Abstract
Infectious gastroenteritis continues to be a leading cause of mortality and morbidity worldwide. The cornerstone of treatment remains replacement of water and electrolyte losses with oral rehydration solution. Until a few years ago, probiotics were discussed primarily in the context of alternative medicine, but they are now entering mainstream medical practice since a decrease of the severity and duration of infectious gastroenteritis in approximately 24 hours has been shown for some strains. Therefore, probiotics are a potential add-on therapy in acute gastro-enteritis. The shortening of the duration of diarrhoea and the reduction in hospital stay result in a social and economic benefit. Evidence found in viral gastroenteritis is more convincing than in bacterial or parasitic infection. Mechanisms of action are strain specific and only those commercial products for which there is evidence of clinical efficacy should be recommended. Timing of administration is also of importance. In acute gastroenteritis, there is evidence for efficacy of some strains of lactobacilli (e.g. Lactobacillus caseii GG and Lactobacillus reuteri) and for Saccharomyces boulardii. Probiotics are “generally regarded as safe”, but side effects such as septicaemia and fungaemia have very rarely been reported in high-risk situations. Although most studies conclude in a statistically significant shortening of the duration of diarrhea, the clinical relevance of this finding is limited. In conclusion, selected strains of probiotics result in a statistically significant but clinically moderate benefit in shortening the duration of diarrhoea caused by acute infectious gastroenteritis.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Acute infectious gastroenteritis remains the most common cause of diarrhoea worldwide and is a leading cause of death in childhood. Despite improvements in public health and economic wealth, the incidence of intestinal infections remains high in the developed world and continues to be an important clinical problem with relevant morbidity [10]. The risk of diarrhoeal disease is increased in selected groups including young infants, immune deficient individuals (HIV, cancer, chemotherapy, malnutrition), and people with a high exposure to pathogens (informal settlements, travellers, contaminated food, and medications buffering gastric acid), etc.
More than 2000 years ago, the Roman author Plinius The Old recommended fermented milk in the treatment of acute gastroenteritis. The term “probiotics” (meaning “for life”) was not used until the 1960s. However, the healthy effects of certain bacteria have been noted for more than a century [38]. As early as in 1906, Tissier noted that a significant stool colonization with bifidobacteria was protective against the likelihood of the development of diarrhoea in children [68]. Probiotics are non-pathogenic live micro-organisms that resist normal digestion to reach the colon alive, which, when consumed in adequate amounts, have a positive effect on the health of the host. Probiotics are marketed in several countries and widely used by paediatric health care providers [44]. The number of publications on probiotics in different diseases and conditions has literally exploded during recent years, especially in the area of acute infectious gastroenteritis. However, it is well known by opinion leaders that many negative reports remain unpublished.
The commercialised products
One of the major problems in this issue regards the (lack of) quality control of commercialised products. There are a multitude of foods and food-supplements that contain micro-organisms. Fermented alimentation features in most traditional cuisines. The food industry includes selected micro-organisms in food, primarily in milk-drinks or yogurts. Most probiotics in capsules are commercialised as food-supplements. After identification of the isolates using whole-cell protein profiling, wrong labelling was noted in 47% of the food supplements and 40% of the dairy products [66]. Mislabelling of food supplements is a worldwide problem [20]. As a consequence, it is impossible for the consumer and very difficult for the prescriber to separate food supplements among those with “good” from those with “poor” quality. In contrast, a biotherapeutic agent is a probiotic with proven therapeutic efficacy, and thus considered as medication. The legislation of food-supplements differs from that of medication. As a consequence, biotherapeutics are subject to a more stringent regulation and quality control than food supplements and dairy products. Fundamental research on the mechanisms of action of specific strains and clinical trials with commercialised products are mandatory. In vitro effects of a strain may display opposite behaviour in vivo [28]. Effects demonstrated for one strain cannot be extrapolated to other strains, even if they belong to the same species. Only these strains and their commercialized “controlled” product for which convincing data are available can be recommended. Since some commercialized products are combinations of different strains, repeated laboratory and clinical testing of every combination of strains is mandatory. Lactobacillus acidophilus LB has been shown to have antibacterial activity against E. coli [4, 15]. However, if the E. coli is present in the gastro-intestinal tract of the host prior to the L. acidophilus LB, as occurs in acute gastroenteritis, its antibacterial activity is strongly reduced by non-specific steric hindrance of the receptor sites [41]. Adherence of Bifidobacteria Bb12 improves in the presence of Lactobacillus casei GG, both in healthy infants and during episodes of diarrhoea, suggesting that synergism may as well occur [31].
Mechanisms of action
Per definition, a probiotic needs to be detectable alive throughout the entire digestive system. Most micro-organisms present in naturally fermented dairy products do not survive contact with gastric acid and bile. Only 1.5% of L. acidophilus and 37.5% of bifidobacteria present in food reach the ileum alive [41]. Probiotics do not colonize the gastro-intestinal tract as they become undetectable a few days after stopping the administration. This results in the absence of any risk for long-term side-effects. More studies are needed on pharmacodynamic and pharmacokinetic aspects, as the number of dose-related efficacy studies are minimal.
Every strain is different. Because the vast majority of probiotic products are commercialized as food supplements or dairy products, scientifically validated information regarding the strains is often limited. However, one lactobacillus does not equal another, as one Saccharomyces does not equal another.
There are many hypothesized mechanisms by which probiotics produce a healthy effect, including competitive inhibition with pathogenic bacteria, effects on barrier function, and effects on immune function [9, 37]. In general, probiotics help to improve the balance of the intestinal microflora. However, yeast probiotic organisms such as Saccharomyces boulardii do not change gastro-intestinal flora [17]. Dietary addition of prebiotic oligosaccharides such as oligofructose enriched inulin, or L. casei Shirota and B. breve result in a favourable effect on the colonic nitrogen metabolism, which in the case of the prebiotic, was accompanied by an increase in total faecal bifidobacteria [18]. Probiotics have an antimicrobial effect through modifying the microflora, secreting antibacterial substances, competing with pathogens to prevent their adhesion, and also competing with nutrients necessary for pathogen survival, producing an antitoxin effect, and reversing some of the consequences of infection on the gut epithelium such as secretory changes and neutrophil migration [43]. It is suggested that probiotic microorganisms compete for receptor sites in the intestinal lumen or compete with pathogens for nutrients [22]. While adherence of a probiotic strain to the gastrointestinal mucosa is reported as one of the major mechanisms of action, most beneficial effects are likely to be immune mediated. S.boulardii is known to influence inflammatory pathways (NF-κB, MAPK) mediated through soluble factors [58]. Other proposed mechanisms include enhancing host immune defenses via strengthening tight junctions between enterocytes, increasing immunoglobin A production, stimulating cytokines and producing substances thought to secondarily act as protective nutrients (arginine, glutamine, short-chain fatty acids) for the gut [19, 22]. The polyamine increase induced by S.boulardii in humans results in a maturation of brush border disaccharidases and enzymes (lactase, sucrase, maltase and aminopeptidase, and an increase in the number of glucose carriers in the enterocyte-membrane) [8].
Since exact denomination of strains is complex, most clinicians are not familiar with this aspect, offering industry the possibility to provide misleading information. Demonstrated mechanisms of action in controlled laboratory conditions may not be reproducible in clinical trials.
Prevention of acute infectious gastroenteritis
Viral pathogens are the major causal organisms for infectious diarrhoea, accounting for up to 70–80% of all episodes. Rotavirus is the most prevalent pathogen and, as a consequence, rotavirus vaccination may to some extent alter the epidemiology of infectious gastroenteritis.
The longer an infant is breastfed and the longer breastfeeding is exclusive, the better the protection from infectious diseases such as gastroenteritis. Promotion of (exclusive) breastfeeding should be maximally endorsed. During recent years, attempts have been made to adapt the composition of second choice infant feeding, cow’s milk based formula, to better mimic the immune development of breastfed infants. To recreate these benefits, probiotics and prebiotic oligosaccharides have been added to infant formula. Saran et al. [51] showed that feeding fermented milk to Indian infants over a period of 6 months resulted in a significantly better weight gain and a 50% reduction of infectious diarrhoea. The preventive beneficial action of probiotic-enriched formula is less obvious in the developed world. While most trials show a positive trend, the latter is not consistent [1]. However, no studies have suggested side-effects of probiotic formula in healthy infants. Data on the prevention of infectious gastroenteritis with prebiotic oligosaccharides are limited to one open-label trial in infants fed for 9 months with a prebiotic enriched formula [7].
More than ten years ago, Saavedra et al. [48] showed that Streptococcus thermophilus and Bifidobacterium bifidum (later renamed B.lactis) prevented nosocomial acquired diarrhoea in a small group of children admitted for long stays to a chronic care institution. A large double-blind randomized study in 220 children did not show a statistically significant protective effect of Lactobacillus GG for nosocomial rotaviral infection [48]. Another more recent study included 90 healthy infants living in residential nurseries or foster care centers and failed to demonstrate a reduction in the prevalence of diarrhoea with the administration of a formula supplemented with the viable B. lactis strain BB12 when compared with placebo (28.3% vs 38.7%; RR 0.7; 95% confidence interval 0.4–1.3) [14]. A formula fermented with B. breve c50 and Str. thermophilus 065 was well accepted and resulted in normal growth of infants [67]. However, incidence, duration of diarrhoea episodes, and number of hospital admissions did not differ significantly between groups. Episodes were less severe in the fermented formula group with fewer cases of dehydration, fewer medical consultations and fewer prescriptions of oral rehydration solutions [67]. Table 1 summarizes a selection of studies on prevention of acute gastroenterities.
Seven children would need to be treated with a probiotic to prevent one patient from developing nosocomial rotaviral gastroenteritis [59]. However, the protective effect on prevention of diarrhoea becomes far less significant if the incidence of diarrhoea (episodes per patient-month) rather than the percentage of patients with diarrhoea is taken into account [60]. Three large, randomized controlled trials provide evidence of a very modest effect (statistically significant, but of questionable clinical importance) of some probiotic strains (Lactobacillus GG, L. reuteri, B. lactis) on the prevention of community-acquired diarrhoea [61]. Today, there is not enough evidence to recommend the routine use of probiotics to prevent nosocomial diarrhea [61].
Traveller’s diarrhoea can be considered as a high-risk situation for infectious gastroenteritis, but the data currently available are not convincing for preventive use of probiotics. At least three placebo-controlled studies with lactobacilli have been performed, all with negative results [25, 32, 45]. One trial with S. boulardii reported a clinically small but statistically significant preventive effect in a specific subgroup, suggesting geographical differences in efficacy [34].
Treatment of infectious gastroenteritis
Treatment of acute infectious gastroenteritis should focus on the pathophysiological consequences of the condition: loss of water and electrolytes and a disturbance of the gastrointestinal ecosystem. Several studies on treatment of acute gastroenteritis can be found in a summary in Table 2. Probiotics address the second pathophysiological aspect of acute gastroenteritis: abnormal gastro-intestinal flora. Bacterial biotherapeutic strains comprise different lactobacilli and bifidobacteria, but to a certain extent also non-pathogenic E. coli (E. coli Nissle 1917) and some strains of enterococci (although relevant transfer of plasmid induced resistance was reported with enterococci). The yeast S. boulardii is the only non-bacterial biotherapeutic strain known.
L. caseii GG compared to placebo reduced significantly the duration of hospitalization in rotavirus diarrhoea (1.4 vs 2.4 days) in 71 children treated with ORS [29]. The efficacy of Lactobacillus GG was confirmed in a study of 40 Pakistani children admitted for severe diarrhoea and malnutrition compared to controls in reducing the duration of non-bloody diarrhoea (31% vs 75% at 48 hours) [47]. Shornikova et al. showed similar results in a trial of 123 hospitalized children (33% with rotavirus and 21% with bacterial diarrhoea) with Lactobacillus GG in reducing the duration of viral diarrhoea (2.7 vs 3.7 days) [55]. The same group assessed the efficacy of L. reuteri in 66 hospitalized children with rotavirus diarrhoea, randomized into 3 groups: placebo in one group and two groups with different doses of L. reuteri (107 and 1010 cfu/g once a day for 5 days). The probiotic reduced the duration of diarrhoea with a dose-dependent effect (2.5 days in the placebo group vs 1.9 and 1.5 in the L. reuteri groups, respectively) [56]. Lactobacillus GG halved the duration of diarrhoea in out-patient children and significantly reduced rotavirus shedding [24]. A multi-center European prospective, randomized controlled trial of 287 children with acute diarrhoea with L. casei GG as an add-on to ORS, showed a significant decrease of the duration of diarrhoea by about 10% (a mean duration of diarrhoea of 123 hours in the placebo group vs 110 hours in the intervention group) [23]. A more detailed analysis showed that the difference was greatest in the rota-positive group (115 vs 136 hours) and that there was no difference in the subgroup with invasive pathogens (about 1/5th of all inclusions; 124 vs 121 hours duration of diarrhoea) [23]. L. acidophilus LB (Lacteol Fort, a product containing heat-killed lactobacilli) was tested in 73 children with acute diarrhoea (50% rotavirus positive) resulting in a similar reduction of duration (43 vs 57 hours) [57]. Comparable results have been recently obtained in a double-blind (DB) RCT involving 87 Polish children with infectious diarrhoea with a mixture of three Lactobacillus rhamnosus strains (573L/1; 573L/2; 573L/3). L. rhamnosus strains significantly shortened the duration of rotavirus diarrhoea (76 +/− 35 h vs 115 +/− 67 h; p = 0.03) but not of diarrhoea of other aetiology. Gut colonization with administered strains was 80% and 41% at 5 and 14 days, respectively. Intervention also shortened the time of intravenous rehydration (15 ± 14 h vs 38 ± 33 h; p = 0.006) although factors such as physician variability may have influenced the outcome [64]. The examined strains were detected in 37/46 (80.43%) patients after 5 days and in 19/46 (41.3%) patients after 14 days after the start of the treatment [65]. L. rhamnosus 573L/1 strain colonized the G.I. tract more persistently [65]. Persistence of colonization is dependent on the properties of administered probiotic strains [65]. However, lactobacilli also failed to shorten the duration of diarrhoea. At least three randomized controlled trials (RCTs) in developing countries negated the beneficial effect of Lactobacillus GG and L .acidophilus in acute diarrhoea, likely related to the distinct aetiological profile [16, 33, 50]. In children with more severe diarrhoea, there was no demonstrable benefit of L. casei GG [16, 50]. Absence of shortening of the duration of diarrhoea was also reported for a mixture of L. acidophilus, B. bifidum (later renamed B. lactis) and L. bulgaricus [35]. L. paracasei strain ST11 did not reduce the volume of stool output in rotavirus infection but improved the outcome of non-rotavirus diarrhoea in children from Bangladesh [52]. Three meta-analyses concluded that the majority of the studies had been performed in the developed world, and that there was efficacy for L. rhamnosus GG, acidophilus and bulgaricus [27, 62, 69]. In particular, the duration of (viral) diarrhoea was significantly reduced (about 17 hours or 0.7 days; relative risk (RR) 0.40 and 4 children need to be treated (NNT) to protect one subject from diarrhoea) compared to controls [62]. The efficacy of Lactobacillus GG appeared related to the logarithm of the dose (>1011 as the most efficient dose) [69]. A Cochrane review examined 23 RCTs and 1,917 participants (1,449 children) and highlighted the beneficial effect of probiotics as an add-on treatment to ORS in reducing the duration of diarrhoea (of about 30 hours with an RR 0.7) without significant side effects in immune-competent subjects [3]. Regarding the other bacterial strains evaluated (Streptococcus thermophilus, L.acidophilus and bulgaricus) more studies are needed [3]. More studies on the mechanisms of action in clinical situations are also needed [3]. Shamir and coworkers showed a reduction in duration of acute gastroenteritis from 1.96 ± 1.24 to 1.43 ± 0.71 days (p = 0.017) with the addition of 109 CFU Streptococcus thermophilus, B. lactis, L. acidophilus, 10 mg zinc and 0.3 gram fructo-oligosaccharides per day [54].
Saccharomyces boulardii is a non pathogenic yeast isolated from the lychee fruit in Indonesia and introduced in France for the treatment of diarrhoea since 1950. The first double-blind, prospective, randomized trials of S. boulardii were performed more than 15 years ago: diarrhoea persisted for more than 7 days in 12% in the placebo group and in 3% in the S. boulardii group [26]. Since then, several double-blind, prospective, randomized trials performed with S. boulardii in children with acute gastro-enteritis have systematically shown a significant improvement in comparison to placebo. A consecutive series of 130 Mexican children, 3 months to 3 years old, with acute infectious diarrhoea were treated with ORS and placebo or S. boulardii (600 mg/d or 1.2 × 1010 CFU/day) for 5 days [13]. A significant decrease in the number of stools was apparent from day 2 onward [13]. After 48 hours, the percentage of children considered cured was almost 50% in the S. boulardii group compared to 8% in the placebo group; on day 4, resolution was up to 95% in the intervention group compared to just almost 50% in the placebo group [13]. Kurugol treated 200 children with acute diarrhoea with 250 mg (or 5 × 109 CFU/day) S. boulardii or placebo for 5 days: duration of both diarrhoea and hospital stay decreased in approximately 24 hours [36]. Villaruel and co-workers showed similar results in ambulatory care in Argentina: diarrhoea persisted for more than 7 days in 27% of a placebo group compared to 7% of a group treated with S. boulardii for 6 days, with a greater effect if treatment was started within the first two days of the disease [70]. S. boulardii improved tolerance of feeding in children with chronic Giardia Lamblia infection [12]. S. boulardii is also effective in amoebiasis and HIV-diarrhoea [40, 49]. A randomized controlled open-label trial in Pakistani children with acute infectious gastroenteritis showed that administration of 500 mg (or 1 × 109 CFU/day) S. boulardii for 5 days significantly reduced the frequency of stools and duration of diarrhoea (3.5 days versus 4.8 days, p = 0.001) and resulted two months later in a 50% decrease in re-infection rates and 30% better weight gain [5]. Szajewska and coworkers recently concluded that S. boulardii has a moderate clinical benefit in otherwise healthy infants and children with acute gastroenteritis, mainly by shortening the duration of diarrhoea [63]. Since most of the studies with S. boulardii have methodological limitations, results should be interpreted with caution [63].
A shortening of the duration of diarrhoea, as well as a reduced hospital stay suggests a relevant social and economic benefit of biotherapeutic treatment in adjunction to ORS in acute infectious gastroenteritis in children.
Numerous clinical trials have been published evaluating different probiotics in the treatment of acute gastroenteritis but vary in relation to strains tested, dosage, methodological quality, diarrhoea definitions and outcomes. Most studies show a statistically significant effect that is of only moderate clinical benefit, with the greatest effect in viral and watery diarrhea [61]. In general, meta-analyses of published trials conclude in a reduction of diarrhoeal duration of approximately 24 hours (17–30 hours) for selected strains of lactobacilli (such as L. casei GG, L. acidophilus, L. Bulgaricus and L. reuteri) and S. boulardii [3, 27, 53, 59, 61, 63, 69]. One should be aware that the available literature is biased since not all negative trials are reported. Greater efficacy has been shown if the probiotic is administered early in the disease. Probiotics in acute diarrhoea of diverse causes reduced the duration in children with about 57% (35–71%) [53]. In general, there is a lack of data from community-based trials and from developing countries, except for S. boulardii. However, some authors stress that business pressures may force usage of probiotics (and antisecretory drugs such as racecadotril) as important in the management of acute diarrhoea while their relevance has yet to be established [2].
Safety and side effects
Probiotics are “generally regarded as safe” and side-effects in ambulatory care are rarely 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% [22]. Invasive infections have been primarily noted to occur in immuno-compromised adults [6]. Lactobacilli have been reported (in adults) to cause cases with sepsis, meningitis and infections localized in different organs [37, 39, 46]. Invasive infections in infants and children are exceedingly rare [6]. Two cases of bacteriaemia attributable to lactobacillus supplementation, with identical molecular clinical and supplement isolates, were recently reported in an infant and a child without underlying gastrointestinal disease or immunocompromised status [9]. Sepsis with probiotic lactobacilli has been reported in children with short gut. Probiotic enterococci may be of higher risk given possible plasmid transfer in immunocompromised patients. Fungaemia with S. boulardii has been reported in about 50 patients [21]. A central venous catheter is the main risk factor [21]. Fungaemia has even been reported in patients with deep central venous lines hospitalized in a bed next to a patient treated with the yeast [11]. Translocation from the gastro-intestinal tract in the systemic circulation has not been reported. These case reports 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 [9]. The potential benefits of supplementation should be weighed against the risk of development of an invasive infection resulting from probiotic therapy.
In order to minimize the risk for side-effects such as fungaemia and bacteriaemia, more research should be done with inactivated or non-viable preparations. These modified probiotic preparations may be the preferred product in at-risk situations. It may not be necessary to administer the intact probiotoc organisms to achieve benefits. At the basic research level, products of probiotics such as secreted proteins or DNA can block inflammation and stop the death of epithelial cells [30].
Conclusion
Although probiotics can be helpful for specific disorders, they have been broadly prescribed for disorders without clear evidence to support their use [44]. Rapid rehydration and realimentation remain the cornerstone of the treatment of acute gastroenteritis [2]. Biotherapeutic agents administered as add-on medication are likely to decrease the duration of acute infectious gastroenteritis in about 24 hours. Furthermore, with S.boulardii, a 24-hour reduction in hospital stay has been documented. Literature shows a statistically significant but clinically moderate benefit for some strains, mainly in infants and young children, in the treatment of acute watery diarrhoea, especially in rotavirus gastroenteritis. Not all negative trials are published. Both for lactobacilli and S. boulardii greater efficacy has been shown if the treatment is started early. Because of strain-specificity, only those organisms that have been clinically tested can be recommended—L. casei GG and S.boulardii being the most reported.
References
Agostoni C, Axelsson I, Braegger C, Goulet O, Koletzko B, Michaelsen KF, Rigo J, Shamir R, Szajewska H, Turck D, Weaver LT, ESPGHAN Committee on Nutrition (2004) Probiotic bacteria in dietetic products for infants: A commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 38:365–374
Alam S, Bhatnagar S (2006) Current status of anti-diarrheal and anti-secretory drugs in the management of acute childhood diarrhea. Indian J Pediatr 73:693–696
Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF (2004) Probiotics for treating infectious diarrhea. Cochrane Database Syst Rev 2:CD003048
Bernet MF, Brassart D, Neeser JR, Servin AL (1994) Lactobacillus acidophilus LA 1 binds to cultured human intestinal cell lines and inhibits cell attachment and cell invasion by enterovirulent bacteria. Gut 35:483–488
Billoo AG, Memon MA, Khaskheli SA, Murtaza G, Iqbal K, Saeed Shekhani M, Siddiqi A (2006) Role of a probiotics (Saccharomyces boulardii) in the management and prevention of diarrhea. World J Gastroenterol 12:4557–4560
Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M, Valtonen V (2003) Safety of probiotics that contain Lactobacilli or Bifidobacteria. Clin Infect Dis 36:775–780
Bruzesse E (2006) Early administration of GOS/FOS prevents intestinal and respiratory infections in infants. J Pediatr Gastroenterol Nutr 42:E1–E110
Buts JP, De Keyser N (2006) Effects of Saccharomyces boulardii on intestinal mucosa. Dig Dis Sci 51:1485–1492
Cabana MD, Shane AL, Chao C, Oliva-Henker M (2006) Probiotics in primary care pediatrics. Clin Pediatr 45:405–410
Casburn-Jones AC, Farthing MJ (2004) Management of infectious diarrhoea. Gut 53:296–305
Cassone M, Serra P, Mondello F, Girolamo A, Scafetti S, Pistella E, Venstaditti M (2003) Outbreak of S. cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. Clin Microbiol 41:5340–5343
Castañeda C, Garcia E, Santa Cruz M, Fernandez M, Monterrey P (1995) Effects of Saccharomyces boulardii in children with chronic diarrhea, especially cases due to giardiasis. Revista Mexicana de Puericultura y Pediatria 2:12–16
Cetina-Sauri G, Sierra Basto G (1994) Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea. Ann Pediatr 41:397–400
Chouraqui JP, Van Egroo LD, Fichot MC (2004) Acidified milk formula supplemented with Bifidobacterium lactis: impact on infant diarrhea in residual care settings. J Pediatr Gatsroenterol Nutr 38:288–292
Coconnier MH, Lievin V, Bernet-Camard MF, Hudault S, Servin AL (1997) Antibacterial effect of the adhering human Lactobacillus acidophilus strain LB. Antimicrob Agents Chemother 41:1046–1052
Costa-Ribeiro H, Ribeiro TC, Mattos AP, Valois SS, Neri DA, Almeida P, Cerqueira CM, Ramos E, Young RJ, Vanderhoof JA (2003) Limitations of probiotic therapy in acute, severe dehydrating diarrhea. J Pediatr Gastroenterol Nutr 36:112–115
De Preter V, Vanhoutte T, Huys G, Swings J, Rutgeerts P, Verbeke K (2006) Effect of lactulose and Saccharomyces boulardii administration on the colonic urea-nitrogen metabolism and the bifidobacteria concentration in healthy human subjects. Aliment Pharmacol Ther 23:963–974
De Preter V, Vanhoutte T, Huys G, Swings J, De Vuyst L, Rutgeerts P, Verbeke K (2006) Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on the colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol 292:G358–G368
Duggan C, Gannon J, Waker WA (2002) Protective nutrients and functional foods for the gastrointestinal tract. Am J Clin Nutr 75:789–808
Elliott E, Teversham K (2004) An evaluation of nine probiotics available in South Africa, August 2003. SAMJ 94:121–124
Enache-Angoulvant A (2005) Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis 41:1559–1568
Fedorak RN, Madsen KI (2004) Probiotics and prebiotics in gastrointestinal disorders. Curr Opin Gastroenterol 20:146–155
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 in children with acute diarrhea: a multicenter European trial. J Pediatr Gastroenterol Nutr 30:214–216
Guarino A, Berni Canani R, Spagnuolo MI, Bisceglia M, Boccia MC, Rubino A (1997) Oral bacterial therapy reduces the duration of symptoms and viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 25:516–519
Hilton E, Kolakowski P, Singer C, Smith M (1997) Efficacy of Lactobacillus GG as a diarrheal preventive in travelers. J Travel Med 4:41–43
Höchter W, Chase D, Hagenhoff G (1990) Saccharomyces boulardii bei akuter Erwachsenendiarrhoe. Münch Med Wschr 132:188–192
Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ (2002) Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig Dis Sci 47:2625–2634
Ibnou-Zekri N, Blum S, Schiffrin EJ, von der Weid T (2003) Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro. Infect Immun 71:428–436
Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T (1991) A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics 88:90–97
Jijon H, Backer J, Diaz H, Yeung H, Thiel D, McKaigney C, De Simone C, Madsen K (2004) DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 126:1358–1373
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 8:293–296
Katelaris PH, Salam I, Farthing MJ (1995) Unspecified Lactobacillus acidophilus in prevention traveler’s diarrhea. N Eng J Med 333:1360–1361
Khanna V, Alam S, Malik A (2005) Efficacy of tyndalized Lactobacillus acidophilus in acute diarrhea. Indian J Pediatr 72:935–938
Kollaritsch H (1989) Traveller’s diarrhea among Austrian tourists to warm climate countries: II. Clinical features. Eur J Epidemiol 5:355–362
Kowalska-Duplaga K, Fyderek K, Szajewska H, Janiak R (2004) Efficacy of Trilac® in the treatment of acute diarrhoea in infants and young children - a multicentre, randomized, double-blind placebo-controlled study. Pediatria Współczesna 3:295–299
Kurugol Z, Koturoglu G (2005) Effects of Saccharomyces boulardii in children with acute diarrhoea. Acta Paediatr 94:44–47
Land MH, Rouster-Steven K, Woods Dr (2005) Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115:178–181
Lilly DM, Stillwell RH (1965) Probiotic growth promoting factors produced by microorganisms. Science 147:747–748
Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM (1999) Lactobacillus endocarditis caused by a probiotics organism. Clin Microbiol Infect 5:290–292
Mansour-Ghanaei F, Dehbashi N, Yazdanparast K, Shafaghi A (2003) Efficacy of Saccharomyces boulardii with antibiotics in acute amoebiasis. World J Gastroenterol 9:1832–1833
Marteau P, Pochart P, Bouhnik Y, Zidi S, Goderel I, Rambaud JC (1992) Survival of Lactobacillus acidophilus and Bifidobacterium sp. in the small intestine following ingestion in fermented milk. A rational basis for the use of probiotics in man. Gastroenterol Clin Biol 16:25–28
Mastretta E, Longo P, Laccisaglia A, Balbo L, Russo R, Mazzaccara A, Gianino P (2002) Effect of a Lactobacillus GG and breast-feeding in the prevention of rotavirus nosocomial infection. J Pediatr Gastroenterol Nutr 35:527–531
Michail S, Abernathy F (2002) Lactobacillus plantarum reduces the in vitro secretory response of intestinal epithelial cells in enteropathogenic Escherichia coli infection. J Pediatr Gastroenterol Nutr 35:350–355
NASPGHAN Nutrition Report Committee; Michail S, Sylvester F, Fuchs G, Issenman R (2006) Clinical efficacy of probiotics: review of the evidence with focus on children. J Pediatr Gastroenterol Nutr 43:550–557
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 22:53–56
Rautio M, Jousimies-Somer H, Kauma H, Pietarinen I, Saxelin M, Tynkkynen S, Koskela M (1999) Liver abcess due to a Lactobacillus rhamnosus strain indistinguishable from a L. rhamnosus strain GG. Clin Infect Dis 28:1159–1160
Raza S, Graham SM, Allen SJ (1995) Lactobacillus GG promotes recovery from acute nonbloody diarrhea in Pakistan. Pediatr Infect Dis J 14:107–111
Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH (1994) Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 344:1046–1049
Saint-Marc T, Rossello-Prats L, Touraine JL (1991) Efficacy of Saccharomyces boulardii in the treatment of diarrhea in AIDS. Ann Med Interne (Paris) 142:64–65
Salazar-Lindo E, Miranda-Langschwager P, Campos-Sanchez M, Chea-Woo E, Sack RB (2004) Lactobacillus casei strain GG in the treatment of infants with acute watery diarrhea: A randomized, double-blind, placebo controlled clinical trial [ISRCTN67363048]. BMC Pediatr 4:18
Saran S, Gopalan S, Krishna TP (2002) Use of fermented foods to combat stunting and failure to thrive. Nutrition 18:393–396
Sarker SA, Sultana S, Fuchs GJ, Alam NH, Azim T, Brussow H, Hammarstrom L (2005) Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh. Pediatrics 116:e221–e228
Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE (2006) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 6:374–382
Shamir R, Makhoul IR, Etzioni A, Shehadeh N (2005) Evaluation of a diet containing probiotics and zinc for the treatment of mild diarrheal illness in children younger than one year of age. J Am Coll Nutr 24:370–375
Shornikova AV, Isolauri E, Burkanova L, Lukovnikova S, Vesikari T (1997) A trial in the Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea. Acta Paediatr 86:460–465
Shornikova AV, Casas IA, Mykkanen H, Salo E, Vesikari T (1997) Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. Pediatr Infect Dis J 16:1103–1107
Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tongpradit P, Varavithya W (2000) Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 30:68–72
Sougioultzis S, Simeonidis S, Bhaskar KR, Chen X, Anton PM, Keates S, Pothoulakis C, Kelly CP (2006) Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343:69–76
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
Szajewska H, Mrukowicz JZ (2005) Use of probiotics in children with acute diarrhea. Paediatr Drugs 7:111–122
Szajewska H, Setty M, Mrukowicz J, Guandalini S (2006) Probiotics in gastrointestinal disease in children: hard and not-so-hard evidence of efficacy. J Pediatr Gastroenterol Nutr 42:454–475
Szajewska H, 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:S17–S25
Szajewska H, Skorka A, Dylag M (2007) Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment Pharmacol Ther 25;257–64
Szymanski H, Pejcz J, Jawien M, Chmielarczyk A, Strus M, Heczko PB (2006) Treatment of acute infectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosus strains-a randomized, double-blind, placebo-controlled trial. Aliment Pharmacol Ther 23:247–253
Szymanski H, Chmielarczyk A, Strus M, Pejcz J, Jawien M, Kochan P, Heczko PB (2006) Colonisation of the gastrointestinal tract by probiotic L. rhamnosus strains in acute diarrhoea in children. Dig Liver Dis 38(Suppl 2):S274–S276
Temmerman R, Pot B, Huys G, Swings J (2003) Identification and antibiotic susceptibility of bacterial isolates from probiotic products. Int J Food Microbiol 81:1–10
Thibault H, Aubert-Jacquin C, Goulet O (2004) Effects of long-term consumption of a fermented infant formula (with Bifidoacterium breve c50 and Streptococcus thermophilus 065) on acute diarrheda in healthy infants. J Pediatr Gastroenterol Nutr 39:147–152
Tissier H (1906) Traitement des infections intestinales par la méthode de la transformation de la flore bactérienne de l’intestin. C R Soc Biol 60:359–361
Van Niel CW, Feudtner C, Garrison MM, Christakis DA (2002) Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 109:678–84
Villarruel G, Rubio DM, Lopez F, Cintioni J, Gurevech R, Romero G, Vandenplas Y (2007) Saccharomyces boulardii in acute childhood diarrhea: a randomized, placebo-controlled study. Acta Paediatr (in press)
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00431-007-0585-x
Rights and permissions
About this article
Cite this article
Vandenplas, Y., Salvatore, S., Viera, M. et al. Probiotics in infectious diarrhoea in children: are they indicated?. Eur J Pediatr 166, 1211–1218 (2007). https://doi.org/10.1007/s00431-007-0497-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-007-0497-9