Probiotics in the management of children with allergy and other disorders of intestinal inflammation.

Soon after birth, the human gastrointestinal tract quickly becomes colonised by a variety of bacterial species. Throughout life the gastrointestinal tract continues to serve as host to a complex society of nonpathological bacteria. Microorganisms, such as probiotics, have the potential to modulate mucosal immune response and reduce gastrointestinal inflammation caused by a variety of infectious and allergic events. The most widely studied genera of probiotics are lactobacilli and bifidobacteria. Lactobacillus rhamnosis strain ATC53103 (LGG) can replenish gut flora during infectious diarrhoeal episodes. This beneficial effect is carried over to traveller's diarrhoea and children experiencing antibiotic-associated diarrhoea. Furthermore, LGG can reduce the risk of respiratory tract infections in children attending daycares and hospitals. With allergic disease on the rise, probiotics have the potential to positively impact atopic dermatitis, asthma, and allergic rhinitis. LGG has been shown to decrease the severity and delay the onset of atopic dermatitis. Additionally, LGG is beneficial in the treatment of allergic colitis and necrotising entercolitis. Some strains of probiotics appear to be useful in the treatment and/or prevention of allergic disease, however, caution must be used when generalising the effectiveness of a specific strain of organism to other organisms and other disease states.

Functional liver recovery parallels autologous gut salvage in short bowel syndrome.

BACKGROUND/PURPOSE: Parenteral nutrition (PN) is life saving in short bowel syndrome. However, long-term parenteral nutrition is frequently complicated by a syndrome of progressive cholestatic liver disease that is considered to be irreversible beyond the early stages of cholestasis, particularly in the presence of any degree of fibrosis in the liver. The purpose of this study was to examine apparent improvement in PN-associated liver dysfunction in a cohort of children with short bowel syndrome. METHODS: A retrospective case-record review of all patients managed within a dedicated Intestinal Rehabilitation Program (IRP) identified 13 patients with short bowel who had PN-associated liver dysfunction, defined for this purpose as hyperbilirubinemia or an abnormal liver biopsy. RESULTS: At referral, 12 of the 13 patients were exclusively on PN, and one was on 50% PN. At current follow-up, 3 patients have achieved complete enteral autonomy from PN, and 7 patients have had smaller decrements in PN requirements. Specific operative procedures to improve intestinal function were undertaken in 11 patients; 4 patients also underwent cholecystectomies with biliary irrigation at the time of intestinal reconstruction. The median highest bilirubin level in these 13 patients was 10.7 mg% (range, 3.2 to 24.5 mg%). Liver biopsy results indicated that 5 patients were cirrhotic, 3 had bridging fibrosis, and 4 had severe cholestasis or lesser degrees of fibrosis. Of 10 survivors in this series, 9 patients currently have a serum bilirubin less than 1 mg% with a median bilirubin in the group of 0.6 mg% (range, 0.3 to 6.4 mg%). Twelve of the 13 patients in this series were initially referred for liver-small bowel transplantation. CONCLUSIONS: This preliminary experience suggests that PN-dependent patients with advanced liver dysfunction in the setting of the short bowel syndrome may, in some instances, experience functional and biochemical liver recovery. The latter appears to parallel autologous gut salvage in most cases. As a corollary, the authors believe that even advanced degrees of liver dysfunction should not preclude attempts at autologous gut salvage in very carefully selected patients. Such a policy of "aggressive conservatism" may help avoid the need for liver/intestinal transplantation in some patients who appear to be not responding to PN.

Allergic disorders of the gastrointestinal tract.

Allergic disorders of the gastrointestinal tract were once thought of as primarily dermatological manifestations of common food allergens such as peanuts. Recently, greater attention to these products has arisen as complex mechanisms of action have been more clearly delineated. Specific disease states have recently been recognized associated with gastrointestinal reactions to foods, such as celiac disease, infantile formula protein intolerance, and eosinophilic gastroenteritis have been well described. More recently, eosinophilic esophagitis and allergic constipation have been described. This article will review current information regarding the commonly identified gastrointestinal allergic states, and more detailed information regarding two new allergic entities will also be described.

Randomized clinical trial of soy formula with and without added fiber in antibiotic-induced diarrhea.

OBJECTIVE: The objective of this study was to examine the effects of soy formulas with and without added soy fiber in children who developed diarrhea while receiving antibiotics. DESIGN: In a masked, randomized parallel study, older infants and toddlers were fed commercial soy formulas with or without added soy fiber for 10 days on occurrence of diarrhea during the administration of antibiotics. Subjects were stratified by feeding (formula versus cow's milk). The primary variables were duration of diarrhea, stool characteristics, and intake. Secondary variables were weight and spit-up. RESULTS: All 45 children who completed the 10-day study received >30% of their caloric intake from formula. Fiber intake from other foods did not differ between groups and averaged 0.5 g/day. Total median fiber intake of the group fed the formula with added fiber was 6.53 g/day. The mean duration of diarrhea was 25.1 +/- 5.2 hours for children fed the formula with added fiber and 51.6 +/- 10.7 hours for those fed the regular formula (P =.0013). CONCLUSION: The duration of antibiotic-induced diarrhea in children fed the soy formula with added soy fiber was significantly reduced.

The role of eicosanoids in the process of adaptation following massive bowel resection in the rat.

BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) stimulate intestinal adaptation. Prostaglandins also enhance intestinal adaptation. The purpose of this study was to determine by which eicosanoid pathway dietary arachidonic acid enhances intestinal adaptation. Cyclo-oxygenase or lipoxygenase were selectively inhibited to determine whether either of them enhanced or inhibited adaptation. METHODS: Sixty Sprague-Dawley rats were divided into 2 groups, one receiving an 80% small bowel resection and the other receiving a sham operation. Rats were further divided into groups receiving either a placebo, a general lipoxygenase inhibitor (nordihydroguaiaretic acid [NDGA] at 40 mg/kg per day), or a cyclo-oxygenase-2 inhibitor (Etodolac at 3 mg/kg per day). Rats were pair-fed a diet containing 30% kcal from fat, primarily consisting of AA. RESULTS: After 14 days, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining small intestine. There was a significant decrease in ileal mucosal mass in rats receiving Etodolac and a significant increase in mucosal mass in the duodenum in rats receiving NDGA (both p < .001). Mucosal DNA, protein, and disaccharidase data showed similar trends. CONCLUSIONS: These findings suggest that after small bowel resection, dietary arachidonic acid may facilitate the adaptation process by acting as a substrate for the synthesis of prostaglandins, and not through the derivatives of lipoxygenase such as leukotrienes or thromboxanes.

Saccharomyces boulardii does not stimulate mucosal hyperplasia after intestinal resection in the rat.

BACKGROUND: Polyamines have been shown to be important regulators of the intestinal adaptation process after massive bowel resection. Saccharomyces boulardii is yeast that has the ability to synthesize polyamines. Therefore. S. boulardii may be useful in the treatment of short bowel syndrome. METHODS: Twenty 150-g male Sprague-Dawley rats were subjected to 80% jejunoileal resection. Another 20 animals received transection and closure and served as pair fed controls. One half of the resected rats and one half of the controls were given S. boulardii 25 mg/day. RESULTS: After 2 weeks, mucosal mass (mg/cm bowel) did not differ between treated and non-treated animals despite the presence of a marked resection effect. Mucosal DNA, protein, and sucrase activity likewise did not differ. Subsequently, the experiment was repeated four times the original dose (100 mg/day) and found comparable results. In the proximal bowel, mucosal mass was 92+/-6 mg/cm in treated animals versus 107+/-8 mg/cm in untreated rats. In the distal small bowel, comparable values were 85+/-5 mg/cm and 88+/-4 mg/cm. Again, mucosal DNA, protein, and sucrase activity levels paralleled these results. CONCLUSIONS: Although S. boulardii may stimulate polyamine synthesis, it does not seem to be helpful in augmenting gut adaptation in this animal model of short bowel syndrome.

Probiotics: future directions.

Clinical studies have shown that certain probiotics may be useful in treating a variety of diarrheal disorders, including rotavirus diarrhea, antibiotic-associated diarrhea, Clostridium difficile diarrhea, and traveler's diarrhea. New data suggest that probiotics might be useful in controlling inflammatory diseases, treating and preventing allergic diseases, preventing cancer, and stimulating the immune system, which may reduce the incidence of respiratory disease. Different modes of administering probiotics are currently being investigated, which may ultimately lead to the widespread use of probiotics in functional foods. It is important that such practices be directed by carefully controlled clinical studies published in peer-reviewed journals.

Enteral nutrition in short bowel syndrome.

Enteral nutrition in pediatric short bowel syndrome is a key component in facilitating a child's growth and development. In addition, aggressive use of enteral nutrition is not only one of the most important factors in promoting intestinal adaptation; it as well avoids the numerous complications associated with long-term parenteral nutrition. This manuscript will review the appropriate enteral nutrition for a child with short bowel syndrome. Issues to be addressed include appropriate enteral formula selection, solid food intake, enteral administration routes, and devices. Information presented is based on current research as well as experience with a large population of pediatric short bowel syndrome patients.

The role of probiotics in the treatment of intestinal infections and inflammation.

Clinical studies have established that certain probiotics are useful in a variety of intestinal disorders, including viral diarrhea, antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and traveler's diarrhea. Evolving data suggest that probiotics might be useful in the control of inflammatory diseases, treatment and prevention of allergic diseases, cancer prevention, and stimulation of the immune system, which may result in the reduction in respiratory disease. A review of current data regarding the most common probiotics is presented. It is important that probiotic use be directed by well-designed, placebo-controlled clinical studies published in peer-reviewed journals.

Isolated intestinal transplantation for intestinal failure.

OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal failure. However, some experience life-threatening complications from parenteral nutrition, and in these individuals intestinal transplantation may be lifesaving. METHODS: This is a retrospective review of 28 consecutive isolated small bowel transplants performed in eight adults and 20 children between December 1993 and June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient and graft survivals were 93% and 71%, respectively. The causes of graft loss were hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n = 1), and patient death (n = 1). The median length of time required until full enteral nutrition was 27 days. All 28 patients have experienced acute rejection of their small bowel grafts and rejection led to graft failure in five. Jaundice and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and hyperbilirubinemia was completely reversed in all patients with functional grafts within 4 months of transplantation. Three patients developed post-transplant lymphoproliferative disease (11%). Three recipients developed cytomegalovirus enteritis and all were successfully treated. CONCLUSIONS: Patient survival after intestinal transplantation is comparable to parenteral nutrition for patients with intestinal failure. Better immunosuppressive regimens are needed to decrease the risk of graft loss from acute rejection. The incidence of posttransplant lymphoproliferative disorder is higher after intestinal transplantation than after other solid organ transplants and the risk of cytomegalovirus enteritis is low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the absence of established cirrhosis can be reversed.

Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children.

OBJECTIVE: The objective of this study was to determine the efficacy of Lactobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the incidence of antibiotic-associated diarrhea when coadministered with an oral antibiotic in children with acute infectious disorders. STUDY DESIGN: Two hundred two children between 6 months and 10 years of age were enrolled; 188 completed all phases of the protocol. LGG, 1 x 10(10) - 2 x 10(10) colony forming units per day, or comparable placebo was administered in a double-blind randomized trial to children receiving oral antibiotic therapy in an outpatient setting. The primary caregiver was questioned every 3 days regarding the incidence of gastrointestinal symptoms, predominantly stool frequency and consistency, through telephone contact by blinded investigators. RESULTS: Twenty-five placebo-treated but only 7 LGG-treated patients had diarrhea as defined by liquid stools numbering 2 or greater per day. Lactobacillus GG overall significantly reduced stool frequency and increased stool consistency during antibiotic therapy by the tenth day compared with the placebo group. CONCLUSION: Lactobacillus GG reduces the incidence of antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections.

Enteral and parenteral nutrition in patients with short-bowel syndrome.

Short-bowel syndrome is functionally defined as a state of malabsorption following loss of small bowel. Most cases occur in the neonatal period after extensive resection for necrotizing enterocolitis, or due to congenital anomalies of the gastrointestinal tract. A smaller percentage originate later in life from surgical treatment of Crohn's disease, neoplastic disorders, or vascular events. The physiological, morphological and functional intestinal gradient determines the clinical picture leading to better tolerance of jejunal than ileal resections. The subsequent adaptation process requires enteral feeding with a different impact of specific nutrients, and is also influenced by a number of humoral mediators such as enteroglucagon, gastrin, growth factors, prostaglandins and polyamines. Nutritional management starts parenterally via a central venous line covering basic demands, substituting current losses and restoring pre-existing deficiencies. Continuous enteral tube feeding is added as soon as postoperative ileus resolves, beginning with an elemental diet, which is gradually increased first in concentration, then in quantity, and supplemented by small oral meals. Cycling of parenteral nutrition is the next step. As soon as sufficient stability is reached, the child should be discharged home under continued outpatient care. Main long-term problems comprise bacterial overgrowth, fluid and electrolyte disequilibration, nutritional deficiencies, parenteral nutrition-related liver disease, and central venous line complications such as sepsis and thrombosis.

Dietary lipids influence intestinal adaptation after massive bowel resection.

BACKGROUND: Certain lipids, primarily long chain fatty acids and especially long chain polyunsaturated fatty acids (LCPUFAs) from marine oils, stimulate gut adaptation after resection. The goal of this study was to define the degree of resection that provides an optimal model for adaptation and to determine if dietary LCPUFAs improve intestinal adaptation after resection. METHODS: One hundred and fifty-g male Sprague-Dawley rats were divided into groups receiving 60%, 70%, and 80% bowel resection. After resection, each group was subdivided into two dietary groups and pair fed diets containing either safflower oil or docosahexaenoic acid (DHA) and arachidonic (AA). RESULTS: After 2 weeks, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining intestine. Rats receiving 80% resection responded with the highest level of intestinal adaptation. Within the 80% resection group, diet containing DHA and AA stimulated adaptation significantly more than safflower diet. A second study further evaluated the effect on LCPUFAs on intestinal adaptation. Diets included a control group 10% soy oil, and three diets differing in their AA-DHA fat blend ratio at 5% AA and 3.3% DHA, 15% AA and 10% DHA, and 45% AA and 30% DHA. The addition of LCPUFAs to diets enhanced intestinal adaptation in a linear, dose-dependent manner after an 80% small bowel resection. Rats fed a diet containing 30% DHA-45% AA had significantly enhanced mucosal mass compared to rats fed a diet containing 10% soy oil, and considerably higher compared to rats fed 3.3% DHA-5% AA. CONCLUSIONS: These studies suggest that modification of dietary LCPUFAs may enhance intestinal adaptation in short bowel syndrome.

Chronic diarrhea.

The differential diagnosis of chronic diarrhea varies markedly with age. In infants, it is usually a problem with formula intolerance. Because there is up to a 50% crossover intolerance between milk and soy, the infant should be given an extensively hydrolyzed formula. If such intervention is delayed, he or she may develop intractable diarrhea of infancy. Most affected toddlers have either irritable colon of infancy or protracted viral enteritis with low-grade mucosal injury and are consuming hypertonic feedings. In either case, institution of a high-fat, low-carbohydrate diet that includes whole milk often results in significant improvement. Dietary lactose rarely is a problem. A likely cause of diarrhea among children and adolescents is inflammatory bowel disease. With the exception of toddlers, chronic diarrhea suggests the presence of significant organic disease.

Increasing oral fluids in chronic constipation in children.

Increasing the amount and type of fluid intake in children with simple constipation remains a common intervention recommended by both the medical profession and lay consumers. Efforts to increase overall water intake and/or high osmolarity liquid intake have no research or physiological basis that would result in softer and/or more frequent stools. The purpose of this project was to identify whether an effect on stooling characteristics would be noted with a concerted effort to increase liquid intake.