BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

The impact of cancer cachexia on gut microbiota composition and short-chain fatty acid metabolism in a murine model

  • Seung Min Jeong (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Eun-Ju Jin (Department of Precision Medicine, Sungkyunkwan University School of Medicine) ;
  • Shibo Wei (Department of Precision Medicine, Sungkyunkwan University School of Medicine) ;
  • Ju-Hyeon Bae (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Yosep Ji (HEM Inc.) ;
  • Yunju Jo (Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology) ;
  • Jee-Heon Jeong (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Se Jin Im (Department of Immunology, Sungkyunkwan University School of Medicine) ;
  • Dongryeol Ryu (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine)
  • Received : 2023.04.25
  • Accepted : 2023.05.14
  • Published : 2023.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

This study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis. The cachexia group exhibited lower alpha diversity and distinct beta diversity in gut microbiota, compared to the control group. Differential abundance analysis revealed higher Bifidobacterium and Romboutsia, but lower Streptococcus abundance in the cachexia group. Additionally, lower proportions of acetate and butyrate were observed in the cachexia group. The study observed that the impact of cancer cachexia on gut microbiota and their generated metabolites was significant, indicating a host-to-gut microbiota axis.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2023R1A2C3006220 and 2021R1A5A8029876 to D.R.), a "GIST Research Institute (GRI) IIBR" grant funded by the GIST in 2023 (to D.R.), and HEM Inc. We would like to appreciate all lab members of Ryu lab.

References

  1. Jo Y, Yeo MK, Dao T, Kwon J, Yi HS and Ryu D (2022) Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia. Front Oncol 12, 942774
  2. Lee JY, Hong N, Kim HR et al (2018) Effects of serum albumin, calcium levels, cancer stage and performance status on weight loss in parathyroid hormone-related peptide positive or negative patients with cancer. Endocrinol Metab (Seoul) 33, 97-104 https://doi.org/10.3803/EnM.2018.33.1.97
  3. Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12, 489-495 https://doi.org/10.1016/S1470-2045(10)70218-7
  4. Aoyagi T, Terracina KP, Raza A, Matsubara H and Takabe K (2015) Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 7, 17
  5. Ahmed DS, Isnard S, Lin J, Routy B and Routy J-P (2021) GDF15/GFRAL pathway as a metabolic signature for cachexia in patients with cancer. J Cancer 12, 1125
  6. von Haehling S, Anker MS and Anker SD (2016) Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016. J Cachexia Sarcopenia Muscle 7, 507-509 https://doi.org/10.1002/jcsm.12167
  7. Kang BE, Park A, Yang H et al (2022) Machine learning-derived gut microbiome signature predicts fatty liver disease in the presence of insulin resistance. Sci Rep 12, 21842
  8. Lo Sasso G, Ryu D, Mouchiroud L et al (2014) Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer. PLoS One 9, e102495
  9. Lahiri S, Kim H, Garcia-Perez I et al (2019) The gut microbiota influences skeletal muscle mass and function in mice. Sci Transl Med 11, eaan5662
  10. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER and Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027-1031 https://doi.org/10.1038/nature05414
  11. Turnbaugh PJ, Backhed F, Fulton L and Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213-223 https://doi.org/10.1016/j.chom.2008.02.015
  12. Abu-Elheiga L, Oh W, Kordari P and Wakil SJ (2003) Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci U S A 100, 10207-10212 https://doi.org/10.1073/pnas.1733877100
  13. Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761-1772 https://doi.org/10.2337/db06-1491
  14. Grosicki GJ, Fielding RA and Lustgarten MS (2018) Gut microbiota contribute to age-related changes in skeletal muscle size, composition, and function: biological basis for a gut-muscle axis. Calcif Tissue Int 102, 433-442 https://doi.org/10.1007/s00223-017-0345-5
  15. Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R and Calignano A (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 17, 1519
  16. Moon JS, Goeminne LJE, Kim JT et al (2020) Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice. Aging Cell 19, e13195
  17. Han JH, Kim M, Kim HJ et al (2021) Targeting lactate dehydrogenase A with catechin resensitizes SNU620/5FU gastric cancer cells to 5-fluorouracil. Int J Mol Sci 22, 5406