1. Shay, J. E. S. \& Yilmaz, ÖH. Dietary and metabolic effects on intestinal stem cells in health and disease. Nat. Rev. Gastroenterol. Hepatol. 22, 23–38 (2025).

Article 
PubMed 
Google Scholar
2. Beyaz, S. et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531, 53–58 (2016).

Article 
ADS 
CAS 
PubMed 
PubMed Central 
Google Scholar
3. Lien, E. C. \& Heiden, M. G. V. A framework for examining how diet impacts tumour metabolism. Nat. Rev. Cancer 19, 651–661 (2019).

Article 
CAS 
PubMed 
Google Scholar
4. Jagelman, D. G., Decosse, J. J., Bussey, H. J. R. \& The Leeds Castle Polyposis Group. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 331, 1149–1151 (1988).

Article 
Google Scholar
5. Willett, W. C., Stampfer, M. J., Colditz, G. A., Rosner, B. A. \& Speizer, F. E. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N. Engl. J. Med. 323, 1664–1672 (1990).

Article 
CAS 
PubMed 
Google Scholar
6. Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333–339 (2017).

Article 
ADS 
CAS 
PubMed 
PubMed Central 
Google Scholar
7. Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).

Article 
ADS 
CAS 
PubMed 
Google Scholar
8. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).

Article 
ADS 
CAS 
PubMed 
Google Scholar
9. Mehta, R. S. et al. Dietary patterns and risk of colorectal cancer: analysis by tumor location and molecular subtypes. Gastroenterology 152, 1944–1953 (2017).

Article 
CAS 
PubMed 
PubMed Central 
Google Scholar
10. Zaborowski, A. M. et al. Characteristics of early-onset vs late-onset colorectal cancer. JAMA Surg. 156, 865 (2021).

[Article](https://doi.org/10.1001%2Fjamasurg.2021.2380) 
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=34190968) 
[Google Scholar](http://scholar.google.com/scholar_lookup?&title=Characteristics%20of%20early-onset%20vs%20late-onset%20colorectal%20cancer&journal=JAMA%20Surg.&doi=10.1001%2Fjamasurg.2021.2380&volume=156&publication_year=2021&author=Zaborowski%2CAM)
  1. GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 377, 13–27 (2017).

    Article 
    Google Scholar
    12. Ng, M. et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384, 766–781 (2014).

    Article 
    PubMed 
    PubMed Central 
    Google Scholar
    13. Beyaz, S. et al. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell 28, 1922–1935 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    14. Mana, M. D. et al. High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity. Cell Rep. 35, 109212 (2021).

    Article 
    CAS 
    PubMed 
    Google Scholar
    15. DeClercq, V., McMurray, D. N. \& Chapkin, R. S. Obesity promotes colonic stem cell expansion during cancer initiation. Cancer Lett. 369, 336–343 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    16. Wasan, H. S., Novelli, M., Bee, J. \& Bodmer, W. F. Dietary fat influences on polyp phenotype in multiple intestinal neoplasia mice. Proc. Natl Acad. Sci. USA 94, 3308–3313 (1997).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    17. Newmark, H. L. et al. A Western-style diet induces benign and malignant neoplasms in the colon of normal C57BL/6 mice. Carcinogenesis 22, 1871–1875 (2001).

    Article 
    CAS 
    PubMed 
    Google Scholar
    18. Mihaylova, M. M. et al. Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem Cell 22, 769–778 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    19. Cheng, C.-W. et al. Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet. Cell 178, 1115–1131 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    20. Pak, H. H. et al. Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. Nat. Metab. 3, 1327–1341 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    21. Bruens, L. et al. Calorie restriction increases the number of competing stem cells and decreases mutation retention in the intestine. Cell Rep. 32, 107937 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    22. Mai, V. et al. Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in Apc(min) mice through different mechanisms. Cancer Res. 63, 1752–1755 (2003).

    CAS 
    PubMed 
    Google Scholar
    23. Mitchell, S. J. et al. Daily fasting improves health and survival in male mice independent of diet composition and calories. Cell Metab. 29, 221–228 (2019).

    Article 
    CAS 
    PubMed 
    Google Scholar
    24. Yilmaz, ÖH. et al. MTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486, 490–495 (2012).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    25. Imada, S. et al. Short-term post-fast refeeding enhances intestinal stemness via polyamines. Nature 633, 895–904 (2024).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    26. Roberts, M. N. et al. Short article. A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab. 26, 539–546 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    27. Newman, J. C. \& Verdin, E. β-Hydroxybutyrate: a signaling metabolite. Ann. Rev. Nutrit. 37, 51–76 (2017).

    Article 
    CAS 
    Google Scholar
    28. Puchalska, P. \& Crawford, P. A. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab. 25, 262–284 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    29. Dmitrieva-Posocco, O. et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature 605, 160–165 (2022).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    30. Nugent, K. P., Spigelman, A. D. \& Phillips, R. K. S. Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis. Dis. Colon Rectum 36, 1059–1062 (1993).

    Article 
    CAS 
    PubMed 
    Google Scholar
    31. Groves, C. J., Saunders, B. P., Spigelman, A. D. \& Phillips, R. K. S. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut 50, 636 (2002).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    32. Weiss, J. M. et al. NCCN Guidelines® insights: genetic/familial high-risk assessment: colorectal, version 1.2021. J. Natl Compr. Cancer Netw. 19, 1122–1132 (2021).

    Google Scholar
    33. Karstensen, J. G. et al. Cancer in patients with familial adenomatous polyposis: a nationwide Danish cohort study with matched controls. Gastroenterology 165, 573–581 (2023).

    Article 
    PubMed 
    Google Scholar
    34. Taylor, S. R., Falcone, J. N., Cantley, L. C. \& Goncalves, M. D. Developing dietary interventions as therapy for cancer. Nat. Rev. Cancer 22, 452–466 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    35. Goto, N. et al. Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury. Cell Stem Cell 29, 1246–1261 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    36. Gao, R. et al. Integrated analysis of colorectal cancer reveals cross-cohort gut microbial signatures and associated serum metabolites. Gastroenterology 163, 1024–1037 (2022).

    Article 
    CAS 
    PubMed 
    Google Scholar
    37. Aliluev, A. et al. Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice. Nat. Metab. 3, 1202–1216 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    38. Tsenkova, M. et al. Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate. Nat. Commun. 16, 1792 (2025).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    39. Müller-Dott, S. et al. Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities. Nucleic Acids Res. 51, 10934–10949 (2023).

    Article 
    PubMed 
    PubMed Central 
    Google Scholar
    40. Shou, J. et al. Minimum dietary fat threshold for effective ketogenesis and obesity control in mice. Nutrients 17, 3203 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    41. Yeh, C. et al. Ketogenesis is dispensable for the metabolic adaptations to caloric restriction. Aging Cell 25, e70318 (2026).

    Article 
    CAS 
    PubMed 
    Google Scholar
    42. Hopkins, B. D. et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560, 499–503 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    43. Xia, S. et al. Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth. Cell Metab. 25, 358–373 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    44. Lien, E. C. et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature 599, 302–307 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    45. Vieira, R. F. et al. Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth. Cancer Metab. 13, 39 (2025).

    Article 
    PubMed 
    PubMed Central 
    Google Scholar
    46. Colnot, S. et al. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab. Investig. 84, 1619–1630 (2004).

    Article 
    CAS 
    PubMed 
    Google Scholar
    47. Marjou, F. E. et al. Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39, 186–193 (2004).

    Article 
    PubMed 
    Google Scholar
    48. Horton, J. L. et al. The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight 4, e124079 (2019).

    Article 
    PubMed 
    PubMed Central 
    Google Scholar
    49. Cotter, D. G., Schugar, R. C., Wentz, A. E., D’Avignon, D. A. \& Crawford, P. A. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation. Am. J. Physiol. Endocrinol. Metabol. 304, E363–E374 (2013).

    Article 
    CAS 
    Google Scholar
    50. Schoors, S. et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520, 192–197 (2015).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    51. Hsieh, W.-Y., Williams, K. J., Su, B. \& Bensinger, S. J. Profiling of mouse macrophage lipidome using direct infusion shotgun mass spectrometry. STAR Protoc. 2, 100235 (2021).

    Article 
    CAS 
    PubMed 
    Google Scholar
    52. Su, B. et al. A DMS shotgun lipidomics workflow application to facilitate high-throughput, comprehensive lipidomics. J. Am. Soc. Mass. Spectrom. 32, 2655–2663 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Google Scholar
    53. Korotkevich, G. et al. Fast gene set enrichment analysis. Preprint at bioRxiv https://doi.org/10.1101/060012 (2021).