Harness the functions of gut microbiome in tumorigenesis for cancer treatment

Abstract

It has been shown that gut microbiota dysbiosis leads to physiological changes and links to a number of diseases, including cancers. Thus, many cancer categories and treatment regimens should be investigated in the context of the microbiome. Owing to the availability of metagenome sequencing and multiomics studies, analyses of species characterization, host genetic changes, and metabolic profile of gut microbiota have become feasible, which has facilitated an exponential knowledge gain about microbiota composition, taxonomic alterations, and host interactions during tumorigenesis. However, the complexity of the gut microbiota, with a plethora of uncharacterized host-microbe, microbe-microbe, and environmental interactions, still contributes to the challenge of advancing our knowledge of the microbiota-cancer interactions. These interactions manifest in signaling relay, metabolism, immunity, tumor development, genetic instability, sensitivity to cancer chemotherapy and immunotherapy. This review summarizes current studies/molecular mechanisms regarding the association between the gut microbiota and the development of cancers, which provides insights into the therapeutic strategies that could be harnessed for cancer diagnosis, treatment, or prevention.

Keywords: cancer biomarkers; chemotherapy; fecal microbiota transplantation; gut microbiome; immunotherapy; microbiota; probiotics.

FIGURE 1

Bacteria species reside in different types of tumors. The 19 indicated bacteria strains reside in 7 indicated types of tumors [8]. The intratumor bacteria are present in cancer or immune cells such as macrophages (in yellow). These tumor‐associated bacteria may participate in cancer signaling to promote cancer growth. GBM, glioblastoma multiforme

FIGURE 2

Microbial community from colorectal cancer patients promotes carcinogenesis. The stool from patients with colorectal cancer fed into axozymethane (AOM)‐treated mice leads to increased number of polyps. Stool from healthy person is used as a control

FIGURE 3

Impacts of modifying gut microbiota for improving health. Techniques to modulate the gut microbiota: FMT, the administration of defined bacterial species, diet change, the use of probiotics or prebiotics. Effects of each technique in improving health are listed

FIGURE 4

Impacts of bacteria‐derived metabolites on host. Listed bacteria‐derived metabolites and their impacts on affecting host/cancer cell signaling. DCA, deoxycholic acid; SGOC, ser gly one carbon pathway; TAMO, trimethylamine N‐oxide; SCFA, short chain fatty acid; mTOR, the mammalian target of rapamycin; T reg, T regulatory cell; Th1, T helper 1 cell

FIGURE 5

Bacterial strains boost immune responses to fight pathogen infection and enhance anti‐PD‐1 treatment efficacy in cancer. Eleven indicated bacterial strains [132] isolated from healthy human stool samples can induce interferon‐γ‐producing CD8 T cells in the intestine. In mouse models, the 11 strains delivered through FMT can increase interferon‐γ‐producing CD8 T cells, thereby augmenting host resistance against pathogen Listeria monocytogenes infection. Also in tumor implantation study, they caused an increase in CD8⁺ IFN‐γ⁺ T cells to boost the therapeutic efficacy of immune checkpoint inhibitor anti‐PD‐1, thereby inhibiting cancer growth. PD‐1, the programmed cell death protein 1

FIGURE 6

Gut microbiota's local and systemic impacts. Gut microbiota affects locally in listed functions and mucosa immunity. The gut microbiota can also systemically impact the host's many listed physiological functions. Both can possibly influence cancer development and cancer therapeutic efficacy and toxicity [210]

FIGURE 7

Mechanistic roles of microbiota in oncogenesis and tumor suppression. Roles of microbiota are pivotal in regulating oncogenesis or tumor suppression. Microbiota can contribute to oncogenesis or tumor suppression via the listed metabolites or functions. Microbiota dysbiosis may tilt the balance toward oncogenesis