiotics and prebiotics in children
Harefuah. 143(5):377-81, 389
12. Plummer S, Weaver MA, Harris JC, Dee P, Hunter J (2004). Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Int Microbiol. 7(1):59-62.
13. Resta-Lenert S and Barrett KE (2003). Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut. 52(7):988-97.
14. Goossens D, Jonkers D, Stobberingh E, van den Bogaard A, Russel M and Stockbrugger R (2003). Probiotics in gastroenterology: indications and future perspectives. Scand J Gastroenterol Suppl. 239:15-23.
15. Timmerman HM, Koning CJ, Mulder L, Rombouts FM, Beynen AC (2004). Monostrain, multistrain and multispecies probiotics -A comparison of functionality and efficacy. Int J Food Microbiol. 96(3):219-33.
16. Sazawal S, Dhingra U, Sarkar A, Dhingra P, Deb S, Marwah D, Menon VP, Kumar J, Black RE (2004). Efficacy of milk fortified with a probiotic Bifidobacterium lactis (DR-10TM) and prebiotic galacto-oligosaccharides in prevention of morbidity and on nutritional status. Asia Pac J Clin Nutr. 13(Suppl):S28.
17. Benchimol EI and Mack DR (2004). Probiotics in relapsing and chronic diarrhea. J Pediatr Hematol Oncol. 26(8):515-7.
18. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF (2004). Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2:CD003048.
19. Schrezenmeir J, Heller K, McCue M, Llamas C, Lam W, Burow H, Kindling-Rohracker M, Fischer W, Sengespeik HC, Comer GM, Alarcon P (2004). Benefits of oral supplementation with and without synbiotics in young children with acute bacterial infections. Clin Pediatr (Phila). 43(3):239-49.
20. Chouraqui JP, Van Egroo LD, Fichot MC (2004). Acidified milk formula supplemented with bifidobacterium lactis: impact on infant diarrhea in residential care settings. J Pediatr Gastroenterol Nutr. 38(3):288-92.
21. La Rosa M, Bottaro G, Gulino N, Gambuzza F, Di Forti F, Ini G, Tornambe E (2003). Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children. A multicentric double-blind vs placebo study. Minerva Pediatr. 55(5):447-52.
22. Gaon D, Garcia H, Winter L, Rodriguez N, Quintas R, Gonzalez SN, Oliver G (2003). Effect of Lactobacillus strains and Saccharomyces boulardii on persistent diarrhea in children. Medicina (B Aires). 63(4):293-8.
23. Jirapinyo P, Densupsoontorn N, Thamonsiri N, Wongarn R (2002). Prevention of antibiotic-associated diarrhea in infants by probiotics. J Med Assoc Thai. 85 Suppl 2:S739-42.
24. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Moller PL, Tvede M, Weyrehter H, Valerius NH, Paerregaard A (2002). Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J. 21(5):417-9.
25. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Moller PL, Pedersen P, Tvede M, Weyrehter H, Valerius NH, Paerregaard A (2002). Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J. 21(5):411-6.
26. Szajewska H and Mrukowicz JZ (2001). Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr. 33 Suppl 2:S17-25.
27. Szajewska H, Kotowska M, Mrukowicz JZ, Armanska M, Mikolajczyk WJ (2001). Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. Pediatr. 138(3):361-5.
28. Juntunen M, Kirjavainen PV, Ouwehand AC, Salminen SJ, Isolauri E (2001). Adherence of probiotic bacteria to human intestinal mucus in healthy infants and during rotavirus infection. Clin Diagn Lab Immunol. 8(2):293-6.
29. Bergogne-Berezin E (2000). Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents. 16(4):521-6.
30. Phuapradit P, Varavithya W, Vathanophas K, Sangchai R, Podhipak A, Suthutvoravut U, Nopchinda S, Chantraruksa V, Haschke F (1999). Reduction of rotavirus infection in children receiving bifidobacteria-supplemented formula. J Med Assoc Thai. 82 Suppl 1:S43-8.
31. Guandalini S, Pensabene L, Zikri MA, Dias JA, Casali LG, Hoekstra H, Kolacek S, Massar K, Micetic-Turk D, Papadopoulou A, de Sousa JS, Sandhu B, Szajewska H, Weizman Z (2000). Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial. J Pediatr Gastroenterol Nutr. 30(1):54-60.
32. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ (1999). Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr. 135(5):564-8.
33. Oberhelman RA, Gilman RH, Sheen P, Taylor DN, Black RE, Cabrera L, Lescano AG, Meza R, Madico G (1999). A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr. 134(1):15-20.
34. D'Angelo G, Angeletti C, Catassi C, Coppa GV (1998). Probiotics in childhood. Minerva Pediatr. 50(5):163-73.
35. Guarino A, Canani RB, Spagnuolo MI, Albano F, Di Benedetto L (1997). Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr. 25(5):516-9.
36. Salminen S, Isolauri E, Salminen E (1996). Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful strains and future challenges. Antonie Van Leeuwenhoek.
70(2-4):347-58.
37. Dowhower Karpa K (2003). Bacteria for Breakfast. Trafford Publishing.
38. Castelli F, Beltrame A, Carosi G (1998). Principles and management of the ambulatory treatment of traveller's diarrhea Bull Soc Pathol Exot. 91(5 Pt 1-2):452-5.
39. Farthing MJ (1991). Review article: prevention and treatment of travellers' diarrhoea. Aliment Pharmacol Ther. Feb;5(1):15-30.
40. Al-Abri SS and Beeching NJ (2005). Traveller's diarrhoea. The Lancet Infectious Diseases. 5:6
41. Oksanen PJ, Salminen S, Saxelin M, Hamalainen P, Ihantola-Vormisto A, Muurasniemi-Isoviita L, Nikkari S, Oksanen T, Porsti I, Salminen E, et al. (1990). Prevention of travellers' diarrhoea by Lactobacillus GG. Ann Med. 22(1):53-6.
42. Hilton E, Kolakowski P, Singer C, Smith MJ (1997). Efficacy of Lactobacillus GG as a Diarrheal Preventive in Travelers.Travel Med. 4(1):41-43.
|
