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Modulation of intestinal stem cell homeostasis by nutrients: a novel therapeutic option for intestinal diseases

Published online by Cambridge University Press:  08 June 2021

Dan Wang ,
Pei Li ,
Jack Odle ,
Xi Lin ,
Jiangchao Zhao ,
Kan Xiao  and
Yulan Liu
Dan Wang
Affiliation:
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People’s Republic of China
Pei Li
Affiliation:
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People’s Republic of China
Jack Odle
Affiliation:
Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA
Xi Lin
Affiliation:
Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA
Jiangchao Zhao
Affiliation:
Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USA
Kan Xiao
Affiliation:
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People’s Republic of China
Yulan Liu*
Affiliation:
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People’s Republic of China
*
*Corresponding author: Yulan Liu, email: yulanflower@126.com
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Abstract

Intestinal stem cells, which are capable of both self-renewal and differentiation to mature cell types, are responsible for maintaining intestinal epithelial homeostasis. Recent evidence indicates that these processes are mediated, in part, through nutritional status in response to diet. Diverse dietary patterns including caloric restriction, fasting, high-fat diets, ketogenic diets and high-carbohydrate diets as well as other nutrients control intestinal stem cell self-renewal and differentiation through nutrient-sensing pathways such as mammalian target of rapamycin and AMP-activated kinase. Herein, we summarise the current understanding of how intestinal stem cells contribute to intestinal epithelial homeostasis and diseases. We also discuss the effects of diet and nutrient-sensing pathways on intestinal stem cell self-renewal and differentiation, as well as their potential application in the prevention and treatment of intestinal diseases.

Keywords

Intestinal stem cellsSelf-renewalDifferentiationDietary patternsIntestinal diseases
Type
Review Article
Information
Nutrition Research Reviews , Volume 35 , Issue 1 , June 2022 , pp. 150 - 158
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society

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References

O’Keefe, SJD. (2016) Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol 13, 691–706.CrossRefGoogle ScholarPubMed
Schulz, MD, Atay, C, Heringer, J, et al. (2014) High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature 514, 508–512.CrossRefGoogle ScholarPubMed
Beyaz, S, Mana, MD, Roper, J, et al. (2016) High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531, 53–58.CrossRefGoogle ScholarPubMed
Redman, LM, Smith, SR, Burton, JH, et al. (2018) Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab 27, 805–815.CrossRefGoogle ScholarPubMed
Colman, RJ, Beasley, TM, Kemnitz, JW, et al. (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5, 3557.CrossRefGoogle ScholarPubMed
Longo, VD & Fontana, L (2010) Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci 31, 89–98.CrossRefGoogle ScholarPubMed
Rangan, P, Choi, I, Wei, M, et al. (2019) Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology. Cell Rep 26, 2704–2719.CrossRefGoogle Scholar
Cheng, CW, Biton, M, Haber, AL, et al. (2019) Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet. Cell 178, 1115–1131.CrossRefGoogle Scholar
Yousefi, M, Nakauka-Ddamba, A, Berry, CT, et al. (2018) Calorie restriction governs intestinal epithelial regeneration through cell-autonomous regulation of mTORC1 in reserve stem cells. Stem Cell Rep 10, 703–711.CrossRefGoogle ScholarPubMed
Mihaylova, MM, Cheng, CW, Cao, AQ, et al. (2018) Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem Cell 22, 769–778.CrossRefGoogle ScholarPubMed
Igarashi, M & Guarente, L (2016) mTORC1 and SIRT1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 166, 436–450.CrossRefGoogle Scholar
Tinkum, KL, Stemler, KM, White, LS, et al. (2015) Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A 112, 7148–7154.CrossRefGoogle ScholarPubMed
Richmond, CA, Shah, MS, Deary, LT, et al. (2015) Dormant intestinal stem cells are regulated by PTEN and nutritional status. Cell Rep 13, 2403–2411.CrossRefGoogle ScholarPubMed
Barker, N (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Bio 15, 19–33.CrossRefGoogle ScholarPubMed
Barker, N, Bartfeld, S & Clevers, H (2010) Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell 7, 656–670.CrossRefGoogle ScholarPubMed
Wang, Q, Lin, Y, Sheng, X, et al. (2020) Arachidonic acid promotes intestinal regeneration by activating WNT signaling. Stem Cell Rep 15, 374–388.CrossRefGoogle ScholarPubMed
Sorrentino, G, Perino, A, Yildiz, E, et al. (2020) Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration. Gastroenterology 159, 956–968.CrossRefGoogle ScholarPubMed
Saito, Y, Iwatsuki, K, Hanyu, H, et al. (2017) Effect of essential amino acids on enteroids: methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells. Biochem Biophys Res Commun 488, 171–176.CrossRefGoogle ScholarPubMed
Peregrina, K, Houston, M, Daroqui, C, et al. (2015) Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions. Carcinogenesis 36, 25–31.CrossRefGoogle ScholarPubMed
Lee, YS, Kim, TY, Kim, Y, et al. (2018) Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host Microbe 24, 833–846.CrossRefGoogle Scholar
Barker, N, van Es, JH, Kuipers, J, et al. (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007.CrossRefGoogle ScholarPubMed
Hendry, J & Potten, C (1974) Cryptogenic cells and proliferative cells in intestinal epithelium. Int J Radiat Biol Relat Stud Phys Chem Med 25, 583–588.CrossRefGoogle ScholarPubMed
Yan, KS, Chai, LA, Li, X, et al. (2012) The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A 109, 466–471.CrossRefGoogle ScholarPubMed
Montgomery, RK, Carlone, DL, Richmond, CA, et al. (2011) Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci U S A 108, 179–184.CrossRefGoogle ScholarPubMed
Powell, AE, Wang, Y, Li, YN, et al. (2012) The Pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149, 146–158.CrossRefGoogle ScholarPubMed
Sangiorgi, E & Capecchi, MR (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 40, 915–920.CrossRefGoogle ScholarPubMed
Clevers, H (2013) The intestinal crypt, a prototype stem cell compartment. Cell 154, 274–284.CrossRefGoogle ScholarPubMed
von Moltke, J, Ji, M, Liang, HE, et al. (2016) Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221–243.CrossRefGoogle ScholarPubMed
Sato, T, van Es, JH, Snippert, HJ, et al. (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415–418.CrossRefGoogle ScholarPubMed
Tian, H, Biehs, B, Warming, S, et al. (2011) A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255–259.CrossRefGoogle ScholarPubMed
Sanders, MA & Majumdar, APN. (2011) Colon cancer stem cells: implications in carcinogenesis. Front Biosci 16, 1651–1662.CrossRefGoogle ScholarPubMed
Barker, N, Ridgway, RA, van Es, JH, et al. (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611.CrossRefGoogle ScholarPubMed
Rhodes, JM & Campbell, BJ. (2002) Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. Trends Mol Med 8, 10–16.CrossRefGoogle ScholarPubMed
Vermeulen, L, Todaro, M, Mello, FD, et al. (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A 105, 13427–13432.CrossRefGoogle Scholar
Khaloian, S & Rath, E. (2020) Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn’s disease recurrence. Gut 69, 1939–1951.CrossRefGoogle ScholarPubMed
Schmitt, M, Schewe, M, Sacchetti, A, et al. (2018) Paneth cells respond to inflammation and contribute to tissue regeneration by acquiring stem-like features through SCF/c-Kit signaling. Cell Rep 24, 2312–2328.CrossRefGoogle ScholarPubMed
Yan, KS, Chia, LA, Li, XN, et al. (2012) The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A 109, 466–471.CrossRefGoogle ScholarPubMed
El-Salhy, M (2020) Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 26, 1427–1438.CrossRefGoogle ScholarPubMed
Igarashi, M, Miura, M, Williams, E, et al. (2019) NAD(+) supplementation rejuvenates aged gut adult stem cells. Aging Cell 18, e12935.CrossRefGoogle ScholarPubMed
Saxton, RA & Sabatini, DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168, 960–976.CrossRefGoogle Scholar
Zoncu, R, Efeyan, A & Sabatini, DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Bio 12, 21–35.CrossRefGoogle ScholarPubMed
Kapuria, S, Karpac, J, Biteau, B, et al. (2012) Notch-mediated suppression of TSC2 expression regulates cell differentiation in the drosophila intestinal stem cell lineage. PLoS Genet 8, e1003045.CrossRefGoogle Scholar
Kaur, H & Moreau, R (2019) Role of mTORC1 in intestinal epithelial repair and tumorigenesis. Cell Mol Life Sci 76, 2525–2546.CrossRefGoogle ScholarPubMed
Sampson, LL, Davis, AK, Grogg, MW, et al. (2016) mTOR disruption causes intestinal epithelial cell defects and intestinal atrophy postinjury in mice. FASEB J 30, 1263–1275.CrossRefGoogle Scholar
He, D, Wu, H, Xiang, J, et al. (2020) Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway. Nat Commun 11, 37.CrossRefGoogle Scholar
Pentinmikko, N, Iqbal, S, Mana, M, et al. (2019) Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. Nature 571, 398–402.CrossRefGoogle ScholarPubMed
Gao, YJ, Yan, Y, Tripathi, S, et al. (2020) LKB1 represses ATOH1 via PDK4 and energy metabolism and regulates intestinal stem cell fate. Gastroenterology 158, 1389–1401.CrossRefGoogle ScholarPubMed
Finkel, T, Deng, CX & Mostoslavsky, R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460, 587–591.CrossRefGoogle ScholarPubMed
Brandauer, J, Vienberg, SG, Andersen, MA, et al. (2013) AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle. J Physiol 591, 5207–5220.CrossRefGoogle ScholarPubMed
Johnson, SC, Rabinovitch, PS & Kaeberlein, M. (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493, 338–345.CrossRefGoogle Scholar
Yilmaz, Ö H, Katajisto, P, Lamming, DW, et al. (2012) mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486, 490–495.CrossRefGoogle Scholar
Cheng, CW, Adams, GB, Perin, L, et al. (2014) Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell 14, 810–823.CrossRefGoogle ScholarPubMed
Longo, VD & Mattson, MP (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab 19, 181–192.CrossRefGoogle ScholarPubMed
de la Cruz Bonilla, M, Stemler, K, Jeter-Jones, S, et al. (2019) Fasting reduces intestinal radiotoxicity, enabling dose-escalated radiation therapy for pancreatic cancer. Int J Radiat Oncol Biol Phys 105, 537–547.CrossRefGoogle ScholarPubMed
Andres, SF, Santoro, MA, Mah, AT, et al. (2015) Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs. Am J Physiol Gastrointest Liver Physiol 308, 100–111.CrossRefGoogle ScholarPubMed
Mah, AT, Van Landeghem, L, Gavin, HE, et al. (2014) Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1. Endocrinology 155, 3302–3314.CrossRefGoogle ScholarPubMed
Mao, J, Hu, X, Xiao, Y, et al. (2013) Overnutrition stimulates intestinal epithelium proliferation through β-catenin signaling in obese mice. Diabetes 62, 3736–3746.CrossRefGoogle ScholarPubMed
Baldassano, S, Amato, A, Cappello, F, et al. (2013) Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet. J Endocrinol 217, 11–20.CrossRefGoogle Scholar
Mihaylova, MM, Sabatini, DM & Yilmaz, OH (2014) Dietary and metabolic control of stem cell function in physiology and cancer. Cell Stem Cell 14, 292–305.CrossRefGoogle ScholarPubMed
Newman, JC, Covarrubias, AJ, Zhao, MH, et al. (2017) Ketogenic diet reduces midlife mortality and improves memory in aging mice. Cell Metab 26, 547–557.CrossRefGoogle ScholarPubMed
Gebert, N, Cheng, CW, Kirkpatrick, JM, et al. (2020) Region-specific proteome changes of the intestinal epithelium during aging and dietary restriction. Cell Rep 31, 107565.CrossRefGoogle Scholar
Newman, JC & Verdin, E (2014) Ketone bodies as signaling metabolites. Trends Endocrinol Metab 25, 42–52.CrossRefGoogle ScholarPubMed
Wang, Q, Zhou, Y, Rychahou, P, et al. (2017) Ketogenesis contributes to intestinal cell differentiation. Cell Death Differ 24, 458–468.CrossRefGoogle ScholarPubMed
Palmeira, JS, Varela, AT, Rolo, AP, et al. (2014) High-fat and obesogenic diets: current and future strategies to fight obesity and diabetes. Genes Nutr 9, 406.CrossRefGoogle Scholar
Zhang, X, Jin, Q & Li, HJ. (2017) High sugar diet disrupts gut homeostasis though JNK and STAT pathways in Drosophila. Biochem Biophys Res Commun 487, 910–916.CrossRefGoogle ScholarPubMed
Obata, F, Tsuda-Sakurai, K, Yamazaki, T, et al. (2018) Nutritional control of stem cell division through S-Adenosylmethionine in drosophila intestine. Dev Cell 44, 741–751.CrossRefGoogle ScholarPubMed
Gibbons, GS, Owens, SR, Fearon, ER, et al. (2015) Regulation of Wnt signaling target gene expression by the histone methyltransferase DOT1L. ACS Chem Biol 10, 109–114.CrossRefGoogle ScholarPubMed
Hou, Q, Dong, Y, Yu, Q, et al. (2020) Regulation of the Paneth cell niche by exogenous L-arginine couples the intestinal stem cell function. FASEB J 34, 10299–10315.CrossRefGoogle ScholarPubMed
Deng, H, Gerencser, AA & Jasper, H. (2015) Signal integration by Ca(2+) regulates intestinal stem-cell activity. Nature 528, 212–217.CrossRefGoogle ScholarPubMed
Moore, SR, Guedes, MM, Costa, TB, et al. (2015) Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids. Am J Physiol Gastrointest Liver Physiol 308, 831–839.CrossRefGoogle ScholarPubMed
Zhu, M, Qin, YC, Gao, CQ, et al. (2019) Extracellular glutamate-induced mTORC1 activation via the IR/IRS/PI3K/Akt pathway enhances the expansion of porcine intestinal stem cells. J Agric Food Chem 67, 9510–9521.CrossRefGoogle ScholarPubMed
Stine, RR, Sakers, AP, TeSlaa, T, et al. (2019) PRDM16 maintains homeostasis of the intestinal epithelium by controlling region-specific metabolism. Cell Stem Cell 25, 830–845.CrossRefGoogle ScholarPubMed
Chen, L, Vasoya, RP, Toke, NH, et al. (2019) HNF4 regulates fatty acid oxidation and is required for renewal of intestinal stem cells in mice. Gastroenterology 158, 985–999.CrossRefGoogle ScholarPubMed
Pálmer, HG, González-Sancho, JM, Espada, J, et al. (2001) Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol 154, 369–387.CrossRefGoogle ScholarPubMed
Wang, Z, Li, J, Wang, Y, et al. (2020) Dietary vitamin A affects growth performance, intestinal development, and functions in weaned piglets by affecting intestinal stem cells. J Anim Sci 98, skaa020.CrossRefGoogle Scholar
Wahlström, A, Sayin, S, Marschall, H, et al. (2016) Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 24, 41–50.CrossRefGoogle ScholarPubMed
Hegyi, P, Maléth, J, Walters, J, et al. (2018) Guts and gall: bile acids in regulation of intestinal epithelial function in health and disease. Physiol Rev 98, 1983–2023.CrossRefGoogle ScholarPubMed
Farhana, L, Nangia-Makker, P, Arbit, E, et al. (2016) Bile acid: a potential inducer of colon cancer stem cells. Stem Cell Res Ther 7, 181.CrossRefGoogle ScholarPubMed
Fu, T, Coulter, S, Yoshihara, E, et al. (2019) FXR regulates intestinal cancer stem cell proliferation. Cell 176, 1098–1112.CrossRefGoogle ScholarPubMed
Hou, Q, Ye, L, Liu, H, et al. (2018) Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death Differ 25, 1657–1670.CrossRefGoogle ScholarPubMed
Wu, H, Xie, S, Miao, J, et al. (2020) Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa. Gut Microbes 11, 997–1014.CrossRefGoogle ScholarPubMed
Kaiko, GE, Ryu, SH, Koues, OI, et al. (2016) The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165, 1708–1720.CrossRefGoogle ScholarPubMed
Yin, X, Farin, HF, van Es, JH, et al. (2014) Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny. Nat Methods 11, 106–112.CrossRefGoogle Scholar
Metidji, A, Omenetti, S, Crotta, S, et al. (2018) The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity. Immunity 49, 353–362.CrossRefGoogle ScholarPubMed
Park, JH, Lee, JM, Lee, EJ, et al. (2018) Indole-3-Carbinol promotes goblet-cell differentiation regulating Wnt and Notch signaling pathways AhR-dependently. Mol Cells 41, 290–300.Google ScholarPubMed
Burrin, D, Sangild, PT, Stoll, B, et al. (2020). Translational advances in pediatric nutrition and gastroenterology: new insights from pig models. Annu Rev Anim Biosci 8, 321–354.CrossRefGoogle ScholarPubMed