Gut Microbiota and Tumor-associated Macrophages: Potential in Tumor Diagnosis and Treatment

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2023 Nov 9

PMID 37943609

Authors

Dongqin Zhou

Yongsheng Li

Affiliations

Soon will be listed here.

Abstract

Avoiding immune destruction and polymorphic microbiomes are two key hallmarks of cancer. The tumor microenvironment (TME) is essential for the development of solid tumors, and the function of tumor-associated macrophages (TAMs) in the TME is closely linked to tumor prognosis. Therefore, research on TAMs could improve the progression and control of certain tumor patients. Additionally, the intestinal flora plays a crucial role in metabolizing substances and maintaining a symbiotic relationship with the host through a complex network of interactions. Recent experimental and clinical studies have suggested a potential link between gut microbiome and TME, particularly in regulating TAMs. Understanding this association could improve the efficacy of tumor immunotherapy. This review highlights the regulatory role of intestinal flora on TAMs, with a focus on gut microbiota and their metabolites. The implications of this association for tumor diagnosis and treatment are also discussed, providing a promising avenue for future clinical treatment strategies.

Citing Articles

Probiotic-Derived Metabolites from OC01 Reprogram Tumor-Associated Macrophages to an Inflammatory Anti-Tumoral Phenotype: Impact on Colorectal Cancer Cell Proliferation and Migration.

Garavaglia B, Vallino L, Ferraresi A, Amoruso A, Pane M, Isidoro C Biomedicines. 2025; 13(2).

PMID: 40002754 PMC: 11853712. DOI: 10.3390/biomedicines13020339.

From silent partners to potential therapeutic targets: macrophages in colorectal cancer.

Khizar H, Ali K, Wang J Cancer Immunol Immunother. 2025; 74(4):121.

PMID: 39998578 PMC: 11861851. DOI: 10.1007/s00262-025-03965-w.

Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota.

Yang M, Guo J, Li J, Wang S, Sun Y, Liu Y J Nanobiotechnology. 2025; 23(1):92.

PMID: 39920791 PMC: 11804104. DOI: 10.1186/s12951-025-03139-x.

Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date.

Giammona A, Galuzzi B, Imperia E, Gervasoni C, Remedia S, Restaneo L Int J Mol Sci. 2025; 26(1.

PMID: 39796266 PMC: 11720538. DOI: 10.3390/ijms26010413.

Advances in Molecular Mechanisms and Therapeutic Strategies in Colorectal Cancer: A New Era of Precision Medicine.

Delle Cave D Int J Mol Sci. 2025; 26(1.

PMID: 39796202 PMC: 11719900. DOI: 10.3390/ijms26010346.

References

Li X, Qi M, He K, Liu H, Yan W, Zhao L . Neospora caninum inhibits tumor development by activating the immune response and destroying tumor cells in a B16F10 melanoma model. Parasit Vectors. 2022; 15(1):332. PMC: 9503190. DOI: 10.1186/s13071-022-05456-8. View

Chu C, Wang S, Li C, Chen S, Hu C, Chung Y . Neurons and astroglia govern microglial endotoxin tolerance through macrophage colony-stimulating factor receptor-mediated ERK1/2 signals. Brain Behav Immun. 2016; 55:260-272. PMC: 4899166. DOI: 10.1016/j.bbi.2016.04.015. View

Rohm T, Fuchs R, Muller R, Keller L, Baumann Z, Bosch A . Obesity in Humans Is Characterized by Gut Inflammation as Shown by Pro-Inflammatory Intestinal Macrophage Accumulation. Front Immunol. 2021; 12:668654. PMC: 8158297. DOI: 10.3389/fimmu.2021.668654. View

Liu Y, Xu J, Ren X, Zhang Y, Ke Z, Zhou J . Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment. Gut Microbes. 2022; 14(1):2107387. PMC: 9450905. DOI: 10.1080/19490976.2022.2107387. View

Han G, Kim S, Ko W, Lee D, Han I, Sheen S . Transplantation of tauroursodeoxycholic acid-inducing M2-phenotype macrophages promotes an anti-neuroinflammatory effect and functional recovery after spinal cord injury in rats. Cell Prolif. 2021; 54(6):e13050. PMC: 8168422. DOI: 10.1111/cpr.13050. View

Fan Y, Su Q, Chen J, Wang Y, He S . Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice. Front Oncol. 2022; 12:836953. PMC: 8957261. DOI: 10.3389/fonc.2022.836953. View

Zegarra Ruiz D, Kim D, Norwood K, Saldana-Morales F, Kim M, Ng C . Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer. Gut Microbes. 2022; 14(1):2119054. PMC: 9450902. DOI: 10.1080/19490976.2022.2119054. View

Shinde R, McGaha T . The Aryl Hydrocarbon Receptor: Connecting Immunity to the Microenvironment. Trends Immunol. 2018; 39(12):1005-1020. PMC: 7182078. DOI: 10.1016/j.it.2018.10.010. View

Baruch E, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L . Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2020; 371(6529):602-609. DOI: 10.1126/science.abb5920. View

10.

Kushwaha V, Rai P, Varshney S, Gupta S, Khandelwal N, Kumar D . Sodium butyrate reduces endoplasmic reticulum stress by modulating CHOP and empowers favorable anti-inflammatory adipose tissue immune-metabolism in HFD fed mice model of obesity. Food Chem (Oxf). 2022; 4:100079. PMC: 8991629. DOI: 10.1016/j.fochms.2022.100079. View

11.

Jeong J, Kim K, Hwang Y, Han M, Kim D . Anti-inflammaging effects of Lactobacillus brevis OW38 in aged mice. Benef Microbes. 2016; 7(5):707-718. DOI: 10.3920/BM2016.0016. View

12.

DAlessandro G, Lauro C, Quaglio D, Ghirga F, Botta B, Trettel F . Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma. Cancers (Basel). 2021; 13(11). PMC: 8200200. DOI: 10.3390/cancers13112810. View

13.

Zmora N, Suez J, Elinav E . You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2018; 16(1):35-56. DOI: 10.1038/s41575-018-0061-2. View

14.

Chang P, Hao L, Offermanns S, Medzhitov R . The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014; 111(6):2247-52. PMC: 3926023. DOI: 10.1073/pnas.1322269111. View

15.

Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y . Microbial metabolite butyrate facilitates M2 macrophage polarization and function. Sci Rep. 2016; 6:24838. PMC: 4837405. DOI: 10.1038/srep24838. View

16.

Shapira M . Gut Microbiotas and Host Evolution: Scaling Up Symbiosis. Trends Ecol Evol. 2016; 31(7):539-549. DOI: 10.1016/j.tree.2016.03.006. View

17.

Hu Y, Li J, Ni F, Yang Z, Gui X, Bao Z . CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies. Nat Commun. 2022; 13(1):5313. PMC: 9461447. DOI: 10.1038/s41467-022-32960-3. View

18.

Chao X, Lei Z, Hongqin L, Ziwei W, Dechuan L, Weidong D . Faeces from malnourished colorectal cancer patients accelerate cancer progression. Clin Nutr. 2022; 41(3):632-644. DOI: 10.1016/j.clnu.2022.01.001. View

19.

Rooks M, Garrett W . Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016; 16(6):341-52. PMC: 5541232. DOI: 10.1038/nri.2016.42. View

20.

Shu Y, Cheng P . Targeting tumor-associated macrophages for cancer immunotherapy. Biochim Biophys Acta Rev Cancer. 2020; 1874(2):188434. DOI: 10.1016/j.bbcan.2020.188434. View