UCC4331 significantly improves in abdominal pain/discomfort, bloating/distension and bowel movements compared with placebo. Our result, cionciding with previous study, showed the possible superiority of Bifidobacterium for treatment in IBS. Lactobacillus acidophilus, in our study, revealed the improvement of barrier function and reduction of cytokines secretion, thus extending for visceral sensitivity. A lot of studies highlighted the properties of different strains of Lactobacillus, mentioning their ability to product the intracolonic short chain fat acid with a consequent improvement in colonic propulsion. However, some of clinical studies are negative and show either no effect or a favorable effect. The divergent results of the efficacy of the Lactobacillus used in IBS could be related to different species and doses, suggesting that the effects of Lactobacillus may be stains-specific. Beyond Bifidobacterium and Lactobacillus, Streptococcus has less frequently been used alone in IBS. Streptococcus faecalis in this study proved to be ineffective in visceral hypersensitivity, gut permeability and immunomodulatory effects. Our results describe metabolic alterations that occur in the progression of PAH from the early to severe stage, where alterations in glucose metabolism through downregulation of glycolysis play an important role. Previous studies, based on hypoxiainduced PH in a relatively earlier/or developing stage of PH animal model describes that the upregulation of hypoxia-induced factor, in combination with HIF-1b, activates over 100 genes involved in metabolism. In particular, there is increased glucose uptake via GLUT1 and GLUT3 as well as inhibition of the pyruvate dehydrogenase complex by pyruvate dehydrogenase kinase that normally oxidizes pyruvate to acetyl-CoA for the Krebs cycle. Other studies have shown that vascular BEZ235 endothelial proliferation in IPAH lesions displays pathological alterations that resemble characteristics of growing tumor cells in cancer. These cells are characterized by the “Warburg effect”, as hyperproliferative tumor cells under hypoxic conditions use aerobic glycolysis with resultant changes in its mitochondrial redox state to escape apoptosis in the developing stage of the PH. Results from previous studies that suggest for increased glycolysis had worked with experimental models of PH at the relatively early stage, such as in vitro studies using smooth muscle cells from animals exposed to 2–3 weeks of hypoxia or in vitro human pulmonary microvascular endothelial cells s transfected with a BMPRII mutation. In several of these studies, PH was induced by experimental measures and studies ICI 182780 focused solely on one cell type, which would ignore possible cellcell interactions that occur in the vascular remodeling process. In contrast to previous studies, our results were obtained from the severe human PAH lung rather than from animal models, which may be the underlying reason for the observation of reduced glycolysis. It remains elusive whether changes in metabolic pathways, for example, the rate of glycolysis, can reflect different stages in the progression of human pulmonary arterial hypertension.