The role of the gut microbiome and its metabolites in metabolic diseases

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Protein & Cell

REVIEW The role of the gut microbiome and its metabolites in metabolic diseases Jiayu Wu1,2,3, Kai Wang1,2,3, Xuemei Wang1,2,3, Yanli Pang1, Changtao Jiang1,2,3& Department of Obstetrics and Gynecology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Third Hospital, Peking University, Beijing 100191, China 2 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China 3 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China & Correspondence: [email protected] (C. Jiang) Received May 3, 2020 Accepted November 10, 2020

ABSTRACT It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases, while in recent years, accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular disease and so on. Numerous microorganisms dwell in the gastrointestinal tract, which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances, thus acting as a link between the gut microbiome and its host. The gut microbiome is shaped by host genetics, immune responses and dietary factors. The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases. Therefore, targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future. This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases. Furthermore, recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.

KEYWORDS gut microbiome, metabolism, metabolite, immune regulation, metabolic diseases

© The Author(s) 2020

INTRODUCTION The worldwide prevalence of metabolic diseases, including obesity, nonalcoholic fatty liver disease (NAFLD), insulin resistance, type 2 diabetes mellitus (T2DM), atherosclerosis (AS) and polycystic ovary syndrome (PCOS), has grown dramatically (Norman et al., 2007; Popkin et al., 2012; Younossi et al., 2016; Zheng et al., 2018; Virani et al., 2020). Over the past few decades, the increasing consumption of high-calorie foods and displacement of leisure-time physical activities with sedentary activities has ultimately resulted in a positive energy balance (where energy intake exceeds energy expenditure), and these have become the main risk factors for obesity and obesity-related diseases (Heymsfield and Wadden, 2017). In this situation, the adipose tissue exceeds its ability to store all the excess energy as triglycer