This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Whereas bacterial overgrowth is a recognized complication of short gut syndrome there are limited data about intestinal permeability, which also confers risk for bacterial translocation. The potential roles of probiotic therapy for management of bacterial overgrowth and enhancement of altered intestinal permeability have been suggested; however not yet systematically examined in children with short gut syndrome. The hypotheses of this double-blind, randomized cross-over study are: 1) Impaired intestinal permeability and bacterial overgrowth are prevalent in children with short gut syndrome, and 2) Probiotic therapy with Lactobacillus GG will successfully colonize intestinal flora in children with short gut syndrome, 3) Probiotic therapy with Lactobacillus GG is associated with improved intestinal permeability in children with short gut syndrome, and 4) probiotic therapy will enhance the quality of life in children with this syndrome. Patients will be randomized in to two groups as part of a four-week pretest-posttest crossover design. The test measurements will include anthropometry, Hydrogen-breath test for bacterial overgrowth, Lactulose-Mannitol test for intestinal permeability, and quantitative stool cultures for Lactobacillus GG. Half of the patients will be randomly assigned to initial therapy with Lactobacillus GG while the other half will be assigned to an identical placebo. After the posttest measurements have been made, a three-week washout period will occur. During the washout, subjects will discontinue taking the substance (Lactobacillus GG vs. placebo) they were given. At the end of this period, another four-week pretest-posttest phase will be conducted, except that subjects will swap study conditions, i.e., those who originally received therapy with Lactobacillus GG will receive placebo and vice versa. Group assignment will be double blind so that neither the subject nor the researcher will know who is receiving the Lactobacillus GG or placebo.
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