The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotictreated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.H epatocellular carcinoma (HCC) is one of the most common cancers, the sixth most common neoplasm, and the second most deadly type of cancer worldwide (1). The traditional HCC treatment, including surgical treatment, local ablation therapy, and chemotherapy, could offer potential cure, yet patients are facing many limitations including the poor hepatic reserve. HCC is clearly a disease for which alternative therapeutic strategies must be developed. A better understanding of the interactions between cancer cells and stromal components in the tumorassociated proinflammatory microenvironment would be important for the management of this disease.The tumor microenvironment is infiltrated with various immune cells such as T cells, macrophages, neutrophils, natural killer (NK) cells, and myeloid-derived suppressor cells. Inflammation is known to play a pivotal role in tumor development by escalating tumor angiogenesis and cell growth. Once a solid tumor is formed, inflammation arises in the tumor-promoting direction. At the same time, new vasculature is needed in the tumor to provide nutrients and oxygen to support the growth of cancer cells, and this process plays a critical role in HCC, a highly vascularized tumor (2). Inflammation and angiogene...

Highlights d A high variability in glycemic response to exercise in subjects with prediabetes exists d Responders and non-responders exhibit differential alterations of the gut microbiota d Gut microbiota from responders confers the metabolic benefits of exercise in mice d Baseline microbiome features accurately predict personalized exercise responses

The full-genome sequencing of the filamentous fungi Aspergillus nidulans, Aspergillus niger, and Aspergillus oryzae has opened possibilities for studying the cellular physiology of these fungi on a systemic level. As a tool to explore this, we are making available an Affymetrix GeneChip developed for transcriptome analysis of any of the three above-mentioned aspergilli. Transcriptome analysis of triplicate batch cultivations of all three aspergilli on glucose and xylose media was used to validate the performance of the microarray. Gene comparisons of all three species and crossanalysis with the expression data identified 23 genes to be a conserved response across Aspergillus sp., including the xylose transcriptional activator XlnR. A promoter analysis of the upregulated genes in all three species indicates the conserved XlnRbinding site to be 5-GGNTAAA-3. The composition of the conserved gene-set suggests that xylose acts as a molecule, indicating the presence of complex carbohydrates such as hemicellulose, and triggers an array of degrading enzymes. With this case example, we present a validated tool for transcriptome analysis of three Aspergillus species and a methodology for conducting cross-species evolutionary studies within a genus using comparative transcriptomics.Aspergillus nidulans ͉ Aspergillus niger ͉ Aspergillus oryzae ͉ XlnR