#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine


Autoři: Jakob von Frieling aff001;  Muhammed Naeem Faisal aff001;  Femke Sporn aff001;  Roxana Pfefferkorn aff001;  Stella Solveig Nolte aff001;  Felix Sommer aff002;  Philip Rosenstiel aff002;  Thomas Roeder aff001
Působiště autorů: Zoological Institute, Department of Molecular Physiology, Kiel University, Kiel, Germany aff001;  IKMB, UKSH, Kiel University, Kiel, Germany aff002;  German Center for Lung Research, Airway Research Center North, Kiel, Germany aff003
Vyšlo v časopise: A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008789
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008789

Souhrn

Over-consumption of high-fat diets (HFDs) is associated with several pathologies. Although the intestine is the organ that comes into direct contact with all diet components, the impact of HFD has mostly been studied in organs that are linked to obesity and obesity related disorders. We used Drosophila as a simple model to disentangle the effects of a HFD on the intestinal structure and physiology from the plethora of other effects caused by this nutritional intervention. Here, we show that a HFD, composed of triglycerides with saturated fatty acids, triggers activation of intestinal stem cells in the Drosophila midgut. This stem cell activation was transient and dependent on the presence of an intestinal microbiota, as it was completely absent in germ free animals. Moreover, major components of the signal transduction pathway have been elucidated. Here, JNK (basket) in enterocytes was necessary to trigger synthesis of the cytokine upd3 in these cells. This ligand in turn activated the JAK/STAT pathway in intestinal stem cells. Chronic subjection to a HFD markedly altered both the microbiota composition and the bacterial load. Although HFD-induced stem cell activity was transient, long-lasting changes to the cellular composition, including a substantial increase in the number of enteroendocrine cells, were observed. Taken together, a HFD enhances stem cell activity in the Drosophila gut and this effect is completely reliant on the indigenous microbiota and also dependent on JNK signaling within intestinal enterocytes.

Klíčová slova:

Bacteria – c-Jun N-terminal kinase signaling cascade – Diet – Drosophila melanogaster – Fatty acids – Gastrointestinal tract – Microbiome – Quantitative analysis


Zdroje

1. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007;132(6):2087–102. doi: 10.1053/j.gastro.2007.03.052 17498505.

2. Alonso S, Yilmaz OH. Nutritional Regulation of Intestinal Stem Cells. Annu Rev Nutr. 2018;38:273–301. Epub 2018/05/26. doi: 10.1146/annurev-nutr-082117-051644 29799767.

3. Haller S, Jasper H. You Are What You Eat: Linking High-Fat Diet to Stem Cell Dysfunction and Tumorigenesis. Cell Stem Cell. 2016;18(5):564–6. doi: 10.1016/j.stem.2016.04.010 27152439.

4. Yilmaz OH, Katajisto P, Lamming DW, Gultekin Y, Bauer-Rowe KE, Sengupta S, et al. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature. 2012;486(7404):490–5. doi: 10.1038/nature11163 22722868.

5. O'Brien LE, Soliman SS, Li X, Bilder D. Altered modes of stem cell division drive adaptive intestinal growth. Cell. 2011;147(3):603–14. doi: 10.1016/j.cell.2011.08.048 22036568.

6. Zeituni EM, Wilson MH, Zheng X, Iglesias PA, Sepanski MA, Siddiqi MA, et al. Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses. J Biol Chem. 2016;291(45):23804–16. doi: 10.1074/jbc.M116.749358 27655916.

7. Obniski R, Sieber M, Spradling AC. Dietary Lipids Modulate Notch Signaling and Influence Adult Intestinal Development and Metabolism in Drosophila. Dev Cell. 2018;47(1):98–111.e5. Epub 2018/09/18. doi: 10.1016/j.devcel.2018.08.013 30220569.

8. Mao J, Hu X, Xiao Y, Yang C, Ding Y, Hou N, et al. Overnutrition stimulates intestinal epithelium proliferation through beta-catenin signaling in obese mice. Diabetes. 2013;62(11):3736–46. doi: 10.2337/db13-0035 23884889.

9. Beyaz S, Yilmaz OH. Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-delta Pathway. Clin Cancer Res. 2016;22(23):5636–41. doi: 10.1158/1078-0432.CCR-16-0775 27702819.

10. Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016;531(7592):53–8. Epub 2016/03/05. doi: 10.1038/nature17173 26935695.

11. Nystrom M, Mutanen M. Diet and epigenetics in colon cancer. World J Gastroenterol. 2009;15(3):257–63. doi: 10.3748/wjg.15.257 19140224.

12. Reddy BS. Types and amount of dietary fat and colon cancer risk: Prevention by omega-3 fatty acid-rich diets. Environ Health Prev Med. 2002;7(3):95–102. doi: 10.1265/ehpm.2002.95 21432290.

13. Newmark HL, Yang K, Lipkin M, Kopelovich L, Liu Y, Fan K, et al. A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis. 2001;22(11):1871–5. doi: 10.1093/carcin/22.11.1871 11698351.

14. Ning Y, Wang L, Giovannucci EL. A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev. 2010;11(1):19–30. doi: 10.1111/j.1467-789X.2009.00613.x 19538439.

15. Karunanithi S, Levi L, DeVecchio J, Karagkounis G, Reizes O, Lathia JD, et al. RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis. Stem Cell Reports. 2017;9(2):438–50. doi: 10.1016/j.stemcr.2017.06.002 28689994.

16. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470–81. doi: 10.2337/db07-1403 18305141.

17. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50(11):2374–83. doi: 10.1007/s00125-007-0791-0 17823788.

18. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137(5):1716–24.e1-2. doi: 10.1053/j.gastro.2009.08.042 19706296.

19. Kim KA, Gu W, Lee IA, Joh EH, Kim DH. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One. 2012;7(10):e47713. doi: 10.1371/journal.pone.0047713 23091640.

20. de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol. 2010;299(2):G440–8. doi: 10.1152/ajpgi.00098.2010 20508158.

21. Daniel H, Gholami AM, Berry D, Desmarchelier C, Hahne H, Loh G, et al. High-fat diet alters gut microbiota physiology in mice. ISME J. 2014;8(2):295–308. doi: 10.1038/ismej.2013.155 24030595.

22. Fink C, Staubach F, Kuenzel S, Baines JF, Roeder T. Noninvasive analysis of microbiome dynamics in the fruit fly Drosophila melanogaster. Appl Environ Microbiol. 2013;79(22):6984–8. Epub 2013/09/10. doi: 10.1128/AEM.01903-13 24014528.

23. Li X, Watanabe K, Kimura I. Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for Diabetes Mellitus and Related Metabolic Diseases. Front Immunol. 2017;8:1882. doi: 10.3389/fimmu.2017.01882 29326727.

24. Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut. 2014;63(9):1513–21. doi: 10.1136/gutjnl-2014-306928 24833634.

25. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–23. doi: 10.1073/pnas.0407076101 15505215.

26. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31. doi: 10.1038/nature05414 17183312.

27. Guo L, Karpac J, Tran SL, Jasper H. PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell. 2014;156(1–2):109–22. Epub 2014/01/21. doi: 10.1016/j.cell.2013.12.018 24439372.

28. Buchon N, Broderick NA, Chakrabarti S, Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 2009;23(19):2333–44. Epub 2009/10/03. doi: 10.1101/gad.1827009 19797770.

29. Buchon N, Broderick NA, Poidevin M, Pradervand S, Lemaitre B. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe. 2009;5(2):200–11. doi: 10.1016/j.chom.2009.01.003 19218090.

30. Antonello ZA, Reiff T, Ballesta-Illan E, Dominguez M. Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch. EMBO J. 2015;34(15):2025–41. Epub 2015/06/17. doi: 10.15252/embj.201591517 26077448.

31. Martin JL, Sanders EN, Moreno-Roman P, Jaramillo Koyama LA, Balachandra S, Du X, et al. Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of division, differentiation and loss. Elife. 2018;7. Epub 2018/11/15. doi: 10.7554/eLife.36248 30427308.

32. Chatterjee N, Bohmann D. A versatile PhiC31 based reporter system for measuring AP-1 and Nrf2 signaling in Drosophila and in tissue culture. PLoS One. 2012;7(4):e34063. doi: 10.1371/journal.pone.0034063 22509270.

33. Chakrabarti S, Dudzic JP, Li X, Collas EJ, Boquete JP, Lemaitre B. Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila. PLoS Genet. 2016;12(5):e1006089. doi: 10.1371/journal.pgen.1006089 27231872.

34. Bach EA, Ekas LA, Ayala-Camargo A, Flaherty MS, Lee H, Perrimon N, et al. GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns. 2007;7(3):323–31. Epub 2006/09/30. doi: 10.1016/j.modgep.2006.08.003 17008134.

35. Singh A, Balint JA, Edmonds RH, Rodgers JB. Adaptive changes of the rat small intestine in response to a high fat diet. Biochim Biophys Acta. 1972;260(4):708–15. doi: 10.1016/0005-2760(72)90019-7 5028118.

36. Sagher FA, Dodge JA, Johnston CF, Shaw C, Buchanan KD, Carr KE. Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat. Br J Nutr. 1991;65(1):21–8. doi: 10.1079/bjn19910062 1705145.

37. Balint JA, Fried MB, Imai C. Ileal uptake of oleic acid: evidence for adaptive response to high fat feeding. Am J Clin Nutr. 1980;33(11):2276–80. doi: 10.1093/ajcn/33.11.2276 7435405.

38. Murphy EA, Velazquez KT, Herbert KM. Influence of high-fat diet on gut microbiota: a driving force for chronic disease risk. Curr Opin Clin Nutr Metab Care. 2015;18(5):515–20. Epub 2015/07/15. doi: 10.1097/MCO.0000000000000209 26154278.

39. Anitha M, Reichardt F, Tabatabavakili S, Nezami BG, Chassaing B, Mwangi S, et al. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice. Cell Mol Gastroenterol Hepatol. 2016;2(3):328–39. doi: 10.1016/j.jcmgh.2015.12.008 27446985.

40. vd Baan-Slootweg OH, Liem O, Bekkali N, van Aalderen WM, Rijcken TH, Di Lorenzo C, et al. Constipation and colonic transit times in children with morbid obesity. J Pediatr Gastroenterol Nutr. 2011;52(4):442–5. doi: 10.1097/MPG.0b013e3181ef8e3c 21240026.

41. Taba Taba Vakili S, Nezami BG, Shetty A, Chetty VK, Srinivasan S. Association of high dietary saturated fat intake and uncontrolled diabetes with constipation: evidence from the National Health and Nutrition Examination Survey. Neurogastroenterol Motil. 2015;27(10):1389–97. doi: 10.1111/nmo.12630 26176421.

42. He L, Si G, Huang J, Samuel ADT, Perrimon N. Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel. Nature. 2018;555(7694):103–6. doi: 10.1038/nature25744 29414942.

43. Wu H, Wang MC, Bohmann D. JNK protects Drosophila from oxidative stress by trancriptionally activating autophagy. Mech Dev. 2009;126(8–9):624–37. doi: 10.1016/j.mod.2009.06.1082 19540338.

44. Stronach BE, Perrimon N. Stress signaling in Drosophila. Oncogene. 1999;18(45):6172–82. doi: 10.1038/sj.onc.1203125 10557109.

45. Zhou F, Rasmussen A, Lee S, Agaisse H. The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment. Dev Biol. 2013;373(2):383–93. doi: 10.1016/j.ydbio.2012.10.023 23110761.

46. Gervais L, Bardin AJ. Tissue homeostasis and aging: new insight from the fly intestine. Curr Opin Cell Biol. 2017;48:97–105. doi: 10.1016/j.ceb.2017.06.005 28719867.

47. Little TJ, Horowitz M, Feinle-Bisset C. Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: implications for the pathophysiology of obesity. Am J Clin Nutr. 2007;86(3):531–41. doi: 10.1093/ajcn/86.3.531 17823414.

48. Richards P, Pais R, Habib AM, Brighton CA, Yeo GS, Reimann F, et al. High fat diet impairs the function of glucagon-like peptide-1 producing L-cells. Peptides. 2016;77:21–7. doi: 10.1016/j.peptides.2015.06.006 26145551.

49. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444(7121):854–9. doi: 10.1038/nature05484 17167473.

50. Cheung GW, Kokorovic A, Lam CK, Chari M, Lam TK. Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metab. 2009;10(2):99–109. doi: 10.1016/j.cmet.2009.07.005 19656488.

51. Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, et al. N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake. Cell. 2008;135(5):813–24. doi: 10.1016/j.cell.2008.10.043 19041747.

52. El-Salhy M, Mazzawi T, Gundersen D, Hatlebakk JG, Hausken T. Changes in the symptom pattern and the densities of large-intestinal endocrine cells following Campylobacter infection in irritable bowel syndrome: a case report. BMC Res Notes. 2013;6:391. doi: 10.1186/1756-0500-6-391 24073715.

53. Pilichiewicz AN, Little TJ, Brennan IM, Meyer JH, Wishart JM, Otto B, et al. Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men. Am J Physiol Regul Integr Comp Physiol. 2006;290(3):R668–77. doi: 10.1152/ajpregu.00606.2005 16210415.

54. Feinle-Bisset C, Patterson M, Ghatei MA, Bloom SR, Horowitz M. Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid. Am J Physiol Endocrinol Metab. 2005;289(6):E948–53. doi: 10.1152/ajpendo.00220.2005 15998659.

55. Spannagel AW, Nakano I, Tawil T, Chey WY, Liddle RA, Green GM. Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats. Am J Physiol. 1996;270(1 Pt 1):G128–35. doi: 10.1152/ajpgi.1996.270.1.G128 8772510.

56. van Citters GW, Kabir M, Kim SP, Mittelman SD, Dea MK, Brubaker PL, et al. Elevated glucagon-like peptide-1-(7–36)-amide, but not glucose, associated with hyperinsulinemic compensation for fat feeding. J Clin Endocrinol Metab. 2002;87(11):5191–8. doi: 10.1210/jc.2002-020002 12414891.

57. Worthington JJ. The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease. Biochem Soc Trans. 2015;43(4):727–33. doi: 10.1042/BST20150090 26551720.

58. Scopelliti A, Cordero JB, Diao F, Strathdee K, White BH, Sansom OJ, et al. Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut. Curr Biol. 2014;24(11):1199–211. Epub 2014/05/13. doi: 10.1016/j.cub.2014.04.007 24814146.

59. Leitao-Goncalves R, Carvalho-Santos Z, Francisco AP, Fioreze GT, Anjos M, Baltazar C, et al. Commensal bacteria and essential amino acids control food choice behavior and reproduction. PLoS Biol. 2017;15(4):e2000862. Epub 2017/04/26. doi: 10.1371/journal.pbio.2000862 28441450.

60. Hoffmann J, Romey R, Fink C, Yong L, Roeder T. Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila. Aging (Albany NY). 2013;5(4):315–27. Epub 2013/06/15. doi: 10.18632/aging.100553 23765091.

61. Markstein M, Dettorre S, Cho J, Neumuller RA, Craig-Muller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc Natl Acad Sci U S A. 2014;111(12):4530–5. Epub 2014/03/13. doi: 10.1073/pnas.1401160111 24616500.

62. Warmbold C, Uliczka K, Rus F, Suck R, Petersen A, Silverman N, et al. Dermatophagoides pteronyssinus major allergen 1 activates the innate immune response of the fruit fly Drosophila melanogaster. J Immunol. 2013;190(1):366–71. Epub 2012/12/04. doi: 10.4049/jimmunol.1201347 23203927.

63. Sommer F, Adam N, Johansson MEV, Xia L, Hansson GC, Bäckhed F. Altered Mucus Glycosylation in Core 1 O-Glycan-Deficient Mice Affects Microbiota Composition and Intestinal Architecture. PLoS One. 2014;9(1):e85254.

64. Sommer F, Ståhlman M, Ilkayeva O, Arnemo Jon M, Kindberg J, Josefsson J, et al. The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos. Cell Reports. 2016;14(7):1655–61. doi: 10.1016/j.celrep.2016.01.026 26854221

65. Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6(8):1621–4. doi: 10.1038/ismej.2012.8 22402401.

66. http://www.wernerlab.org/software/macqiime.

67. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome biology. 2011;12(6):R60. doi: 10.1186/gb-2011-12-6-r60 21702898.


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 5
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#