Inflammatory bowel disease (IBD) is an emerging health problem associated with the dysregulation of the intestinal immune system and microbiome. Probiotics are able to reduce inflammatory responses in intestinal epithelial cells (IECs). However, entire signaling pathways and the interaction between different probiotics have not been well-documented. This study was designed to investigate the anti-inflammatory effects and mechanisms of single and combined probiotics. HT-29 cells were induced by lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α, treated with Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis or their combination and analyzed for inflammation-related molecules. Both L. acidophilus and B. animalis subsp. lactis reduced interleukin (IL)-8 secretion and the expressions of phosphorylated p65 nuclear factor-kappa B (p-p65 NF-κB), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2), while they increased toll-like receptor 2 (TLR2) expression. L. acidophilus did not decrease intercellular adhesion molecule-1 (ICAM-1) but enhanced the inhibitory efficacy of B. animalis subsp. lactis. Combined probiotics showed the best anti-inflammatory activity. These results suggest that L. acidophilus and B. animalis subsp. lactis may exert a potent anti-inflammatory effect through modulating TLR2-mediated NF-κB and MAPK signaling pathways in inflammatory IECs. Both strains, especially their combination, may be novel adjuvants for IBD therapy.

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A–F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn’s disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed.

Patients with triple-negative breast cancer have few therapeutic strategy options. In this study, we investigated the effect of isoliquiritigenin (ISL) on the proliferation of triple-negative breast cancer cells. We found that treatment with ISL inhibited triple-negative breast cancer cell line (MDA-MB-231) cell growth and increased cytotoxicity. ISL reduced cell cycle progression through the reduction of cyclin D1 protein expression and increased the sub-G1 phase population. The ISL-induced apoptotic cell population was observed by flow cytometry analysis. The expression of Bcl-2 protein was reduced by ISL treatment, whereas the Bax protein level increased; subsequently, the downstream signaling molecules caspase-3 and poly ADP-ribose polymerase (PARP) were activated. Moreover, ISL reduced the expression of total and phosphorylated mammalian target of rapamycin (mTOR), ULK1, and cathepsin B, whereas the expression of autophagic-associated proteins p62, Beclin1, and LC3 was increased. The decreased cathepsin B cause the p62 accumulation to induce caspase-8 mediated apoptosis. In vivo studies further showed that preventive treatment with ISL could inhibit breast cancer growth and induce apoptotic and autophagic-mediated apoptosis cell death. Taken together, ISL exerts an effect on the inhibition of triple-negative MDA-MB-231 breast cancer cell growth through autophagy-mediated apoptosis. Therefore, future studies of ISL as a supplement or alternative therapeutic agent for clinical trials against breast cancer are warranted.

Colorectal cancer is a common cancer strongly associated with diet. Certain probiotics and prebiotics possess an inhibitory activity against colorectal cancer, while synbiotics may be more effective in preventing this cancer than either prebiotics or probiotics alone. Germinated brown rice (GBR) is considered as a candidate prebiotics with anticancer potential. However, the effect of GBR combined with probiotics on colorectal cancer is not clear. The present study investigated the preventive effect of combination of GBR and Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, or both on colorectal carcinogenesis and the possible mechanism in rats treated with 1,2‐dimethylhydrazine (DMH) and dextran sulfate sodium (DSS). DMH/DSS treatment induced preneoplastic aberrant crypt foci (ACF) and mucin‐depleted foci (MDF), reduced superoxide dismutase (SOD) activity, increased anti‐apoptotic Bcl‐2 expression, and decreased the expression of pro‐apoptotic p53, Bax, and caspase‐3 in the colon. Germinated brown rice alone or combined with probiotics inhibited the formation of MDF in the middle colon, enhanced the colonic expression of p53 and Bax, and increased the ratio of Bax/Bcl‐2. Combined treatment of GBR and probiotics inhibited the formation of ACF‐producing sialomucin (SIM‐ACF) and recovered the activity of SOD in the colon. Combination of GBR and L. acidophilus further increased caspase‐3 expression and decreased Bcl‐2 expression. These findings suggest that GBR combined with L. acidophilus and/or B. animalis subsp. lactis may inhibit colorectal carcinogenesis by enhancing antioxidative capacity and inducing apoptosis. This synbiotics may be a potential functional food or chemopreventive agent for controlling colorectal cancer.