Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Abstract

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...

658 Marine Omega-3 Polyunsaturated Fatty Acid Intake and Survival After Colorectal Cancer Diagnosis

“…First, data on cancer recurrence were unavailable. Nevertheless, because the median survival for metastatic CRC was approximately 10 to 12 months during much of the period of this study, [38] CRCspecific mortality should be a reasonable surrogate for cancer-specific outcomes. Second, treatment data are not collected in the cohorts.…”

Sustainable therapies by engineered bacteria

“…Many studies have shown the relationship between microbiome dysbiosis and disease, such as infections, inflammation, allergy, asthma, obesity, cancer and even neurological disorders (Sekirov et al ., 2010; Carding et al ., 2015; Li et al ., 2016; Foo et al ., 2017). Therefore, it is reasonable to think that interventions on the microbiome with specific microorganisms will allow the development of therapies for such diseases (Lemon et al ., 2012).…”

Microbiote intestinal et réponses aux thérapies anti-tumorales

“…Ces probiotiques ralentissent la croissance tumorale en réduisant notamment le recrutement des lymphocytes Th17 intestinaux producteurs d'IL-17 dans la tumeur et l'angiogenèse. La capacité de ce cocktail probiotique à moduler la composition du microbiote intestinal, caractérisée notamment par un enrichissement en Prevotella et Oscillibacter, bactéries reconnues pour leur capacité à produire des métabolites anti-inflammatoires et à réduire la polarisation Th17, a été également montrée [37]. Le potentiel du microbiote est d'ores et déjà utilisé en clinique pour le traitement des infections récurrentes à Clostridium difficile (CDI).…”