Whether these modest benefits would justify the routine use of probiotics in acute diarrheal illnesses is unclear since most acute diarrheal illnesses are self-limited. The potential benefit may be greatest in settings in which patients are at risk for complications such as malnourished children in developing nations. However, most studies focused on healthy individuals living in industrialized countries. There is very little information regarding whether probiotics reduce important complications of diarrheal illness such as dehydration, a benefit that would have particular importance in developing nations. Furthermore, the data do not provide a clear understanding of the type, dose, or duration of probiotic treatment that is required to achieve a clinical benefit, or the relationship between various probiotics and protection from specific etiologic agents.
Until further data are available, it is reasonable to recommend probiotics to adults and children with presumed infectious diarrheal illness acknowledging the limitations of the data and the modest expected benefit. Probiotics that were effective in at least one controlled trial included Lactobacillus rhamnosus strain GG, Lactobacillus reuteri, combination Lactobacillus rhamnosus and Lactobacillus reuteri, and combination Lactobacillus acidophilus and Lactobacillus bifidus. Limited data suggest that the minimal effective dose in children is 10 billion colony forming units given within the first 48 hours.
IRRITABLE BOWEL SYNDROME*—*Several controlled trials of probiotics in irritable bowel syndrome (IBS) have been published, many of which can be criticized for methodologic limitations [70-76]. All were short-term studies and none has provided clear evidence as to the potential role of probiotic treatment. Furthermore, the magnitude of benefit in studies with positive results was modest, suggesting that probiotics are unlikely to have a major impact on the management of IBS.
However, it is possible that a clinically important benefit might be achieved in certain subgroups of patients, particularly those with diarrhea-predominant symptoms. The following summarizes results from some of the largest controlled trials. The probiotic Bifidobacterium infantis was significantly more effective than placebo at four weeks in a controlled trial of 362 patients with IBS [76]. However, the benefit was confined to only one of three doses tested and there was no clear dose-response relationship. 77 patients with IBS were randomly assigned to a malted milk drink containing Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624 or to a malted milk drink alone [77]. Symptoms were significantly improved at most time points in the group receiving B. infantis. There was a corresponding normalization in the ratio of serum IL-10/IL-12 suggesting that the probiotic may help reduce a proinflammatory state associated with IBS. 60 patients with IBS were randomly assigned to Lactobacillus plantarum (DSM 9843) or placebo for four weeks [75]. Flatulence was significantly reduced in the probiotic group compared with placebo while abdominal pain was reduced to a similar extent in both groups. Better overall gastrointestinal function was maintained at 12 months in the probiotic group compared with placebo, although there was no difference in bloating. 50 patients with IBS, according to Rome II criteria, were randomly assigned to a probiotic preparation containing the combination of Lactobacillus plantarum LPO 1 and Bifidocterium breve BRo or placebo for four weeks [70]. Pain and severity scores decreased significantly in the probiotic group after 14 days of treatment. 25 patients with diarrhea-predominant IBS were randomly assigned to VSL#3 or placebo twice daily for eight weeks [71]. At the end of the study, there was no significant difference in colonic transit compared with baseline. However, abdominal bloating was significantly reduced in the probiotic group compared with placebo. No changes in other abdominal symptoms such as pain, gas, or urgency were observed. Improvement in abdominal pain and a trend towards normalization of stool frequency in constipated patients was found in the probiotic treated group in a placebo-controlled trial of 40 patients randomly assigned to Lactobacillus plantarum 299V or placebo [73]. In contrast, no benefit was observed in a second placebo-controlled trial [72]. 25 patients with IBS were randomly assigned to Lactobacillus GG or placebo in a double-blind crossover trial [74]. No significant differences were observed in symptoms scores for pain, urgency or bloating. A trend toward reduction in the number of unformed stools was observed in a subgroup with diarrhea predominant symptoms.
LACTOSE INTOLERANCE*—*Ingestion of lactase-containing probiotics has the potential to aid lactose digestion in patients with lactose intolerance. Several studies have evaluated the benefit of various probiotics in patients with lactose intolerance [78]. A systematic review of 10 controlled trials found inconsistent results and suggested further studies on specific strains in which a benefit was suggested [78].
COLLAGENOUS COLITIS*—*Collagenous colitis, a type of microscopic colitis, is a diarrheal illness characterized by the presence of a thickened subepithelial collagenous plate and lymphocytic infiltrate in the colonic mucosa. (See "Lymphocytic and collagenous colitis (microscopic colitis)").
A possible benefit of E. coli strain Nissle 1917 was suggested in an open-label study of 14 patients [79]. The authors hypothesized that the benefit may have been due to an antagonistic effect of the probiotic against strains of Yersinia species. In a second placebo-controlled trial a combination of Lactobacillus acidophilus and Bifidobacterium animalis strains had no significant effect on primary end points but were associated with some improvement in symptoms [80].
DIVERTICULAR COLITIS*—*Infrequently, patients with diverticular disease develop a segmental colitis most commonly in the sigmoid colon, which can occasionally be symptomatic. Combination therapy with VSL#3 and an oral beclomethasone dipropionate (not available in the United States) was beneficial in a case series. (See "Diverticular colitis").
HEPATIC ENCEPHALOPATHY*—*Alteration of gut flora (either with probiotics or with prebiotics such as fermentable fiber) has been associated with improvement in hepatic encephalopathy in pilot studies [81-84]. Such therapy appears to lower blood ammonia concentrations, possibly by favoring colonization with acid-resistant, non-urease producing bacteria [81]. The role for this therapeutic approach is still being elucidated.
ALLERGY*—*Probiotics have the potential to reduce intestinal permeability and the generation of proinflammatory cytokines that are elevated in patients with a variety of allergic disorders. Thus, a growing number of studies have evaluated probiotics in allergic conditions including rhinitis, atopic dermatitis, and food allergy [85]. A definitive role for any of these indications remains unproven, although initial results in studies of children are promising. The following studies illustrate the range of findings: One study included 80 children and adolescents who were randomly assigned to fermented milk with or without the addition of Lactobacillus paracasei-33 for 30 days [86]. Overall scores on a pediatric rhinoconjunctivitis quality of life questionnaire improved significantly relative to placebo. No adverse effects were reported. Lactobacillus GG or placebo was given prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis or asthma, and postnatally for six months to their infants [87]. The frequency of atopic eczema in the probiotic group was significantly reduced in the children at two years of age (relative risk 0.51, 95% CI 0.32-0.84). A follow-up report suggested that the benefit persisted for at least four years [88]. A combination of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460 administered for six weeks to children with atopic dermatitis was significantly more effective than placebo in improving dermatologic symptoms [89]. The response was most pronounced in children with at least one positive skin prick test response and elevated IgE levels. No benefit from Lactobacillus rhamnosus supplementation was observed in a placebo-controlled trial in children with birch pollen allergy [90]. A hydrolyzed whey formula plus Lactobacillus GG was more effective than a hydrolyzed whey formula alone in a controlled trial of infants with atopic eczema and cow's milk allergy [91].
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