关键词: 重大慢性疾病, 微生态疗法, 益生元, 益生菌, 粪菌移植, 工程益生菌, 人工合成菌群

Abstract:

The pool of microbes inhabiting our gut is known as ‘gut microbiota’. The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis, and its structure and function have changed significantly since the industrialization era, especially with the change of lifestyle and the improvement of health care. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life. Dysbiosis of the gut microbiome is caused by an imbalance between the commensal and pathogenic microbiomes, and alterations of the intestinal microbiota can be directly correlated with several diseases. This remodeled ‘industrialized’ gut microbiota has a profound impact on human health, accelerating the development of major chronic diseases such as digestive, metabolic and psychiatric disorders. Therefore, correcting intestinal microecological imbalance has become one of the core strategies to address the challenges in the development of major chronic non-communicable diseases. However, only a few conventional gut microbiome therapeutics developed to target the regulation of intestinal flora structure and function, such as probiotic therapy and fecal transplantation therapy have been used for the prevention and treatment of major chronic diseases with multiple intractable clinical conditions. Moreover, safety issues such as poor controllability and unclear genetic background of the flora have emerged. The iterative development of synthetic biology and microbial culture omics technology tools have promoted the development of novel microecological drugs, which have become the key to the precise identification and effective administration of major chronic diseases. This review takes the perspective of intervention and treatment of major chronic diseases such as digestive diseases, metabolic diseases and psychiatric diseases. The research progress of synthetic biology concepts and related technologies in designing and constructing engineered probiotics is systematically discussed. The application of microbiome therapeutics focusing on engineered probiotics in 3 categories of major chronic diseases is further reviewed. Moreover, we summarize the opportunities and challenges of using engineered probiotics to build synthetic flora, aiming to providing new methods and strategies for the diagnosis and prevention of major chronic diseases, thus promoting technological innovation and development of gut microbiome therapeutics.

Key words: major chronic diseases, microecological therapy, prebiotics, probiotics, fecal microbiota transplant, engineered probiotic, synthetic microbial community