Comprehensive analyses reveal the effects of gut microbiome to anti-obesity and anti-cancer

Abstract

The importance of the gut microbiome in human health such as obesity and cancer is still increasing. Here, we report that the roles and effects of gut microbiome for anti-obesity and anti-cancer. As part I, we investigated the anti-obesity microbiome. 16S ribosomal RNA (rRNA) sequencing of stools from participants was used for identifying the gut microbiome associated to anti-obesity. We observed that abundance of Bifidobacterium longum and Bifidobacterium bifidum were negatively associated to with visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis showed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum could protect against diet-induced obesity. We, then, administered Bifidobacterium longum and Bifidobacterium bifidum mice fed with high-fat diet and observed that enhanced bile acid signaling to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and alleviation in hepatic steatosis and glucose homeostasis. Oral treatment of Bifidobacterium longum and Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice, when brown fat cell differentiation was increased in specific-pathogen free (SPF) mice. As part II, we investigated the anti-cancer microbiome. To demonstrate microbiome-induced immune activity, we have performed 16S rRNA sequencing of stools from cancer patients who treated with immunotherapy and fecal microbiome transplantation (FMT). We observed that clinical benefit from one hepatocellular carcinoma patient as improve to partial response from progressive disease. We also observed FMT treatments from different donors were associated to a responsiveness to anti-PD-1 treatment. Profiling of human immune system and microbiome showed that response was accompanied with increment of cytotoxic T cell in blood and tumor environment, immune cytokines, and relative abundance of Prevotella stercorea (P. stercorea). Indeed, the treatment of P. sterocrea induced human CD4+ and CD8+ activity and increased IFN-γ secretion in CD8+ T cells. Administration of P. sterocrea suppressed tumor growth enhancing tumor-infiltrated cytotoxic T cells in syngeneic mouse model. An additional clinical data showed gut microbiome at baseline of immunotherapy was able to predict the best response to immunotherapy. Finally, our findings suggest that certain gut microbiome could be used in therapeutic applications for anti-obesity or anti-cancer treatments.