Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial transloc...Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.展开更多
Colorectal cancer （CRC） is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that ...Colorectal cancer （CRC） is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that the gut microbiota is a new and important player in the development of CRC. Imbalance of the gut microbiota, especially dysregulated gut bacteria, contributes to colon cancer through mechanisms of inflammation, host defense modulations, oxidative stress, and alterations in bacterial-derived metabolism. Gut commensal bacteria are anatomically defined as four populations： luminal commensal bacteria, mucus-resident bacteria, epithelium-resident bacteria, and lymphoid tissue-resident commensal bacteria. The bacterial flora that are harbored in the gastrointestinal （GI） tract vary both longitudinally and cross-sectionally by different anatomical localization. It is notable that the translocation of colonic commensal bacteria is closely related to CRC progression. CRC-associated bacteria can serve as a noninvasive and accurate biomarker for CRC diagnosis. In this review, we summarize recent findings on the oncogenic roles of gut bacteria with different anatomical localization in CRC progression.展开更多
基金Supported by Immuron, Nasvax, Plantylight, Desert Labs,Teva Pharmaceutical and ENZO Biochem
文摘Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.
基金This project was supported by RGC-GRF Hong l（ong （766613, 14106145）, the National Basic Research Program of China （2013CB531401）, the National Natural Science Foundation of China （NSFC） （81201963, 81372600）, the Shenzhen Municipal Science and Technology R＆D fund （JCYJ20120619152326450）, and the Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.
文摘Colorectal cancer （CRC） is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that the gut microbiota is a new and important player in the development of CRC. Imbalance of the gut microbiota, especially dysregulated gut bacteria, contributes to colon cancer through mechanisms of inflammation, host defense modulations, oxidative stress, and alterations in bacterial-derived metabolism. Gut commensal bacteria are anatomically defined as four populations： luminal commensal bacteria, mucus-resident bacteria, epithelium-resident bacteria, and lymphoid tissue-resident commensal bacteria. The bacterial flora that are harbored in the gastrointestinal （GI） tract vary both longitudinally and cross-sectionally by different anatomical localization. It is notable that the translocation of colonic commensal bacteria is closely related to CRC progression. CRC-associated bacteria can serve as a noninvasive and accurate biomarker for CRC diagnosis. In this review, we summarize recent findings on the oncogenic roles of gut bacteria with different anatomical localization in CRC progression.
