Probiotics for gastrointestinal disease

[Dr.]

Почитаем про дисбактериоз. Как всегда, "Enthusiasm for probiotics has outpaced the scientific evidence. Large, well-designed multicenter controlled clinical trials are needed to clarify the role of specific probiotics in different patient populations" (энтузиазм по поводу пробиотиков на данный момент не соответствует их научной доказанности. Требуются большие мультицентровые контролируемые исследования с хорошим дизайном для уточнения роли специфических пробиотиков в различных популяциях пациентов - перевод мой)

R Balfour Sartor, MD

UpToDate performs a continuous review of over 375 journals and other resources. Updates are added as important new information is published. The literature review for version 15.3 is current through August 2007; this topic was last changed on September*20,*2007. The next version of UpToDate (16.1) will be released in March 2008. [/size]
INTRODUCTION*—*The intestinal tract is host to a vast ecology of microbes, which are necessary for health but also have the potential to contribute to the development of diseases by a variety of mechanisms. Perturbations in the intestinal epithelium, for example, can lead to an inflammatory response resulting directly from microbial products that alter the underlying epithelium or allow bacterial and food antigens to stimulate the mucosal immune system. (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease").

Interactions between intestinal microbes and the host are the subject of intensive ongoing research since they may influence a variety of diseases. Part of this research involves the deliberate manipulation of the intestinal microflora with a therapeutic intention. The greatest experience has been in the inflammatory bowel diseases, ulcerative colitis, Crohn's disease and pouchitis, although clinical trials are emerging in several other conditions.

There are three general methods by which the intestinal microflora can be altered: administration of antibiotics, prebiotics (ie, dietary components that promote the growth and metabolic activity of beneficial bacteria), or probiotics (ie, beneficial bacteria). Combination of these methods is also possible (synbiotics). Interest in these approaches has extended well beyond the clinical sciences since a role for intestinal microbes in health and disease has been recognized in alternative and complementary forms of medicine for many years [1]. In comparison, systematic evaluation of efficacy is relatively recent. This topic review focuses on clinical trials of probiotics in gastrointestinal disease.

DEFINITION*—*Probiotics are microorganisms that have beneficial properties for the host. Most have been derived from food sources, especially cultured milk products. The list of such microorganisms continues to grow and includes strains of lactic acid bacilli (eg, Lactobacillus and Bifidobacterium), a nonpathogenic strain of E. coli (eg, E. coli Nissle 1917), Clostridium butyricum, Streptococcus salivarius, and Saccharmomyces boulardii (a nonpathogenic strain of yeast). Also under development are strains of bacteria that have been genetically engineered to secrete immunomodulators (such as interleukin-10 or trefoil factors), which have the potential to favorably influence the immune system [2,3].

Initial studies of selected probiotic species (given alone or in combination) have suggested potential efficacy in several gastrointestinal illnesses, the best studied of which are the inflammatory bowel diseases (particularly pouchitis) [4-10]. Therapeutic benefit has also been suggested in several other disorders including antibiotic-related diarrhea, Clostridium difficile toxin-induced colitis, infectious diarrhea, hepatic encephalopathy, irritable bowel syndrome, and allergy.

MECHANISMS OF BENEFIT*—*Mechanisms for the benefits of probiotics are incompletely understood. However, three general benefits have been described [10]: Suppression of growth or epithelial binding/invasion by pathogenic bacteria Improvement of intestinal barrier function Modulation of the immune system. Several probiotic preparations induce protective cytokines, including IL-10 and TGF-beta, and suppress proinflammatory cytokines, such as TNF, in the mucosa of patients with pouchitis and Crohn's disease, in IL-10-/- mice, and in isolated splenocytes [11-14]. Saccharomyces boulardii limited the migration of T-helper 1 cells in inflamed colon tissue in a mouse model of inflammatory bowel disease [15]. Modulation of pain perception. Some Lactobacillus strains appear to induce expression of micro-opioid and cannabinoid receptors in intestinal epithelial cells and mediate analgesic functions in the gut in a manner similar to the effects of morphine [16].

Probiotics differ in their ability to resist gastric acid and bile acids, colonize the intestinal tract, and influence cytokines secreted by intestinal epithelial cells [11,12,17-22]. Thus, not all probiotics are alike; as a result, benefits observed clinically with one species or combination of species are not necessarily generalizable to another.

Although yogurt is commonly recommended as a source of probiotics, not all of the live cultures contained in yogurt survive well in an acidic environment nor do they colonize the microflora efficiently [23,24]. Furthermore, the residual lactose contained in yogurt can increase symptoms in patients with lactose intolerance including those who develop secondary lactose intolerance due to an antecedent gastroenteritis (a setting in which probiotics have been recommended). Fermented dairy beverages containing much higher concentrations of live cultures than yogurt or cultures that are relatively resistant to gastric acid are also available.

An interesting observation has been that it may not be necessary to administer living organisms to achieve a benefit. Secreted proteins and DNA of one probiotic preparation (VSL#3, Nature's Pharmaceuticals, Inc.) blocked cytokine activation and prevented apoptosis of epithelial cells [25,26]. The effects depended upon the specific DNA from the different bacterial species that were components of the preparation [25]. Non-methylated DNA from VSL#3 as well as other randomly selected E. coli strains suppressed experimental colitis in several animal models [27]. These therapeutic effects are mediated through toll-like receptor 9 and with induction of type 1 interferons alpha/beta [28].

POUCHITIS*—*For the surgical treatment of ulcerative colitis (UC) and familial adenomatous polyposis, proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the favored alternative to proctocolectomy with permanent ileostomy since it preserves intestinal continuity and sphincter function and removes the entire colorectal mucosa. This procedure consists of total abdominal colectomy, stripping of the rectal mucosa with preservation of the anal sphincter, and the construction of an ileal pouch that is anastomosed to the anus. As an alternative, the pouch can be stapled to a short segment of retained rectum.

The most frequently observed long-term complication of IPAA is acute and/or chronic inflammation of the ileal reservoir, called pouchitis. Symptoms of pouchitis include increased stool frequency, urgency, hematochezia, abdominal pain, fever, and extraintestinal manifestations of inflammatory bowel diseases. (See "Pouchitis"). Pouchitis complicates approximately 20 percent of ulcerative colitis patients in the first year after creation of the IPAA, but less than 1 percent of patients with familial polyposis.

Detailed studies of the microflora in patients with pouchitis have demonstrated unique patterns including the persistence of Fusobacter and enteric species and the absence of Streptococcus species in the inflamed pouch [29]. The observations support a role for bacteria in the pathogenesis of pouchitis and provide a rationale for clinical trials aimed at altering the microflora.

Small controlled trials have suggested that at least one probiotic preparation (VSL#3) containing 5 X 10 (11) per gram of four strains of lactobacilli, three strains of bifidobacteria, and one strain of Streptococcus salivarius subspecies thermophilus may be effective in prevention of pouchitis. A randomized placebo controlled trial included 40 patients with a history of chronic, relapsing pouchitis who were placed into clinical and endoscopic remission with broad spectrum antibiotics [30]. Patients were randomly assigned to VSL#3 6 g/day or placebo. After nine months of daily treatment, significantly fewer patients in the probiotic group had experienced a relapse (15 versus 100 percent).

[Dr.]

Within three months of stopping treatment, all patients in the VSL#3 group had relapsed. Likewise, fecal lactobacillus and bifidobacterial concentrations returned to pretreatment levels within one month after therapy was discontinued, indicating that permanent colonization with the probiotic species did not occur. A second study from the same group included 36 patients with recurrent or refractory pouchitis who had required antibiotics at least twice in the previous year [31]. After achieving remission, patients were randomly assigned to VSL#3 or placebo once daily for one year. Significantly more patients in the probiotic group remained in remission (85 versus 6 percent). Patients randomized to VSL#3 also had significantly better quality of life. A third study from the same group included 40 consecutive patients who underwent IPAA for ulcerative colitis [32]. Patients were randomly assigned to receive VSL#3 3 g/day or placebo immediately after ileostomy closure for one year. Patients receiving the probiotic had significantly fewer episodes of pouchitis (10 versus 40 percent). Probiotic treatment was also associated with significant improvement in quality of life compared with placebo. Somewhat different conclusions were reached in an observational study involving 31 patients with antibiotic-dependent pouchitis who were treated with VSL#3 after achieving remission with ciprofloxacin [33]. After eight months, only a minority of patients remained on priobiotic therapy and in symptomatic remission (most having stopped it due to recurrence of symptoms or adverse effects).

No benefit from another probiotic (Lactobacillus rhamnosus GG) was found in another, albeit small, controlled trial [34]. Furthermore, only 40 percent of patients who received the probiotic became colonized.

ULCERATIVE COLITIS — Various probiotic species have shown promise in the treatment of ulcerative colitis in small studies, although a clear clinical benefit remains to be established [35-45]. Prevention of relapse is more thoroughly documented than treatment of active disease. The following are illustrative controlled trials. E. coli 1917 Nissle was as effective as low dose 5-ASA in preventing relapse of ulcerative colitis in at least two controlled trials [35,36]. The combination of VSL#3 plus balsalazide was slightly more effective than balsalazide or mesalazine alone in a controlled trial of patients with acute mild-to-moderate ulcerative colitis [38]. The combination of a prebiotic and a probiotic (Bifidobacterium longum) was associated with improvement in histologic scores and measures of immune activation in a one-month randomized controlled trial [41]. Lactobacillus GG appeared to be more effective than standard treatment involving mesalazine in prolonging relapse-free time but did not influence relapse rates in patients with quiescent ulcerative colitis [46].

CROHN'S DISEASE — Clinical trials of probiotics in Crohn's disease have shown mixed results [47]. The reasons for the heterogeneity are unclear but could be due to several factors such as the specific probiotics (and doses) used, differences in study duration, characteristics of the included patients (eg, location of disease), and endpoints that were measured. In aggregate, the available data do not clearly demonstrate clinical effectiveness. Whether certain subgroups might benefit remains to be determined. E. coli Nissle was more effective than placebo in preventing relapse of Crohn's disease in remission [48]. Three of four children were successfully tapered off steroids following administration of Lactobacillus GG [49]. Studies evaluating probiotics for prevention of postoperative relapse have produced mixed results with most studies being negative [50]. (See "Medical prophylaxis of postoperative Crohn's disease").

ANTIBIOTIC-ASSOCIATED DIARRHEA — Multiple studies have evaluated a variety of probiotics in the treatment and prevention of antibiotic-associated diarrhea [51,52]. Many were small, used different endpoints, and had serious methodological problems that limited comparisons among them. Nevertheless, several systematic reviews have been conducted [53-63], most of which (although using different sets of primary studies) reached similar conclusions.

One of the largest and most recent meta-analyses (34 placebo-controlled trials) concluded that probiotics were [60]: Associated with a 52 percent reduction in antibiotic-associated diarrhea (95% CI 35-65%) An 8 percent reduction in traveler's diarrhea (95% CI -6 to 21%) A 57 percent reduction in risk of acute diarrhea of various causes in children (95% CI 37-51%) and a 26% reduction in adults (95% CI 7-49%) The protective effects did not vary significantly among the probiotics strains Saccharomyces boulardii, Lactobacillus rhamnosus, GG, Lactobacillus acidophilus, Lactobacillus bulgaricus and other strains used alone or in combination of two or more strains.

A later meta-analysis that focused on studies of children found a protective effect of probiotics on antibiotic associated diarrhea on per-protocol analysis but results were not significant on intention-to-treat analysis [63].

Notably, not all of the included studies used similar definitions of antibiotic-associated diarrhea. In particular, the pooled analysis combined all cases of diarrhea whether or not they were due to the presence of Clostridium difficile (C. difficile) toxin. The degree of overall benefit for primary prevention of C. difficile infection (or prevention of recurrence) was not reported. Similarly, there were insufficient data to describe potential associations with the type of antibiotics used, duration of therapy, or the dose and duration of the probiotic preparation.

Another systematic review that focused on studies in which C. difficile was specifically sought concluded that there was insufficient evidence for routine clinical use of probiotics to prevent or treat C. difficile diarrhea [64].

In summary, the available data are limited with respect to the size and quality of studies from which to draw conclusions. Systematic reviews suggest that probiotics (including various bacterial species and the yeast S. boulardii) are effective in reducing the incidence of diarrhea in patients who are taking antibiotics. However, discordant data have been published and there is little detailed information regarding the optimal dose or timing of supplementation or the effects on subgroups of patients. Whether probiotics can shorten the period of diarrhea in patients who have already developed it is unclear.

Studies focusing specifically on C. difficile diarrhea are inconclusive regarding a benefit on treatment or prevention. While probiotics used in such studies are generally safe, case reports have described Saccharomyces cervisiae fungemia and deaths particularly in immunosuppressed and critically ill patients who received a commercial preparation of S. boulardi (genomically identical to S. cervisiae) for either treatment or prevention of C. difficile diarrhea [65]. Thus, routine use cannot be recommended.

INFECTIOUS DIARRHEA — Several studies have evaluated a variety of probiotics in the treatment of infectious diarrhea. Results have been summarized in at least five systematic reviews all of which found an overall reduction in the duration of diarrhea (by about 17 to 30 hours), although there was heterogeneity among studies [55,66-69]. Probiotics were generally safe, with no serious adverse effects reported. The following illustrate the range of findings. One focused on randomized, placebo-controlled studies in infants and children with acute diarrhea [67]. Probiotics were associated with a significant reduction in the risk of diarrhea lasting for more than three days (RR 0.40, 95% CI 0.28 to 0.57). Only Lactobacillus GG showed a consistent beneficial effect. Probiotics significantly reduced the duration of diarrhea (by about 20 hours) compared with placebo, particularly in gastroenteritis caused by rotavirus. A second meta-analysis included a total of nine studies evaluating several strains of lactobacilli in children [55]. Those who received recent antibiotics were excluded. Probiotics reduced the duration of diarrhea by 0.7 days (95% CI 0.3 to 1.2) and diarrhea frequency on day two by 1.6 stools per day. The authors were able to detect a linear dose-response relationship across studies; a minimum of 10 billion colony-forming units during the first 48 hours was needed to reduce the duration of diarrhea by more than one-half a day. A third meta-analysis that included 23 studies (using several different probiotic preparations) in adults and children found that probiotics reduced the overall risk of having diarrhea at three days by about 35 percent (relative risk 0.66, 95 percent CI 0.55-0.77), and the mean duration of diarrhea by about 30 hours (95 percent CI 19 to 43 hours) [66]. The authors concluded that probiotics were a useful adjunct to rehydration therapy in treating acute, infectious diarrhea in adults and children. A meta analysis of 12 studies examining probiotics for the prevention of traveler's diarrhea concluded that several products, including Saccharomyces boulardii and a combination of Lactobacillus acidophilus and Bifidobacterium bifidum, reduced the risk of travelers diarrhea (RR 0.85, 95% CI 0.79-0.91) with no serious adverse effects [68].

[Dr.]

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].

[Dr.]

SUMMARY AND RECOMMENDATIONS — Several probiotic preparations have promise in prevention or treatment of various conditions. However, most studies have been small and many have important methodologic limitations, making it difficult to make unequivocal conclusions regarding efficacy, especially when compared with proven therapies. Furthermore, considerable differences exist in composition, doses, and biologic activity between various commercial preparations, so that results with one preparation cannot be applied to all probiotic preparations. Finally, costs to the patient may be considerable, since no preparation is FDA approved and hence are not reimbursed by insurers. Enthusiasm for probiotics has outpaced the scientific evidence. Large, well-designed multicenter controlled clinical trials are needed to clarify the role of specific probiotics in different patient populations.

Because they are generally safe, the decision to use a probiotic rests mostly upon the degree of anticipated benefit, available alternatives, the clarity of the available data in showing a benefit, costs, and patient preferences. No probiotic strategy is currently considered to represent the standard of care for any of the conditions described above. The following recommendations are based upon the author's overall appraisal of the quality and consistency of the available evidence.

Pouchitis — Limited data from small controlled trials suggests a benefit from VSL#3 in the primary and secondary prevention of pouchitis. Thus, it is a reasonable option in addition to standard medical therapy, although long-term efficacy is uncertain. (See "Pouchitis").

Ulcerative colitis — A benefit of probiotics in ulcerative colitis remains unproven, but E. coli Nissle 1917 shows promise in maintaining remission and could be considered as an alternative in patients intolerant or resistant to 5-ASA preparations. Unfortunately, this preparation is not available in the United States. No other probiotic preparation has been validated for this indication.

Crohn's disease — A benefit of probiotics in Crohn's disease remains unproven.

Antibiotic associated diarrhea — Large, well-conducted studies are needed before probiotics can be recommended routinely for antibiotic associated diarrhea.

Infectious diarrhea — It is reasonable to recommend probiotics to adults and children with presumed infectious diarrheal illness with the hope of reducing the duration of symptoms by 17 to 30 hours. Probiotics that were effective in at least one controlled trial included Lactobacillus strain GG, Lactobacillus reuteri, combination Lactobacillus rhamnosus and Lactobacillus reuteri, and combination Lactobacillus acidophilus and Lactobacillus bifidus. The minimal effective dose appears to be 10 billion colony-forming units given within the first 48 hours.

Irritable bowel syndrome — A benefit of probiotics for IBS remains unproven.

Lactose intolerance — A benefit of probiotics for lactose intolerance remains unproven.

Hepatic encephalopathy — Initial studies in mild hepatic encephalopathy are encouraging. However, the role of probiotics remains unproven.

Allergy — A definitive role of probiotics for allergic conditions remains unproven, although initial results in studies of children with a variety of preparations are promising

[easl]

Уважаемые коллеги!
Не касаясь святого - нашего отношения к термину "дизбактериоз", тем не менее меня все-таки смущает несколько однобокий подход в рекомендациях по применению пробиотиков. Я в своих консультациях стараюсь обходить этот вопрос, как Вы заметили.
Вчера прочитал статью, которую хочу предложить Вашему вниманию без перевода (он не сложен). Хотя, если есть необходимость, то и перевод сделаю.
Прошу высказать отношение к предмету обсуждения. Конечная цель обсуждения - выработать единый подход к рекомендациям по назначению пробиотиков в различных ситуациях.
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[Ссылки доступны только зарегистрированным пользователям ]
Benefits of Probiotics Reviewed CME/CE
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Authors and Disclosures
Laurie Barclay, MD
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.Laurie Scudder, MS, NP-C
Disclosure: Laurie Scudder, MS, NP-C, has disclosed no relevant financial information. Brande Nicole Martin
Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

November 6, 2008 — Probiotics are microorganisms that may be helpful for conditions such as antibiotic-associated diarrhea, infectious diarrhea, irritable bowel syndrome, and atopic dermatitis in at-risk infants, according to a review published in the November 1 issue of American Family Physician.
"Probiotics are live microorganisms that benefit the health of the host when administered in adequate amounts," write Benjamin Kligler, MD, MPH, from Albert Einstein College of Medicine of Yeshiva University, and Andreas Cohrssen, MD, from the Beth Israel Residency Program in Urban Family Practice, both in New York, New York. "Several mechanisms have been proposed to explain the actions of probiotics. In most cases, it is likely that more than one mechanism is at work simultaneously."
Because of these multiple mechanisms of action, many different probiotics have potential applications to various diseases. Those in most widespread use, which have undergone the most clinical testing, include Lactobacillus species (such as L acidophilus, L rhamnosus, L bulgaricus, L reuteri, and L casei); Bifidobacterium species; and Saccharomyces boulardii, which is a nonpathogenic yeast.
Efficacy of a probiotic species taken orally requires that it be resistant to acid and bile so that it can pass through the upper gastrointestinal tract without loss of biological potency. However, even the hardiest microorganisms must be administered regularly to maintain colonization and typically can no longer be cultured from stool samples more than 1 to 2 weeks after ingestion of the probiotic.
Probiotics are considered to be both safe and effective for preventing and treating antibiotic-associated diarrhea and infectious diarrhea. The probable mechanism of action may be a combination of direct competition between pathogenic bacteria in the gut and immune modulation and enhancement.
Other specific applications supported to some degree by available studies include relief of gastrointestinal tract symptoms in irritable bowel syndrome and therapy for pediatric atopic dermatitis.
Although probiotics are sometimes used for other conditions, evidence is lacking to support these indications, and they were therefore not discussed in this review. These conditions include vaginal candidiasis, stomach infection with Helicobacter pylori, inflammatory bowel disease, and upper respiratory tract infections.
On the basis of dosages used in clinical studies documenting efficacy, frequently used dosages range from 5 to 10 billion colony-forming units per day for children and from 10 to 20 billion colony-forming units per day for adults, although these vary based on the specific microorganism or combination used. In most studies, the dosages of S boulardii range from 250 to 500 mg/day.
Probiotics have no reported drug interactions. Common adverse effects are mild and self-limited, including flatulence and mild abdominal discomfort. Septicemia and other severe adverse effects may rarely occur, and these have only been reported in severely ill or immunocompromised hosts or in children with short-gut syndrome. Therefore, probiotics should be used only with caution in patients with short-gut syndrome, and they are contraindicated in patients with conditions that severely compromise the immune system.
Available formulations of probiotics include capsules, powder, tablets, liquid, or incorporated into food.
The cost of probiotic therapy ranges from $8 to $22 for a 1-month supply. For information regarding the quality of different products, clinicians should consult the Consumer Lab Web site or other objective sources. Other useful Web sites are usprobiotics.org and the National Center for Complementary and Alternative Medicine's Web site.
Specific clinical recommendations, and their accompanying level of evidence rating, are as follows:
• Probiotics may help prevent antibiotic-related diarrhea (level of evidence, A). For this indication, use of S boulardii and L rhamnosus GG are best supported by the available evidence.
• In a recent meta-analysis, probiotics reduced the risk for the development of antibiotic-associated diarrhea by 52%, and the benefit was greatest when probiotic therapy was initiated within 72 hours of starting antibiotic treatment.
• In all-cause infectious diarrhea, probiotic therapy may decrease both the duration of illness and the severity of symptoms, based on a large Cochrane review and meta-analysis including studies of viral diarrhea and traveler's diarrhea (level of evidence, A).
• In that review, probiotics were associated with a significant (34%) reduction in the risk for diarrhea at 3 days, and the mean duration of diarrhea was reduced by approximately 30 hours, leading the authors to conclude that probiotics may be a useful adjunct to rehydration therapy in treating acute infectious diarrhea in adults and children.
• In patients with irritable bowel syndrome, probiotic therapy may decrease the severity of pain and abdominal bloating, based on small studies performed thus far (level of evidence, B).
• For at-risk infants, probiotics may help prevent atopic dermatitis (level of evidence, B), and some preliminary evidence suggests that symptoms of atopic dermatitis may also respond to probiotic therapy.
"Because some labels are unreliable, physicians should recommend specific brands known to be of reasonable quality or encourage patients to research brands before purchasing a specific product," the review authors conclude. "For patients who dislike taking pills or powder, therapeutic yogurt preparations may be preferred option....More studies are warranted on many food sources of probiotics to provide confidence in effectiveness and dose recommendations."

The review authors have disclosed no relevant financial relationships.Am Fam Physician. 2008;78:1073-1078.

[riltsov]

Сообщение от easl

Уважаемые коллеги!
Не касаясь святого - нашего отношения к термину "дизбактериоз",

Для меня очевидно, что отрицание дисбактериоза, как самостоятельного диагноза, не может быть основанием для отрицания эффективности пробиотиков при ряде заболеваний.

Дисбактериоз – действительно псевдодиагноз и нет оснований для выделения такой нозологической единицы. Однако, в основе ряда случаев антибиотик- ассоциированной диареи лежит нарушение микробного баланса кишечника. И меня несколько обескураживает позиция некоторых уважаемых консультантов безапелляционно утверждающих, что понос от антибиотиков не связан с микробным дисбалансом.

Не надо с водой выплескивать ребенка. Нет диагноза дисбактериоз. Но нарушения микробного баланса есть. И пробитики есть с вменяемой доказательной базой.

В статье приведены приемлемые и обоснованные показания для назначения пробиотиков.

[Darina38]

Вот что нашла про интересующей Вас теме.
[Ссылки доступны только зарегистрированным пользователям ]
Summary
Probiotics for the prevention of pediatric antibiotic-associated diarrhea (AAD)
Antibiotic-associated diarrhea (AAD) occurs when antibiotics disturb the natural balance of "good" and "bad" bacteria in the intestinal tract causing harmful bacteria to sometimes multiply beyond their normal numbers. The symptoms of AAD may include frequent watery bowel movements and crampy abdominal pain. Probiotics are dietary supplements containing potentially beneficial bacteria or yeast. Probiotics are thought to restore the natural balance of bacteria in the intestinal tract. Ten studies were reviewed and provide the best evidence we have. Study quality was mostly good overall. The studies tested 1986 children (aged 0 to 18 years) who were receiving probiotics co-administered with antibiotics to prevent AAD. The subjects received probiotics (Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination), placebo (fake pills), other treatments thought to prevent AAD (i.e. diosmectite or infant formula) or no treatment. The studies were short term and ranged in length from 15 days to 3 months. An analysis that included only patients who completed the studies showed that probiotics may be effective for preventing AAD. However, a more conservative analysis that counted study drop-outs as treatment failures did not show any differences between probiotic and comparison groups. Probiotics were generally well tolerated and side effects occurred infrequently. Although current data are promising, there is insufficient evidence to routinely recommend the use of probiotics for the prevention of pediatric AAD.

А вообще исследований по эффективности пробиотиков в разных сферах достаточно много.
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[Dr.]

Тема боян! Предлагаю объединить с : http://forums.rusmedserv.com/showthread.php?t=50513

Ничего ж секретного в ней нет

[easl]

Давайте объединим, согласен. Но не ради самого объединения, а чтобы сделать конкретные рекомендации для всех нас по этому вопросу уже в русском варианте, на которые могли бы ссылаться при консультациях. И хорошо бы краткую информацию для пациентов приколоть. А то у нас часто получается так: диагноз "дизбактериоз" не существует и выкиньте все бактерины и т.п.

[Hannah]

Я все время спорю со своим зав.кафедрой, который пытается меня научить про дисбактериоз, виноватый во всех бедах наших детей. Консультируя родителей на рмс, мы очень легко говорим о том, что такого диагноза нет и вообще надо забыть про биоценоз кишечника и его исследование. Но все же микрофлора в кишечнике есть, и изменение ее состава несомненно является одним из звеньев патогенеза ряда заболеваний.

Тут есть еще другая проблема - в сознании наших врачей "пробиотики" - это все что угодно, содержащее какую угодно флору. Все исследования же касаются конкретных микроорганизмов в конкретных количествах и конкретных ситуациях. Такое примение этой группы препаратов сильно отличается от принятого у нас, когда назначаются по какой-то причине милые сердцу конкретного врача пробиотики всем подряд для "поддержания организма", "подкрепления иммунитета" или "лечения дисбактериоза".

[denis_doc]

Есть микрофлора! Только зачем назначать пробиотики, если микрофлору восстанавливает Актимель, а иммунитет поднимает Иммунель? Об этом и в телевизоре говорят!

For at-risk infants, probiotics may help prevent atopic dermatitis (level of evidence, B), and some preliminary evidence suggests that symptoms of atopic dermatitis may also respond to probiotic therapy.

статей на эту тему, действительно, много. И что интересно, статей о том, что пробиотики противопоказаны при атопиях у детей нет. Как вы думаете, с чем это связано?

[dr.Ira]

Хотелось бы обратить внимание коллег на эту фразу:The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.

[Ссылки доступны только зарегистрированным пользователям ]

[dr.Agapov]

В последние 6 месяцев с момента появления в России препарата,содержащего Lactobacillus rhamnosus GR-1 и Lactobacillus reuteri RC-14,назначаю его перорально в терапии бактериального вагиноза.
Эвиденса много:у меня в блоге [Ссылки доступны только зарегистрированным пользователям ]
Практические результаты пока неощутимы - т.е. разницы между стандартным курсом и стандартным курсом + пробиотик особенной нет.Failure бывает там и там.

[Dr.Anisimova]

Дело в том, что пробиотики почему-то принято назначать местно после лечения любого ИППП антибиотиком для "восстановления" флоры. Вообще любое назначение антибиотика сопровождается "восстановлением" пробиотиками
По антибиотикассоциированную диарею на форуме уже давно обсуждали, что это является показанием. Но таких пациентов на форуме немного.
http://forums.rusmedserv.com/showthr...EE%F2%E8%EA%E8
http://forums.rusmedserv.com/showthr...EE%F2%E8%EA%E8
При экземе доказанна их неэффективность:
http://forums.rusmedserv.com/showpos...25&postcount=1
Про диарею-уже такие данные давно есть на форуме. По бак. вагинозу спасибо, важно.

[Hard]

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no conclusive evidence of probiotics providing health benefits