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Review
. 2024 Mar 17;14(6):2304-2328.
doi: 10.7150/thno.91700. eCollection 2024.

Role of the gut microbiota in tumorigenesis and treatment

Qingya Liu  1 , Yun Yang  1 , Meng Pan  1 , Fan Yang  2 , Yan Yu  1 , Zhiyong Qian  1
Affiliations
Review

Role of the gut microbiota in tumorigenesis and treatment

Qingya Liu et al. Theranostics. .

Abstract

The gut microbiota is a crucial component of the intricate microecosystem within the human body that engages in interactions with the host and influences various physiological processes and pathological conditions. In recent years, the association between dysbiosis of the gut microbiota and tumorigenesis has garnered increasing attention, as it is recognized as a hallmark of cancer within the scientific community. However, only a few microorganisms have been identified as potential drivers of tumorigenesis, and enhancing the molecular understanding of this process has substantial scientific importance and clinical relevance for cancer treatment. In this review, we delineate the impact of the gut microbiota on tumorigenesis and treatment in multiple types of cancer while also analyzing the associated molecular mechanisms. Moreover, we discuss the utility of gut microbiota data in cancer diagnosis and patient stratification. We further outline current research on harnessing microorganisms for cancer treatment while also analyzing the prospects and challenges associated with this approach.

Keywords: cancer; dysbiosis; fecal microbiota transplantation (FMT); gut microbiota; probiotics.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Cancer types associated with dysbiosis of the gut microbiota. This figure was created using Figdraw.
Figure 2
Figure 2
Estrogen metabolism is mediated by gut microbial β-glucuronidase (gmGUS: gut microbial β-glucuronidase). The hepatic metabolism of estrogen is facilitated by a cascade of enzymes. The conjugation of parent estrogens and their phase I metabolites with glucuronic acid can be catalyzed by uridine 5′-diphospho-glucuronosyltransferase (UGT). Estrogen glucuronides are biologically inactive; upon bile excretion, they undergo gastrointestinal transit, during which gmGUS enzymatically hydrolyzes the conjugates to release active estrogens. The reactivated estrogens enter the hepatic circulation and are subsequently reabsorbed into the body. CYP, cytochrome P-450 enzyme. Adapted with permission from , Copyright 2021, Sui, Wu and Chen.
Figure 3
Figure 3
Gut microbiota dysbiosis contributes to the development of CRC through a diverse range of molecular mechanisms. (A) pks+ E. coli and C. jejuni produce genotoxins, which induce DNA damage and increase the frequency of gene mutations, thus contributing to CRC. (B) F. nucleatum leads to the expansion of MDSCs, CD11b+ cells, M2 TAMs, and TANs. These cells play a crucial role in suppressing antitumor immunity. (C) B. fragilis triggers a procarcinogenic, multistep inflammatory cascade involving the IL-17R, NF-kB, and STAT3 signaling pathways in colonic epithelial cells. (D) Red/processed meat can potentially modify the structure and function of the microbiota, leading to increased production of H2S and secondary bile acids by microorganisms. These alterations can result in damage to gut barrier function and DNA, thereby elevating the risk of CRC. MDSCs: myeloid-derived suppressor cells; TANs: tumor-associated neutrophils; M2 TAMs: M2-like tumor-associated macrophages; H2S: hydrogen sulfide. This figure was created using Figdraw.
Figure 4
Figure 4
Contribution of the gut microbiota to HCC and the underlying mechanisms involved Dysbiosis of the gut microbiota and impairment of the gut barrier result in the translocation of LPS from the gut lumen to the bloodstream, leading to increased hepatic exposure to LPS. This promotes hepatic inflammation, fibrosis, proliferation and the activation of antiapoptotic signals. This figure was created using Figdraw.
Figure 5
Figure 5
This article provides an overview of gut microbiota-cancer therapy interactions. The gut microbiota induces adaptive immunity, and A. muciniphila reverses the nonresponse to PD-1/PD-L inhibitors. The metabolite 3-IAA, produced by the gut microbiota, enhances the efficacy of chemotherapy. Supplementation with Lactobacillus plantarum NCU116 can reduce the damage caused by CTX to the gut mucosa. However, β-glucuronidases produced by the gut microbiota can convert SN-38G into SN-38, which is toxic to the gut. Radiation therapy can result in a reduction in the diversity of the gut microbiota and an increase in the abundance of pathogenic bacteria, whereas supplementation with probiotics and prebiotics exerts a protective effect against radiation-induced damage. The use of FMT is indicated for the treatment of diarrhea resulting from TKI therapy. The administration of preoperative antibiotics may result in a reduction in gut microbial diversity and the proliferation of pathogenic bacteria, which can compromise gut barrier function. Conversely, probiotic supplementation has been shown to enhance gut barrier function. This figure was created using Figdraw.
Figure 6
Figure 6
Utilization of gut microbiota data in cancer diagnosis and patient stratification. This figure was created using Figdraw.
Figure 7
Figure 7
Strategies to modify the gut microbiota for cancer treatment The modulation of the gut microbiota through FMT, probiotics, and dietary regulation primarily contributes to the enrichment of probiotics. The current practice primarily involves the use of antibiotics for eradicating pathogenic bacteria, which may have detrimental effects on treatment outcomes. However, the application of nanomedicines offers opportunities for targeted elimination of pathogenic bacteria. This figure was created using Figdraw.
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