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Abstract

Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signalling, inflammation and adipocyte growth to influence disease severity in obese patients remain largely unclear. Subsequently, while obesity itself is a well-established risk factor for various cancers, the exact mechanisms by which it drives disease progression are not yet definitively known. In this study, we explored the link between obesity-associated microbiome alterations and cancer progression by analysing microbial abundance in tissue samples from obese and cancer patients, and we identified specific microbes correlated with body mass index (BMI) that are associated with key cancer-related pathways. Notably, BMI-associated microbial species such as and were linked with both pro-tumour and anti-tumour progression in cancer patients. Additionally, microbes found to be abundant in cancer and obese tissue, such as , were significantly associated with the upregulation of certain oncogenic signalling pathways. BMI-associated microbes were also correlated with chemokine signalling and TFR2/NFkB-related genes. Both of these have well-established roles in inflammatory activity and inflammasome expression, a critical step in obesity-related cancer progression. Therefore, these microbes were found to be associated with variations in disease prognosis and patient survival. This study provides new insights into how obesity-related microbiome dysbiosis may be associated with cancer development and aims to introduce novel potential avenues for precision medicine approaches in cancer treatment.

Funding
This study was supported by the:
  • University of California, San Diego (Award RG096651)
    • Principal Award Recipient: NotApplicable
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/acmi/10.1099/acmi.0.001055.v4
2025-10-21
2025-11-10

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References

  1. Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM et al. Projected U.S. State-Level prevalence of adult obesity and severe obesity. N Engl J Med 2019; 381:2440–2450 [View Article] [PubMed]
    [Google Scholar]
  2. Sudan SK, Sharma A, Vikramdeo KS, Davis W, Deshmukh SK et al. Obesity and early-onset breast cancer and specific molecular subtype diagnosis in Black and White women. JAMA Netw Open 2024; 7:e2421846 [View Article] [PubMed]
    [Google Scholar]
  3. De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes 2013; 2013:291546 [View Article] [PubMed]
    [Google Scholar]
  4. Ferrante AW. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 2007; 262:408–414 [View Article] [PubMed]
    [Google Scholar]
  5. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112:1796–1808 [View Article] [PubMed]
    [Google Scholar]
  6. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004; 101:15718–15723 [View Article]
    [Google Scholar]
  7. Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat Rev Endocrinol 2015; 11:182–190 [View Article] [PubMed]
    [Google Scholar]
  8. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 2007; 104:979–984 [View Article]
    [Google Scholar]
  9. Million M, Maraninchi M, Henry M, Armougom F, Richet H et al. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes 2012; 36:817–825 [View Article]
    [Google Scholar]
  10. Kasai C, Sugimoto K, Moritani I, Tanaka J, Oya Y et al. Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing. BMC Gastroenterol 2015; 15:100 [View Article] [PubMed]
    [Google Scholar]
  11. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O et al. Human genetics shape the gut microbiome. Cell 2014; 159:789–799 [View Article] [PubMed]
    [Google Scholar]
  12. Hu H-J, Park S-G, Jang HB, Choi M-K, Park K-H et al. Obesity alters the microbial community profile in Korean adolescents. PLoS One 2015; 10:e0134333 [View Article] [PubMed]
    [Google Scholar]
  13. Sanmiguel C, Gupta A, Mayer EA. Gut microbiome and obesity: a plausible explanation for obesity. Curr Obes Rep 2015; 4:250–261 [View Article] [PubMed]
    [Google Scholar]
  14. Yende AS, Sharma D. Obesity, dysbiosis and inflammation: interactions that modulate the efficacy of immunotherapy. Front Immunol 2024; 15:1444589 [View Article] [PubMed]
    [Google Scholar]
  15. Singh S, Sharma P, Sarma D, Kumawat M, Tiwari R et al. Implication of obesity and gut microbiome dysbiosis in the etiology of colorectal cancer. Cancers 2023; 15:1913 [View Article] [PubMed]
    [Google Scholar]
  16. Glassing A, Dowd SE, Galandiuk S, Davis B, Chiodini RJ. Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples. Gut Pathog 2016; 8:24 [View Article] [PubMed]
    [Google Scholar]
  17. Liu Y, Elworth RAL, Jochum MD, Aagaard KM, Treangen TJ. De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee. Nat Commun 2022; 13:6799 [View Article]
    [Google Scholar]
  18. Rampelotto PH, Sereia AFR, de Oliveira LFV, Margis R. Exploring the hospital microbiome by high-resolution 16S rRNA profiling. Int J Mol Sci 2019; 20:3099 [View Article] [PubMed]
    [Google Scholar]
  19. Guo H, Callaway JB, Ting JP-Y. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 2015; 21:677–687 [View Article] [PubMed]
    [Google Scholar]
  20. Qiu Q, Lin Y, Ma Y, Li X, Liang J et al. Exploring the emerging role of the gut microbiota and tumor microenvironment in cancer immunotherapy. Front Immunol 2020; 11:612202 [View Article] [PubMed]
    [Google Scholar]
  21. Sun J, Kato I. Gut microbiota, inflammation and colorectal cancer. Genes & Diseases 2016; 3:130–143 [View Article]
    [Google Scholar]
  22. He Y, Huang J, Li Q, Xia W, Zhang C et al. Gut microbiota and tumor immune escape: a new perspective for improving tumor immunotherapy. Cancers 2022; 14:5317 [View Article] [PubMed]
    [Google Scholar]
  23. Zhao L-Y, Mei J-X, Yu G, Lei L, Zhang W-H et al. Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications. Signal Transduct Target Ther 2023; 8:201 [View Article] [PubMed]
    [Google Scholar]
  24. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, inflammation, and cancer. Annu Rev Pathol Mech Dis 2016; 11:421–449 [View Article]
    [Google Scholar]
  25. Sudan SK, Sharma A, Vikramdeo KS, Davis W, Deshmukh SK et al. Obesity and early-onset breast cancer and specific molecular subtype diagnosis in Black and White women: NIMHD social epigenomics program. JAMA Netw Open 2024; 7:e2421846 [View Article] [PubMed]
    [Google Scholar]
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