Microbiota in Tumors: From Understanding to Application

Abstract

Microbes with complex functions have been found to be a potential component in tumor microenvironments. Due to their low biomass and other obstacles, intratumor microbiota is poorly understood. Mucosal sites and normal adjacent tissues are important sources of intratumor microbiota, while hematogenous spread also leads to the invasion of microbes. Intratumor microbiota affects the progression of tumors through several mechanisms, such as DNA damage, activation of oncogenic pathways, induction of immunosuppression, and metabolization of drugs. Notably, in different types of tumors, the composition and abundance of intratumor microbiota are highly heterogeneous and may play different roles in the progression of tumors. Because of the concern in this field, several techniques such as omics and immunological methods have been used to study intratumor microbiota. Here, recent progress in this field is reviewed, including the potential sources of intratumor microbiota, their functions and related mechanisms, and their heterogeneity. Techniques that can be used to study intratumor microbiota are also discussed. Moreover, research is summarized into the development of strategies that can be used in antitumor treatment and prospects for possible future research in this field.

Keywords: anti-tumor therapy; intratumor microbiota; microbial community heterogeneity; omics technology; source of microbes; tumorigenesis.

Figure 1

History of intratumor microbiota. Major breakthroughs from studies on intratumor microbiota including the discovery, mechanisms, and other achievements.

Figure 2

Sources of intratumor microbiota: A) Mucosal organs. Gut microbes disturb the mucosal barrier and enter tumor sites while intratumor bacteria of pancreatic cancer enter tumor sites through the pancreatic duct. B) NATs. NAT is a potential source of intratumor microbiota. C) Circulatory system. Intratumor microbes enter tumor sites from mouth, gut, tumors and other sites via hematogenous spread.

Figure 3

Mechanisms of intratumor microbiota affecting tumorigenesis and treatment. Two major mechanisms for inducing tumorigenesis include causing DNA damage and activating oncogenic pathways. . Intratumor microbiota also influence anti‐tumor immunity and play complex roles. Moreover, intratumor microbiota metabolize chemotherapeutic drugs and resulting in chemotherapy resistance.

Figure 4

Heterogeneity of intratumor microbiota in different tumors A) Lung tumors. There are several bacteria that influence the progress and metastasis of lung cancers. These bacteria perform their roles using different pathways. B)Gastrointestinal tumors. The composition and function of microbiota in gastrointestinal tumors is complex. Firmicutes, Selenomonas and several other bacteria are closely related to the progression of tumors.

Figure 5

Method to study intratumor microbiota. Detection, identification, and functional analysis are necessary to focus for all research on intratumor microbiota. With the development of culture methods, in vitro and in vivo experiments may provide new insight into this field.

Figure 6

Clinical application of anti‐tumor bacterial treatment strategies. A) Biological agents inducing anti‐tumor immune response. This strategy uses dead or living bacteria to recruit active immune cells like CD8⁺ T cells and therefore initiates anti‐tumor immune response. B) Engineering bacteria inducing anti‐tumor response or used as carriers. Engineering bacteria can be modified to release certain products or conduct certain reactions to inhibit tumors. Also, engineering bacteria can also be used as carriers to carry toxin, immunostimulant, or other drugs.

Figure 7

Prospect of clinical application based on intratumor microbiota. Personalized therapies will be beneficial because of the heterogeneity of intratumor microbiota. Antibiotics and bacterial therapies combined with other anti‐tumor therapies may improve results. Normalizing intratumor microbiota and transplanting certain microorganisms are also potential strategies to enhance the efficiency of anti‐tumor therapies.