Probiotics are referred to as live microorganisms and also have been proven to have a health effect on hosts at the proper dose. of studies, including digestive systemic diseases (gastrointestinal diseases and hepatic diseases), obesity and diabetes, allergic diseases, nervous systemic diseases, atherosclerosis, bone diseases, and female reproductive systemic diseases. (subspecies ((subspecies are forecasted to code most of the defense systems. The gene clusters of are forecasted to code tight adherence pili in order to promote intestinal barrier integrity, and the genomes of are predicted to encode signaling proteins[2]. VSL#3 has a protective effect on intestinal barrier function (IBF), which is one of the important functions for treating multiple chronic diseases. This article provides insight into the physiological characteristics of VSL#3 and its involvement in the treatment of chronic diseases. Furthermore, we review the results from a large number of basic and clinical studies about digestive systemic diseases and the use of VSL#3 for other systemic diseases (Physique ?(Figure1),1), which are indicative of future directions for VSL#3-based therapy. VSL#3 is usually a kind of formula probiotic with sufficient evidence-based medical evidence in some digestive systemic diseases, but evidence is usually insufficient in many other systemic diseases. We need to observe whether VSL#3 is effective in these diseases in the future. Open in a separate window Physique 1 The types of disease for which VSL#3 can work. AAD: Antibiotic-associated diarrhea; CID: Chemotherapy-induced diarrhea; IBS: Irritable bowel syndrome; CBP: Chronic bacterial prostatitis; CP: Chronic prostatitis; CPPS: Chronic pelvic pain syndrome; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohns disease; MC: Microscopic colitis; FAP: Familial adenomatous polyposis; NAFLD: Non-alcoholic fatty liver disease; ALD: Alcoholic liver organ disease; HE: Hepatic encephalopathy; AS: Atherosclerosis. RAMIFICATIONS OF VSL#3 ON IBF Many factors have already been discovered to lead to IBF: The mechanised hurdle, biological hurdle, Elaidic acid chemical hurdle, and immune system hurdle. The consequences of VSL#3 on IBF are shown in Figure ?Physique22. Open in a separate window Physique 2 Effects of VSL#3 on intestinal barrier function. VSL#3 acts around the four components of the intestinal barrier: The mechanical barrier, biological barrier, chemical barrier, and immune barrier. In terms of Elaidic acid the mechanical barrier, VSL#3 can increase occludin and zonula occludens-1 and decrease claudin-2 in order to improve tight ABP-280 junction protein function, and the effect is achieved by increasing the activity of T-cell protein tyrosine phosphatase, which is able to decrease T-cell protein tyrosine phosphatase-dependent interferon- signaling and increase transepithelial electrical resistance[5-7]. VSL#3 can increase transepithelial electrical resistance by activating the mitogen-activated protein kinase p42/44 and p38 pathway[9]. In terms of the biological barrier, VSL#3 can increase the amount of intestinal commensal bacteria and decrease the amount of fungi[12]. In terms of the chemical barrier, VSL#3 can increase and gene expression to regulate mucus secretion[9]. In terms of the immune barrier, VSL#3 can inhibit the proinflammatory nuclear factor-B (NF-B) pathway, such as inducing heat shock protein (HSP) and reducing monocyte chemoattractant protein-1 (MCP-1). The action mechanism is the early inhibition of proteasome by generating soluble factors[21]. VSL#3 also up-regulates the peroxisome proliferator-activated receptor (PPAR) signaling pathway to antagonize the NF-B pathway[32]. An appropriate dose of VSL#3 can induce the maturation of dendrite cells (DC)[27,28], and VSL#3 can inhibit interferon-inducible protein-10 (IP-10) in intestinal epithelial cells (IEC)[22-24] and the lipopolysaccharide (LPS)-induced expression of chemokines (CXCL9, CXCL10, CCL2, CCL7, and CCL8) by inhibiting STAT-1 phosphorylation[27]. VSL#3 is also able to decrease interleukin (IL)-12 (p40) production induced by LPS[30]. Moreover, VSL#3 can induce IL-10 produced by DC and decrease the influx of innate immune cells (CD11b+) and adaptive immune cells (CD4+/CD8+)[30,31]. The down-regulation of the signaling pathway of Toll-like receptors (TLR) by VSL#3 also has benefits for the intestinal immune barrier[32]. IEC: Intestinal epithelial cells; ZO-1: Zonula occludens-1; TCPTP: T-cell protein tyrosine phosphatase; IFN-: Interferon-; TER: Transepithelial electrical resistance; MAPK: Mitogen-activated protein kinase; GALT: Gut-associated lymphoid tissue; IEL: Intraepithelial lymphocytes; LPL: Lamina propria lymphocytes; sIgA: secreted immunoglobulin A; NF-B: Nuclear factor-B; IL: Interleukin; MCP-1: Monocyte chemoattractant protein-1; HSP: Warmth shock protein; PPAR: Peroxisome proliferator-activated receptor ; IP-10: Interferon-inducible protein-10; DC: Dendrite cells; LPS: Lipopolysaccharide; TLR: Toll-like receptors. Effects of VSL#3 Elaidic acid on mechanical barrier function The mechanical barrier is mainly comprised of intestinal epithelial cells (IEC) and the protein networks between IEC, including desmosomes, adherent junctions, and tight junctions. Tight junctions maintain epithelial polarity and regulate selective paracellular.