Probiotics are widely used by patients with Crohn's disease (CD) in an attempt to improve their health, but few controlled studies have been done to evaluate the efficacy of these therapies. We conducted a randomized, placebo-controlled trial of the probiotic Lactobacillus rhamnosus strain GG (LGG) to see if the addition of LGG to standard therapy prolonged remission in children with CD. Concomitant medications allowed in the study included aminosalicylates, 6-mercaptopurine, azathioprine, and low-dose alternate day corticosteroids. Seventy-five children (age range, 5-21 yr) with CD in remission were randomized to either LGG (n=39) or placebo (n=36) and followed for up to 2 years. The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group (P=0.24); 31% (12/39) of patients in the LGG group developed a relapse compared with 6/36 (17%) of the placebo group (P=0.18). The LGG was well tolerated, with a side effect profile comparable with placebo. This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to standard therapy.
ASO-OCCLUSION IS ONE OF THE hallmarks and major complications of sickle cell disease (SCD), resulting in acute debilitating episodic pain and contributing to infection, acute chest syndrome, splenic sequestration, stroke, acute and chronic multisystem organ damage, and shortened life expectancy. Acute painful vaso-occlusive crisis (VOC) is one of the earliest manifestations of SCD, with crises often beginning in infancy. 1,2 Beyond early childhood, VOC accounts for 90% of hospitalizations in children with SCD. The pathophysiology of vasoocclusion is complex and not fully understood. Polymerization of deoxygenated hemoglobin S (HbS) produces sickled cells that result in vasoocclusion. In addition, abnormal interactions between poorly deformable HbS and vascular endothelium result in dysregulation of vascular tone 3-5 ; activation of monocytes, 6 adhesion molecules, 7 and procoagulant factors 8 ; and reperfusion injury. 9 These vascular disturbances increase red blood cell transit time, prolonging deoxygenation, which promotes further sickling and vaso-occlusion. Despite advances in understanding of SCD including identification of potential targets for therapy, to date there are no effective, approved mechanismof-disease-based therapies for acute VOC, and symptom-directed therapies (ie, analgesia and fluids) with
A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion.
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