2021 Vol. 12, No. 5

The microbiome is closely linked to human health and disease, making it a fast-growing research field full of translational potential. Inspired by the famous ancient painting "Along the River During the Qingming Festival" (also known by its Chinese name as the "Qingming Shanghe Tu"), the cover picture depicts that harmonious colonization of microbes inside the human gut is critical to the normal function of the gastrointestinal tract and even beyond.

A practical guide to amplicon and metagenomic analysis of microbiome data
Yong-Xin Liu, Yuan Qin, Tong Chen, Meiping Lu, Xubo Qian, Xiaoxuan Guo, Yang Bai
2021, 12(5): 315-330. doi: 10.1007/s13238-020-00724-8
Advances in high-throughput sequencing (HTS) have fostered rapid developments in the field of microbiome research, and massive microbiome datasets are now being generated. However, the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field. Here, we systematically summarize the advantages and limitations of microbiome methods. Then, we recommend specific pipelines for amplicon and metagenomic analyses, and describe commonly-used software and databases, to help researchers select the appropriate tools. Furthermore, we introduce statistical and visualization methods suitable for microbiome analysis, including alpha- and betadiversity, taxonomic composition, difference comparisons, correlation, networks, machine learning, evolution, source tracing, and common visualization styles to help researchers make informed choices. Finally, a stepby-step reproducible analysis guide is introduced. We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.
The microbiome in inflammatory bowel diseases: from pathogenesis to therapy
Sheng Liu, Wenjing Zhao, Ping Lan, Xiangyu Mou
2021, 12(5): 331-345. doi: 10.1007/s13238-020-00745-3
Inflammatory bowel disease (IBD) has become a global disease with accelerating incidence worldwide in the 21st century while its accurate etiology remains unclear. In the past decade, gut microbiota dysbiosis has consistently been associated with IBD. Although many IBDassociated dysbiosis have not been proven to be a cause or an effect of IBD, it is often hypothesized that at least some of alteration in microbiome is protective or causative. In this article, we selectively reviewed the hypothesis supported by both association studies in human and pathogenesis studies in biological models. Specifically, we reviewed the potential protective bacterial pathways and species against IBD, as well as the potential causative bacterial pathways and species of IBD. We also reviewed the potential roles of some members of mycobiome and virome in IBD. Lastly, we covered the current status of therapeutic approaches targeting microbiome, which is a promising strategy to alleviate and cure this inflammatory disease.
Gut microbes in cardiovascular diseases and their potential therapeutic applications
Ling Jin, Xiaoming Shi, Jing Yang, Yangyu Zhao, Lixiang Xue, Li Xu, Jun Cai
2021, 12(5): 346-359. doi: 10.1007/s13238-020-00785-9
Microbial ecosystem comprises a complex community in which bacteria interact with each other. The potential roles of the intestinal microbiome play in human health have gained considerable attention. The imbalance of gut microbial community has been looked to multiple chronic diseases. Cardiovascular diseases (CVDs) are leading causes of morbidity worldwide and are influenced by genetic and environmental factors. Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome. In this review, we highlight the complex interplay between microbes, their metabolites, and the potential influence on the generation and development of CVDs. The therapeutic potential of using intestinal microbiomes to treat CVD is also discussed. It is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.
The role of the gut microbiome and its metabolites in metabolic diseases
Jiayu Wu, Kai Wang, Xuemei Wang, Yanli Pang, Changtao Jiang
2021, 12(5): 360-373. doi: 10.1007/s13238-020-00814-7
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.
Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma
Wei Jia, Cynthia Rajani, Hongxi Xu, Xiaojiao Zheng
2021, 12(5): 374-393. doi: 10.1007/s13238-020-00748-0
Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are the second and third most common causes of death by cancer, respectively. The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol, smoking, diet, obesity and diabetes. Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC. However, the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors. In this review, we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC. Based on the idea that the gut microbiota are an additional “lifeline” and contribute to the tumor microenvironment, we can observe from previously published literature how the microbiota can cause a shift in the balance from normal → inflammation → diminished inflammation from early to later disease stages. This pattern leads to the hypothesis that tumor survival depends on a less proinflammatory tumor microenvironment. The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.
Role of gut microbiota in identification of novel TCM-derived active metabolites
Tzu-Lung Lin, Chia-Chen Lu, Wei-Fan Lai, Ting-Shu Wu, Jang-Jih Lu, Young-Mao Chen, Chi-Meng Tzeng, Hong-Tao Liu, Hong Wei, Hsin-Chih Lai
2021, 12(5): 394-410. doi: 10.1007/s13238-020-00784-w
Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.
Targeting the alternative bile acid synthetic pathway for metabolic diseases
Wei Jia, Meilin Wei, Cynthia Rajani, Xiaojiao Zheng
2021, 12(5): 411-425. doi: 10.1007/s13238-020-00804-9
The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (producing the 12α-hydroxylated primary BA, cholic acid), and the alternative pathway (producing the non-12α-hydroxylated primary BA, chenodeoxycholic acid). BA synthesis and excretion is a major pathway of cholesterol and lipid catabolism, and thus, is implicated in a variety of metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease. Additionally, both oxysterols and BAs function as signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways in various tissues, regulating glucose, lipid homeostasis, inflammation, and energy expenditure. Modulating BA synthesis and composition to regulate BA signaling is an interesting and novel direction for developing therapies for metabolic disease. In this review, we summarize the most recent findings on the role of BA synthetic pathways, with a focus on the role of the alternative pathway, which has been under-investigated, in treating hyperglycemia and fatty liver disease. We also discuss future perspectives to develop promising pharmacological strategies targeting the alternative BA synthetic pathway for the treatment of metabolic diseases.
Unexpected guests in the tumor microenvironment: microbiome in cancer
Abigail Wong-Rolle, Haohan Karen Wei, Chen Zhao, Chengcheng Jin
2021, 12(5): 426-435. doi: 10.1007/s13238-020-00813-8
Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.