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Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function

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Abstract

Frequent exposure to mechanistic damages, pathological ingression, and chronic inflammation leads to recurrent cell death in the gut epithelium. Intestinal stem cells (ISCs) that reside in crypt-specific niches have an unprecedented role in gut epithelium renewal. ISC also facilitates the formation of mature intestinal epithelial cells (IECs) through regular differentiation and renewal in short turnover cycles. Interestingly, oxidative stress (OS) prevalent in the gut has a dominant role in the regulation of ISC proliferation and development. However, it is unclear, which axis OS controls the cellular signaling and underlying molecular mechanism to drive ISC turnover and regeneration cycle. Therefore, this review provides a comprehensive overview of the present understanding of OS generation in the gut, relatively directing the ISC development and regeneration under a conditional cellular environment. Additionally, the focus has been drawn on intestinal nutritional state and its related alteration on OS and its effect on ISCs. Moreover, recent findings and new approaches are emphasized herewith to enhance the present understanding of the mechanisms that direct universal ISC characteristics.

Graphical abstract

Intestinal stem cells (ISC) form the basis of all repair mechanisms that help in the proliferation of the gut through their constant renewal and replacement. This activity is closely regulated in the ISC niche and is modulated by several extrinsic as well as intrinsic factors. Reactive Oxygen Species (ROS) form one of the major factors that influence ISC formation. The levels of ROS in the gut influence stem cell renewal ROS itself however is further influenced by several other factors such as the microbiota concerning the gut and immune cells which in turn also influence one another by various cross-talk mechanisms. Diet also forms an important part of this crosstalk. It also regulates the levels of ROS in the gut and helps in the proliferation of the ISC cells and their overall turnover rate.

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References

  1. Lee, K.-A., Kim, S.-H., Kim, E.-K., Ha, E.-M., You, H., Kim, B., Kim, M.-J., Kwon, Y., Ryu, J.-H., & Lee, W.-J. (2013). Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell, 153(4), 797–811.

    Article  CAS  PubMed  Google Scholar 

  2. Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R., & Gordon, J. I. (2008). Worlds within worlds: Evolution of the vertebrate gut microbiota. Nature Reviews Microbiology, 6(10), 776–788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Savage, D. C. (1977). Microbial ecology of the gastrointestinal tract. Annual Review of Microbiology, 31(1), 107–133.

    Article  CAS  PubMed  Google Scholar 

  4. Artis, D. (2008). Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nature Reviews Immunology, 8(6), 411–420.

    Article  CAS  PubMed  Google Scholar 

  5. Beutler, B. (2004). Inferences, questions and possibilities in Toll-like receptor signalling. Nature, 430(6996), 257–263.

    Article  CAS  PubMed  Google Scholar 

  6. Allaire, J. M., Crowley, S. M., Law, H. T., Chang, S.-Y., Ko, H.-J., & Vallance, B. A. (2018). The intestinal epithelium: Central coordinator of mucosal immunity. Trends in Immunology, 39(9), 677–696.

    Article  CAS  PubMed  Google Scholar 

  7. Gehart, H., & Clevers, H. (2019). Tales from the crypt: New insights into intestinal stem cells. Nature Reviews Gastroenterology & Hepatology, 16(1), 19–34.

    Article  Google Scholar 

  8. Yilmaz, B., & Li, H. (2018). Gut microbiota and iron: The crucial actors in health and disease. Pharmaceuticals, 11(4), 98.

    Article  CAS  PubMed Central  Google Scholar 

  9. Montgomery, R. K., & Breault, D. T. (2008). Small intestinal stem cell markers. Journal of Anatomy, 213(1), 52–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Van der Flier, L. G., Sabates-Bellver, J., Oving, I., Haegebarth, A., De Palo, M., Anti, M., Van Gijn, M. E., Suijkerbuijk, S., Van de Wetering, M., & Marra, G. (2007). The intestinal Wnt/TCF signature. Gastroenterology, 132(2), 628–632.

    Article  PubMed  CAS  Google Scholar 

  11. Powell, A. E., Wang, Y., Li, Y., Poulin, E. J., Means, A. L., Washington, M. K., Higginbotham, J. N., Juchheim, A., Prasad, N., & Levy, S. E. (2012). The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell, 149(1), 146–158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wong, V. W., Stange, D. E., Page, M. E., Buczacki, S., Wabik, A., Itami, S., Van De Wetering, M., Poulsom, R., Wright, N. A., & Trotter, M. W. (2012). Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nature Cell Biology, 14(4), 401–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bae, Y. S., Choi, M. K., & Lee, W.-J. (2010). Dual oxidase in mucosal immunity and host–microbe homeostasis. Trends in Immunology, 31(7), 278–287.

    Article  CAS  PubMed  Google Scholar 

  14. Lemaitre, B., & Hoffmann, J. (2007). The host defense of Drosophila melanogaster. Annual Review of Immunology, 25, 697–743.

    Article  CAS  PubMed  Google Scholar 

  15. Ha, E.-M., Lee, K.-A., Seo, Y. Y., Kim, S.-H., Lim, J.-H., Oh, B.-H., Kim, J., & Lee, W.-J. (2009). Coordination of multiple dual oxidase–regulatory pathways in responses to commensal and infectious microbes in drosophila gut. Nature Immunology, 10(9), 949–957.

    Article  CAS  PubMed  Google Scholar 

  16. Ha, E.-M., Oh, C.-T., Bae, Y. S., & Lee, W.-J. (2005). A direct role for dual oxidase in Drosophila gut immunity. Science, 310(5749), 847–850.

    Article  CAS  PubMed  Google Scholar 

  17. Burtenshaw, D., Hakimjavadi, R., Redmond, E. M., & Cahill, P. A. (2017). Nox, reactive oxygen species and regulation of vascular cell fate. Antioxidants, 6(4), 90.

    Article  PubMed Central  CAS  Google Scholar 

  18. Atashi, F., Modarressi, A., & Pepper, M. S. (2015). The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: A review. Stem Cells and Development, 24(10), 1150–1163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vlasits, J., Jakopitsch, C., Bernroitner, M., Zamocky, M., Furtmüller, P. G., & Obinger, C. (2010). Mechanisms of catalase activity of heme peroxidases. Archives of Biochemistry and Biophysics, 500(1), 74–81.

    Article  CAS  PubMed  Google Scholar 

  20. Zhu, G., Hu, J., & Xi, R. (2021). The cellular niche for intestinal stem cells: A team effort. Cell Regeneration, 10(1), 1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Santos, A. J., Lo, Y.-H., Mah, A. T., & Kuo, C. J. (2018). The intestinal stem cell niche: Homeostasis and adaptations. Trends in Cell Biology, 28(12), 1062–1078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Umar, S. (2010). Intestinal stem cells. Current Gastroenterology Reports, 12(5), 340–348.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Xing, P. Y., Pettersson, S., & Kundu, P. (2020). Microbial metabolites and intestinal stem cells tune intestinal homeostasis. Proteomics, 20(5–6), 1800419.

    Article  CAS  Google Scholar 

  24. Hou, Q., Ye, L., Huang, L., & Yu, Q. (2017). The research progress on intestinal stem cells and its relationship with intestinal microbiota. Frontiers in Immunology, 8, 599.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Holloway, E., Czerwinski, M., Tsai, Y., Wu, J. H., Wu, A., Childs, C. J., Walton, K. D., Sweet, C. W., Yu, Q., & Glass, I. (2021). Mapping development of the human intestinal niche at single-cell resolution. Cell Stem Cell, 28(3), 568-580. e4.

    Article  CAS  PubMed  Google Scholar 

  26. Barker, N., Van Es, J. H., Kuipers, J., Kujala, P., Van Den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., & Peters, P. J. (2007). Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature, 449(7165), 1003–1007.

    Article  CAS  PubMed  Google Scholar 

  27. Rees, W. D., Tandun, R., Yau, E., Zachos, N. C., & Steiner, T. S. (2020). Regenerative intestinal stem cells induced by acute and chronic injury: The saving grace of the epithelium? Frontiers in Cell and Developmental Biology, 8, 1333.

    Article  Google Scholar 

  28. Bamba, S., Andoh, A., Yasui, H., Makino, J., Kim, S., & Fujiyama, Y. (2003). Regulation of IL-11 expression in intestinal myofibroblasts: role of c-Jun AP-1-and MAPK-dependent pathways. American Journal of Physiology-Gastrointestinal and Liver Physiology, 285(3), G529–G538.

    Article  CAS  PubMed  Google Scholar 

  29. Murata, K., Jadhav, U., Madha, S., van Es, J., Dean, J., Cavazza, A., Wucherpfennig, K., Michor, F., Clevers, H., & Shivdasani, R. A. (2020). Ascl2-dependent cell dedifferentiation drives regeneration of ablated intestinal stem cells. Cell Stem Cell, 26(3), 377-390. e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Minamide, K., Sato, T., Nakanishi, Y., Ohno, H., Kato, T., Asano, J., & Ohteki, T. (2020). IRF2 maintains the stemness of colonic stem cells by limiting physiological stress from interferon. Scientific Reports, 10(1), 1–12.

    Article  CAS  Google Scholar 

  31. Metcalfe, C., Kljavin, N. M., Ybarra, R., & de Sauvage, F. J. (2014). Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell, 14(2), 149–159.

    Article  CAS  PubMed  Google Scholar 

  32. Miguel, J. C., Maxwell, A. A., Hsieh, J. J., Harnisch, L. C., Al Alam, D., Polk, D. B., Lien, C.-L., Watson, A. J., & Frey, M. R. (2017). Epidermal growth factor suppresses intestinal epithelial cell shedding through a MAPK-dependent pathway. Journal of Cell Science, 130(1), 90–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Koren, E., Yosefzon, Y., Ankawa, R., Soteriou, D., Jacob, A., Nevelsky, A., Ben-Yosef, R., Bar-Sela, G., & Fuchs, Y. (2018). ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nature Communications, 9(1), 1–17.

    Article  CAS  Google Scholar 

  34. Patankar, J. V., & Becker, C. (2020). Cell death in the gut epithelium and implications for chronic inflammation. Nature Reviews Gastroenterology & Hepatology, 17(9), 543–556.

    Article  Google Scholar 

  35. Chen, Y., Tsai, Y.-H., Tseng, B.-J., & Tseng, S.-H. (2019). Influence of growth hormone and glutamine on intestinal stem cells: A narrative review. Nutrients, 11(8), 1941.

    Article  CAS  PubMed Central  Google Scholar 

  36. Veldman, R. J., Klappe, K., Hoekstra, D., & Kok, J. W. (1998). Interferon-γ-Induced Differentiation and Apoptosis of HT29 Cells: Dissociation of (Glucosyl) ceramide Signaling. Biochemical and Biophysical Research Communications, 247(3), 802–808.

    Article  CAS  PubMed  Google Scholar 

  37. Litvak, D. A., Evers, B. M., Hwang, K. O., Hellmich, M. R., Ko, T. C., & Townsend, C. M., Jr. (1998). Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21Waf1/Cip1 and p27Kip1. Surgery, 124(2), 161–170.

    Article  CAS  PubMed  Google Scholar 

  38. Banerjee, A., Herring, C. A., Chen, B., Kim, H., Simmons, A. J., Southard-Smith, A. N., Allaman, M. M., White, J. R., Macedonia, M. C., & Mckinley, E. T. (2020). Succinate produced by intestinal microbes promotes specification of tuft cells to suppress ileal inflammation. Gastroenterology, 159(6), 2101-2115. e5.

    Article  CAS  PubMed  Google Scholar 

  39. van Es, J. H., & Clevers, H. (2014). Paneth cells. Current Biology, 24(12), R547–R548.

    Article  PubMed  CAS  Google Scholar 

  40. Savage, D. C., & Blumershine, R. V. (1974). Surface-surface associations in microbial communities populating epithelial habitats in the murine gastrointestinal ecosystem: Scanning electron microscopy. Infection and Immunity, 10(1), 240–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tropini, C., Earle, K. A., Huang, K. C., & Sonnenburg, J. L. (2017). The gut microbiome: Connecting spatial organization to function. Cell Host & Microbe, 21(4), 433–442.

    Article  CAS  Google Scholar 

  42. Bhattacharyya, A., Chattopadhyay, R., Mitra, S., Crowe, S. E. J. P., & r. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological Reviews, 94(2), 329–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ballard, J. W. O., & Towarnicki, S. G. (2020). Mitochondria, the gut microbiome and ROS. Cellular Signalling, 75, 109737.

    Article  CAS  PubMed  Google Scholar 

  44. Lee, W.-J. (2009). Bacterial-modulated host immunity and stem cell activation for gut homeostasis. Genes & Development, 23(19), 2260–2265.

    Article  CAS  Google Scholar 

  45. Bhattacharyya, A., Chattopadhyay, R., Mitra, S., & Crowe, S. E. (2014). Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological Reviews, 94(2), 329–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Maraldi, T., Angeloni, C., Prata, C., & Hrelia, S. (2021). NADPH oxidases: redox regulators of stem cell fate and function. Antioxidants, 10(6), 973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Campbell, E. L., & Colgan, S. P. (2019). Control and dysregulation of redox signalling in the gastrointestinal tract. Nature Reviews Gastroenterology & Hepatology, 16(2), 106–120.

    Article  Google Scholar 

  48. Chen, Z., Luo, J., Li, J., Kim, G., Chen, E. S., Xiao, S., Snapper, S. B., Bao, B., An, D., & Blumberg, R. S. (2021). Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion. Journal of Experimental Medicine, 218(9), e20210324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Morris, O., & Jasper, H. (2021). Reactive Oxygen Species in intestinal stem cell metabolism, fate and function. Free Radical Biology and Medicine, 166, 140–146.

    Article  CAS  PubMed  Google Scholar 

  50. Luo, H., Chiang, H.-H., Louw, M., Susanto, A., & Chen, D. (2017). Nutrient sensing and the oxidative stress response. Trends in Endocrinology & Metabolism, 28(6), 449–460.

    Article  CAS  Google Scholar 

  51. Wang, D., Odle, J., & Liu, Y. (2021). Metabolic regulation of intestinal stem cell homeostasis. Trends in Cell Biology, 31, 325–327.

    Article  CAS  PubMed  Google Scholar 

  52. Conway, J., & Duggal, N. A. (2021). Ageing of the gut microbiome: potential influences on immune senescence and inflammageing. Ageing Research Reviews, 68, 101323.

    Article  CAS  PubMed  Google Scholar 

  53. Shyh-Chang, N., & Ng, H.-H. (2017). The metabolic programming of stem cells. Genes & Development, 31(4), 336–346.

    Article  CAS  Google Scholar 

  54. Lamberti, M. J., Pansa, M. F., Vera, R. E., Fernández-Zapico, M. E., RumieVittar, N. B., & Rivarola, V. A. (2017). Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy. PloS one, 12(5), e0177801.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Minatel, I. O., Francisqueti, F. V., Corrêa, C. R., & Lima, G. P. P. (2016). Antioxidant activity of γ-oryzanol: A complex network of interactions. International Journal of Molecular Sciences, 17(8), 1107.

    Article  PubMed Central  CAS  Google Scholar 

  56. Wang, Z., Li, S., Cao, Y., Tian, X., Zeng, R., Liao, D.-F., & Cao, D. (2016). Oxidative stress and carbonyl lesions in ulcerative colitis and associated colorectal cancer. Oxidative Medicine and Cellular Longevity, 2016, 9875298.

    Article  PubMed  Google Scholar 

  57. Shao, Y., Wang, K., Xiong, X., Liu, H., Zhou, J., Zou, L., Qi, M., Liu, G., Huang, R., & Tan, Z. (2021). The landscape of interactions between hypoxia-inducible factors and reactive oxygen species in the gastrointestinal tract. Oxidative Medicine and Cellular Longevity, 2021, 8893663.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Liu, Y., Wang, C., Wang, Y., Ma, Z., Xiao, J., McClain, C., Li, X., & Feng, W. (2012). Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells. Toxicology and Applied Pharmacology, 264(2), 212–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fan, C., Han, J., Liu, X., Zhang, F., Long, Y., & Xie, Q. (2019). Modulation of hypoxia-inducible factor-1α/cyclo-oxygenase-2 pathway associated with attenuation of intestinal mucosa inflammatory damage by Acanthopanax senticosus polysaccharides in lipopolysaccharide-challenged piglets. British Journal of Nutrition, 122(6), 666–675.

    Article  CAS  PubMed  Google Scholar 

  60. Radisky, D. C., Levy, D. D., Littlepage, L. E., Liu, H., Nelson, C. M., Fata, J. E., Leake, D., Godden, E. L., Albertson, D. G., Nieto, M. A., Werb, Z., & Bissell, M. J. (2005). Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature, 436(7047), 123–127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McCarthy, N., Kraiczy, J., & Shivdasani, R. A. (2020). Cellular and molecular architecture of the intestinal stem cell niche. Nature Cell Biology, 22(9), 1033–1041.

    Article  CAS  PubMed  Google Scholar 

  62. Ashton, G. H., Morton, J. P., Myant, K., Phesse, T. J., Ridgway, R. A., Marsh, V., Wilkins, J. A., Athineos, D., Muncan, V., Kemp, R., Neufeld, K., Clevers, H., Brunton, V., Winton, D. J., Wang, X., Sears, R. C., Clarke, A. R., Frame, M. C., & Sansom, O. J. (2010). Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Developmental Cell, 19(2), 259–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Myant, K. B., Cammareri, P., McGhee, E. J., Ridgway, R. A., Huels, D. J., Cordero, J. B., Schwitalla, S., Kalna, G., Ogg, E. L., Athineos, D., Timpson, P., Vidal, M., Murray, G. I., Greten, F. R., Anderson, K. I., & Sansom, O. J. (2013). ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell, 12(6), 761–773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sánchez-de-Diego, C., Valer, J. A., Pimenta-Lopes, C., Rosa, J. L., & Ventura, F. (2019). Interplay between BMPs and reactive oxygen species in cell signaling and pathology. Biomolecules, 9(10), 534.

    Article  PubMed Central  CAS  Google Scholar 

  65. Takemura, M., Bowden, N., Lu, Y.-S., Nakato, E., O’Connor, M. B., & Nakato, H. (2021). Drosophila MOV10 regulates the termination of midgut regeneration. Genetics, 218(1), iyab031.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Lu, C., Zhou, D., Wang, Q., Liu, W., Yu, F., Wu, F., & Chen, C. (2020). Crosstalk of microRNAs and oxidative stress in the pathogenesis of cancer. Oxidative Medicine and Cellular Longevity, 2020, 2415324.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Bigarella, C. L., Liang, R., & Ghaffari, S. (2014). Stem cells and the impact of ROS signaling. Development, 141(22), 4206–4218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. van der Vliet, A., Danyal, K., & Heppner, D. E. (2018). Dual oxidase: A novel therapeutic target in allergic disease. British Journal of Pharmacology, 175(9), 1401–1418.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Wang, Z., Litterio, M. C., Müller, M., Vauzour, D., & Oteiza, P. I. (2020). (-)-Epicatechin and NADPH oxidase inhibitors prevent bile acid-induced Caco-2 monolayer permeabilization through ERK1/2 modulation. Redox Biology, 28, 101360.

    Article  CAS  PubMed  Google Scholar 

  70. Dang, P.M.-C., Rolas, L., & El Benna, J. (2020). The dual role of ROS-generating NADPH oxidases in gastrointestinal inflammation and therapeutic perspectives. Antioxidants and Redox Signaling, 33(5), 354–373.

    Article  CAS  PubMed  Google Scholar 

  71. Du, Q., Liao, Q., Chen, C., Yang, X., Xie, R., & Xu, J. (2019). The role of transient receptor potential vanilloid 1 in common diseases of the digestive tract and the cardiovascular and respiratory system. Frontiers in Physiology, 10, 1064.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Yamamoto, T., Nakano, H., Shiomi, K., Wanibuchi, K., Masui, H., Takahashi, T., Urano, Y., & Kamata, T. (2018). Identification and characterization of a novel NADPH oxidase 1 (Nox1) inhibitor that suppresses proliferation of colon and stomach cancer cells. Biological and Pharmaceutical Bulletin, 41(3), 419–426.

    Article  CAS  PubMed  Google Scholar 

  73. Reis, J., Massari, M., Marchese, S., Ceccon, M., Aalbers, F. S., Corana, F., Valente, S., Mai, A., Magnani, F., & Mattevi, A. (2020). A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action. Redox Biology, 32, 101466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Altenhöfer, S., Kleikers, P. W., Radermacher, K. A., Scheurer, P., Hermans, J. R., Schiffers, P., Ho, H., Wingler, K., & Schmidt, H. H. (2012). The NOX toolbox: Validating the role of NADPH oxidases in physiology and disease. Cellular and Molecular Life Sciences, 69(14), 2327–2343.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Cifuentes-Pagano, E., Csanyi, G., & Pagano, P. J. (2012). NADPH oxidase inhibitors: A decade of discovery from Nox2ds to HTS. Cellular and Molecular Life Sciences, 69(14), 2315–2325.

    Article  CAS  PubMed  Google Scholar 

  76. Mårtensson, J., Jain, A., & Meister, A. (1990). Glutathione is required for intestinal function. Proceedings of the National Academy of Sciences, 87(5), 1715–1719.

    Article  Google Scholar 

  77. Cui, L., Takagi, Y., Wasa, M., Sando, K., Khan, J., & Okada, A. (1999). Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats. The Journal of Nutrition, 129(4), 792–798.

    Article  CAS  PubMed  Google Scholar 

  78. Kim, J.-W., Choi, C. S., Kim, K. C., Park, J. H., Seung, H., Joo, S. H., Yang, S. M., Shin, C. Y., & Park, S. H. (2013). Gastrointestinal tract abnormalities induced by prenatal valproic Acid exposure in rat offspring. Toxicological Research, 29(3), 173–179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Silva, M., Aires, C., Luis, P., Ruiter, J., IJlst, L., Duran, M., Wanders, R., & De Almeida, I. T. (2008). Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review. Journal of Inherited Metabolic Disease, 31(2), 205–216.

    Article  CAS  PubMed  Google Scholar 

  80. Nigro, G., & Sansonetti, P. J. (2015). Microbiota and gut stem cells cross-talks: A new view of epithelial homeostasis. Current Stem Cell Reports, 1(1), 48–52.

    Article  Google Scholar 

  81. Bhat, M. I., & Kapila, R. (2017). Dietary metabolites derived from gut microbiota: Critical modulators of epigenetic changes in mammals. Nutrition Reviews, 75(5), 374–389.

    Article  PubMed  Google Scholar 

  82. Fan, Y., & Pedersen, O. (2021). Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology, 19(1), 55–71.

    Article  CAS  PubMed  Google Scholar 

  83. Lee, W.-J., & Kim, S.-H. (2014). Role of DUOX in gut inflammation: Lessons from Drosophila model of gut-microbiota interactions. Frontiers in Cellular and Infection Microbiology, 3, 116.

    PubMed  PubMed Central  Google Scholar 

  84. Jones, R. M., Mercante, J. W., & Neish, A. S. (2012). Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. Current Medicinal Chemistry, 19(10), 1519–1529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jasper, H. (2020). Intestinal stem cell aging: Origins and interventions. Annual Review of Physiology, 82, 203–226.

    Article  CAS  PubMed  Google Scholar 

  86. Frese, S. A., Hutkins, R. W., & Walter, J. (2012). Comparison of the colonization ability of autochthonous and allochthonous strains of lactobacilli in the human gastrointestinal tract. Advances in Microbiology, 2(03), 399.

    Article  Google Scholar 

  87. Sansonetti, P. J. (2004). War and peace at mucosal surfaces. Nature Reviews Immunology, 4(12), 953–964.

    Article  CAS  PubMed  Google Scholar 

  88. Ethridge, A. D., Bazzi, M. H., Lukacs, N. W., & Huffnagle, G. B. (2021). Interkingdom communication and regulation of mucosal immunity by the microbiome. The Journal of Infectious Diseases, 223(Supplement_3), S236–S240.

    Article  CAS  PubMed  Google Scholar 

  89. Bersch, K. L., DeMeester, K. E., Zagani, R., Chen, S., Wodzanowski, K. A., Liu, S., Mashayekh, S., Reinecker, H.-C., & Grimes, C. L. (2021). Bacterial peptidoglycan fragments differentially regulate innate immune signaling. ACS Central Science, 7(4), 688–696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Tang, R., Huang, W., Guan, J., Liu, Q., Beerntsen, B. T., & Ling, E. (2021). Drosophila H2Av negatively regulates the activity of the IMD pathway via facilitating Relish SUMOylation. PLoS Genetics, 17(8), e1009718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fink, C., Hoffmann, J., Knop, M., Li, Y., Isermann, K., & Roeder, T. (2016). Intestinal FoxO signaling is required to survive oral infection in Drosophila. Mucosal Immunology, 9(4), 927–936.

    Article  CAS  PubMed  Google Scholar 

  92. Lhocine, N., Ribeiro, P. S., Buchon, N., Wepf, A., Wilson, R., Tenev, T., Lemaitre, B., Gstaiger, M., Meier, P., & Leulier, F. (2008). PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host & Microbe, 4(2), 147–158.

    Article  CAS  Google Scholar 

  93. Paredes, J. C., Welchman, D. P., Poidevin, M., & Lemaitre, B. (2011). Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity, 35(5), 770–779.

    Article  CAS  PubMed  Google Scholar 

  94. Thevenon, D., Engel, E., Avet-Rochex, A., Gottar, M., Bergeret, E., Tricoire, H., Benaud, C., Baudier, J., Taillebourg, E., & Fauvarque, M.-O. (2009). The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to prevent constitutive immune signaling. Cell Host & Microbe, 6(4), 309–320.

    Article  CAS  Google Scholar 

  95. Edens, W. A., Sharling, L., Cheng, G., Shapira, R., Kinkade, J. M., Lee, T., Edens, H. A., Tang, X., Sullards, C., & Flaherty, D. B. (2001). Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. Journal of Cell Biology, 154(4), 879–892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kumar, S., Molina-Cruz, A., Gupta, L., Rodrigues, J., & Barillas-Mury, C. (2010). A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae. Science, 327(5973), 1644–1648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Shao, M. X., & Nadel, J. A. (2005). Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proceedings of the National Academy of Sciences, 102(3), 767–772.

    Article  CAS  Google Scholar 

  98. Boumard, B., & Bardin, A. J. (2021). An amuse-bouche of stem cell regulation: Underlying principles and mechanisms from adult Drosophila intestinal stem cells. Current Opinion in Cell Biology, 73, 58–68.

    Article  CAS  PubMed  Google Scholar 

  99. Buchon, N., Broderick, N. A., Chakrabarti, S., & Lemaitre, B. (2009). Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes & development, 23(19), 2333–2344.

    Article  CAS  Google Scholar 

  100. Rodríguez-Colman, M. J., Schewe, M., Meerlo, M., Stigter, E., Gerrits, J., Pras-Raves, M., Sacchetti, A., Hornsveld, M., Oost, K. C., & Snippert, H. J. (2017). Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature, 543(7645), 424–427.

    Article  PubMed  CAS  Google Scholar 

  101. Lee, Y.-S., Kim, T.-Y., Kim, Y., Lee, S.-H., Kim, S., Kang, S. W., Yang, J.-Y., Baek, I.-J., Sung, Y. H., & Park, Y.-Y. (2018). Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host & Microbe, 24(6), 833-846. e6.

    Article  CAS  Google Scholar 

  102. Jones, R. M., Luo, L., Ardita, C. S., Richardson, A. N., Kwon, Y. M., Mercante, J. W., Alam, A., Gates, C. L., Wu, H., & Swanson, P. A. (2013). Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species. The EMBO Journal, 32(23), 3017–3028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Patel, P. H., Pénalva, C., Kardorff, M., Roca, M., Pavlović, B., Thiel, A., Teleman, A. A., & Edgar, B. A. (2019). Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut. Nature Communications, 10(1), 1–14.

    Article  CAS  Google Scholar 

  104. Sorrentino, G., Perino, A., Yildiz, E., El Alam, G., Sleiman, M. B., Gioiello, A., Pellicciari, R., & Schoonjans, K. (2020). Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration. Gastroenterology, 159(3), 956-968. e8.

    Article  CAS  PubMed  Google Scholar 

  105. Bi, K., Zhang, X., Chen, W., & Diao, H. (2020). MicroRNAs Regulate intestinal immunity and gut microbiota for gastrointestinal health: A comprehensive review. Genes, 11(9), 1075.

    Article  CAS  PubMed Central  Google Scholar 

  106. Kim, J. Y., Lee, J.-S., Han, Y.-S., Lee, J. H., Bae, I., Yoon, Y. M., Kwon, S. M., & Lee, S. H. (2015). Pretreatment with lycopene attenuates oxidative stress-induced apoptosis in human mesenchymal stem cells. Biomolecules & Therapeutics, 23(6), 517.

    Article  CAS  Google Scholar 

  107. Yucel, Y., Tabur, S., Gozeneli, O., Kocarslan, S., Seker, A., Buyukaslan, H., Şavik, E., Aktumen, A., Ozgonul, A., & Uzunkoy, A. (2016). The effects of lycopene on intestinal injury due to methotrexate in rats. Redox Report, 21(3), 113–118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Bestwick, C. S., & Milne, L. (2000). Effects of β-carotene on antioxidant enzyme activity, intracellular reactive oxygen and membrane integrity within post confluent Caco-2 intestinal cells. Biochimica et Biophysica Acta (BBA)-General Subjects, 1474(1), 47–55.

    Article  CAS  Google Scholar 

  109. Padmanabhan, S., Waly, M. I., Taranikanti, V., Guizani, N., Ali, A., Rahman, M. S., Al-Attabi, Z., Al-Malky, R. N., Al-Maskari, S. N. M., Al-Ruqaishi, B. R. S., Dong, J., & Deth, R. C. (2019). Folate/Vitamin B12 supplementation combats oxidative stress-associated carcinogenesis in a rat model of colon cancer. Nutrition and Cancer, 71(1), 100–110.

  110. Van De Lagemaat, E. E., De Groot, L. C. P. G. M., & Van Den Heuvel, E. G. H. M. (2019). Vitamin B12 in relation to oxidative stress: a systematic review. Nutrients, 11(2), 482.

    Article  PubMed Central  CAS  Google Scholar 

  111. Pehlivan, F. E. (2017). Vitamin C: An antioxidant agent. Vitamin C, 2, 23–35.

    Google Scholar 

  112. Traber, M. G., Buettner, G. R., & Bruno, R. S. (2019). The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome. Redox biology, 21, 101091.

    Article  CAS  PubMed  Google Scholar 

  113. Miyazawa, T., Burdeos, G. C., Itaya, M., Nakagawa, K., & Miyazawa, T. (2019). Vitamin E: Regulatory redox interactions. IUBMB Life, 71(4), 430–441.

    Article  CAS  PubMed  Google Scholar 

  114. Berridge, M. J. (2016). Vitamin D, reactive oxygen species and calcium signalling in ageing and disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 371(1700), 20150434.

    Article  CAS  Google Scholar 

  115. Lu, R., Zhang, Y. G., Xia, Y., & Sun, J. (2019). Imbalance of autophagy and apoptosis in intestinal epithelium lacking the vitamin D receptor. The FASEB Journal, 33(11), 11845–11856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zheng, P., Song, Y., Tian, Y., Zhang, H., Yu, B., He, J., Mao, X., Yu, J., Luo, Y., & Luo, J. (2018). Dietary arginine supplementation affects intestinal function by enhancing antioxidant capacity of a nitric oxide–independent pathway in low-birth-weight piglets. The Journal of Nutrition, 148(11), 1751–1759.

    Article  PubMed  PubMed Central  Google Scholar 

  117. He, L., Long, J., Zhou, X., Liu, Y., Li, T., & Wu, X. (2020). Serine is required for the maintenance of redox balance and proliferation in the intestine under oxidative stress. The FASEB Journal, 34(3), 4702–4717.

    Article  CAS  PubMed  Google Scholar 

  118. Cao, S., Wang, C., Yan, J., Li, X., Wen, J., & Hu, C. (2020). Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway. Free Radical Biology and Medicine, 147, 8–22.

    Article  CAS  PubMed  Google Scholar 

  119. Yucel, A. F., Kanter, M., Pergel, A., Erboga, M., & Guzel, A. (2011). The role of curcumin on intestinal oxidative stress, cell proliferation and apoptosis after ischemia/reperfusion injury in rats. Journal of Molecular Histology, 42(6), 579.

    Article  CAS  PubMed  Google Scholar 

  120. Xue, Y., Teng, Y., Chen, M., Li, Z., & Wang, G. (2021). Antioxidant activity and mechanism of avenanthramides: Double H+/e–processes and role of the catechol, guaiacyl, and carboxyl groups. Journal of Agricultural and Food Chemistry, 69, 7178–7189.

    Article  CAS  PubMed  Google Scholar 

  121. Zhang, Y., Ni, T., Zhang, D., Liu, H., Wang, J., & Sun, B. (2020). Consumption of avenanthramides extracted from oats reduces weight gain, oxidative stress, inflammation and regulates intestinal microflora in high fat diet-induced mice. Journal of Functional Foods, 65, 103774.

    Article  CAS  Google Scholar 

  122. Forester, S. C., & Lambert, J. D. (2011). The role of antioxidant versus pro-oxidant effects of green tea polyphenols in cancer prevention. Molecular Nutrition & Food Research, 55(6), 844–854.

    Article  CAS  Google Scholar 

  123. Wang, Y., Wu, Y., Wang, Y., Xu, H., Mei, X., Yu, D., Wang, Y., & Li, W. (2017). Antioxidant properties of probiotic bacteria. Nutrients, 9(5), 521.

    Article  PubMed Central  CAS  Google Scholar 

  124. Ballway, J. W., & Song, B.-J. (2021). Translational approaches with antioxidant phytochemicals against alcohol-mediated oxidative stress, gut dysbiosis, intestinal barrier dysfunction and fatty liver disease. Antioxidants, 10(3), 384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kim, S.-M., Hwang, K.-A., Choi, D.-W., & Choi, K.-C. (2018). The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells. Food and Chemical Toxicology, 121, 657–665.

    Article  CAS  PubMed  Google Scholar 

  126. Morsch, A. C., Wisniewski, E., Luciano, T. F., Comin, V., de BemSilveira, G., de Oliveira Marques, S., Thirupathi, A., Silveira Lock, P. C., & De Souza, C. T. (2019). Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice. Redox Report, 24(1), 27–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Balali-M, M., Naseri, K., Tahergorabi, Z., Khazdair, M. R., & Sadeghi, M. (2021). Toxic mechanisms of five heavy metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. Frontiers in Pharmacology, 12, 643972.

    Article  CAS  Google Scholar 

  128. Sahuri-A, M., Mould, R. R., Shinjyo, N., Bligh, S., Nunn, A. V., Guy, G. W., Thomas, E. L., & Bell, J. D. (2021). Acetate induces growth arrest in colon cancer cells through modulation of mitochondrial function. Frontiers in Nutrition, 8, 150.

    Google Scholar 

  129. Liu, P., Wang, Y., Yang, G., Zhang, Q., Meng, L., Xin, Y., & Jiang, X. (2021). The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacological Research, 165, 105420.

    Article  CAS  PubMed  Google Scholar 

  130. Salahshouri, P., Emadi-Baygi, M., Jalili, M., Khan, F. M., Wolkenhauer, O., & Salehzadeh-Y, A. (2021). A metabolic model of intestinal secretions: The link between human microbiota and colorectal cancer progression. Metabolites, 11(7), 456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Albracht-Schulte, K., Islam, T., Johnson, P., & Moustaid-Moussa, N. (2021). Systematic review of beef protein effects on gut microbiota: Implications for health. Advances in Nutrition, 12(1), 102–114.

    Article  PubMed  Google Scholar 

  132. Portincasa, P., Di Ciaula, A., Garruti, G., Vacca, M., De Angelis, M., & Wang, D.Q.-H. (2020). Bile acids and GPBAR-1: Dynamic interaction involving genes, environment and gut microbiome. Nutrients, 12(12), 3709.

    Article  CAS  PubMed Central  Google Scholar 

  133. Lee, K.-A., Kim, B., You, H., & Lee, W.-J. (2015). Uracil-induced signaling pathways for DUOX-dependent gut immunity. Fly, 9(3), 115–120.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Lee, K.-A., Kim, B., Bhin, J., Kim, D. H., You, H., Kim, E.-K., Kim, S.-H., Ryu, J.-H., Hwang, D., & Lee, W.-J. (2015). Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes. Cell Host & Microbe, 17(2), 191–204.

    Article  CAS  Google Scholar 

  135. Pani, B., & Singh, B. B. (2009). Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium, 45(6), 625–633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Iftekhar, A., & Sigal, M. (2021). Defence and adaptation mechanisms of the intestinal epithelium upon infection. International Journal of Medical Microbiology, 311(3), 151486.

    Article  CAS  PubMed  Google Scholar 

  137. Litvak, Y., Byndloss, M. X., & Bäumler, A. J. (2018). Colonocyte metabolism shapes the gut microbiota. Science, 362(6418), 9076.

  138. Lopez, C. A., Miller, B. M., Rivera-Chávez, F., Velazquez, E. M., Byndloss, M. X., Chávez-Arroyo, A., Lokken, K. L., Tsolis, R. M., Winter, S. E., & Bäumler, A. J. (2016). Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration. Science, 353(6305), 1249–1253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Winter, S. E., Thiennimitr, P., Winter, M. G., Butler, B. P., Huseby, D. L., Crawford, R. W., Russell, J. M., Bevins, C. L., Adams, L. G., & Tsolis, R. M. (2010). Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature, 467(7314), 426–429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Lu, X., Li, C., Li, C., Li, P., Fu, E., Xie, Y., & Jin, F. (2017). Heat-labile enterotoxin-induced PERK-CHOP pathway activation causes intestinal epithelial cell apoptosis. Frontiers in Cellular and Infection Microbiology, 7, 244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Anes, J., Dever, K., Eshwar, A., Nguyen, S., Cao, Y., Sivasankaran, S. K., Sakalauskaitė, S., Lehner, A., Devineau, S., & Daugelavičius, R. (2021). Analysis of the oxidative stress regulon identifies soxS as a genetic target for resistance reversal in multidrug-resistant Klebsiella pneumoniae. MBio, 12(3), e00867-e921.

    Article  CAS  PubMed Central  Google Scholar 

  142. Dong, T. G., Dong, S., Catalano, C., Moore, R., Liang, X., & Mekalanos, J. J. (2015). Generation of reactive oxygen species by lethal attacks from competing microbes. Proceedings of the National Academy of Sciences, 112(7), 2181–2186.

    Article  CAS  Google Scholar 

  143. Wang, P., Zhang, H., Liu, Y., Lv, R., Liu, X., Song, X., Wang, J., & Jiang, L. (2020). SoxS is a positive regulator of key pathogenesis genes and promotes intracellular replication and virulence of Salmonella Typhimurium. Microbial Pathogenesis, 139, 103925.

    Article  CAS  PubMed  Google Scholar 

  144. Das, K., Garnica, O., & Dhandayuthapani, S. (2016). Modulation of host miRNAs by intracellular bacterial pathogens. Frontiers in Cellular and Infection Microbiology, 6, 79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Hansson, G. C. (2012). Role of mucus layers in gut infection and inflammation. Current Opinion in Microbiology, 15(1), 57–62.

    Article  CAS  PubMed  Google Scholar 

  146. Glover, L. E., Lee, J. S., & Colgan, S. P. (2016). Oxygen metabolism and barrier regulation in the intestinal mucosa. The Journal of Clinical Investigation, 126(10), 3680–3688.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Campbell, E. L., & Colgan, S. P. (2015). Neutrophils and inflammatory metabolism in antimicrobial functions of the mucosa. Journal of Leukocyte Biology, 98(4), 517–522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Colgan, S. P., & Campbell, E. L. (2017). Oxygen metabolism and innate immune responses in the gut. Journal of Applied Physiology (Bethesda, Md. : 1985), 123(5), 1321–1327.

    Article  CAS  Google Scholar 

  149. Ruder, B., & Becker, C. (2020). At the forefront of the mucosal barrier: The role of macrophages in the intestine. Cells, 9(10), 2162.

    Article  CAS  PubMed Central  Google Scholar 

  150. Murai, M., Turovskaya, O., Kim, G., Madan, R., Karp, C. L., Cheroutre, H., & Kronenberg, M. (2009). Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nature Immunology, 10(11), 1178–1184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Smythies, L. E., Sellers, M., Clements, R. H., Mosteller-Barnum, M., Meng, G., Benjamin, W. H., Orenstein, J. M., & Smith, P. D. (2005). Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. The Journal of Clinical Investigation, 115(1), 66–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Arango Duque, G., & Descoteaux, A. (2014). Macrophage cytokines: Involvement in immunity and infectious diseases. Frontiers in Immunology, 5, 491.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014). Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling, 20(7), 1126–1167.

    Article  CAS  Google Scholar 

  154. Yarosz, E. L., & Chang, C.-H. (2018). The role of reactive oxygen species in regulating T cell-mediated immunity and disease. Immune Network, 18(1), e14.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Fisher-Wellman, K. H., Gilliam, L. A., Lin, C.-T., Cathey, B. L., Lark, D. S., & Neufer, P. D. (2013). Mitochondrial glutathione depletion reveals a novel role for the pyruvate dehydrogenase complex as a key H2O2-emitting source under conditions of nutrient overload. Free Radical Biology and Medicine, 65, 1201–1208.

    Article  CAS  PubMed  Google Scholar 

  156. Starkov, A. A., Fiskum, G., Chinopoulos, C., Lorenzo, B. J., Browne, S. E., Patel, M. S., & Beal, M. F. (2004). Mitochondrial α-ketoglutarate dehydrogenase complex generates reactive oxygen species. Journal of Neuroscience, 24(36), 7779–7788.

    Article  CAS  PubMed  Google Scholar 

  157. Waring, P., & Müllbacher, A. (1999). Cell death induced by the Fas/Fas ligand pathway and its role in pathology. Immunology and Cell Biology, 77(4), 312–317.

    Article  CAS  PubMed  Google Scholar 

  158. Bennett, S. J., Griffiths, H. R. (2013). Regulation of T-Cell functions by oxidative stress. In: Alcaraz, M., Gualillo, O., Sánchez-Pernaute, O. (eds) Studies on arthritis and joint disorders. Oxidative stress in applied basic research and clinical practice (pp. 33–48). Humana Press

  159. Biton, M., Haber, A. L., Rogel, N., Burgin, G., Beyaz, S., Schnell, A., Ashenberg, O., Su, C.-W., Smillie, C., & Shekhar, K. (2018). T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell, 175(5), 1307-1320. e22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Haber, A. L., Biton, M., Rogel, N., Herbst, R. H., Shekhar, K., Smillie, C., Burgin, G., Delorey, T. M., Howitt, M. R., & Katz, Y. (2017). A single-cell survey of the small intestinal epithelium. Nature, 551(7680), 333–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Vijay, K. (2018). Toll-like receptors in immunity and inflammatory diseases: Past, present, and future. International Immunopharmacology, 59, 391–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Li, P., & Chang, M. (2021). Roles of PRR-mediated signaling pathways in the regulation of oxidative stress and inflammatory diseases. International Journal of Molecular Sciences, 22(14), 7688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Nguyen, P. L., Bui, B. P., Lee, H., & Cho, J. (2021). A Novel 1, 8-Naphthyridine-2-carboxamide derivative attenuates inflammatory responses and cell migration in LPS-treated BV2 cells via the suppression of ROS generation and TLR4/Myd88/NF-κB signaling pathway. International Journal of Molecular Sciences, 22(5), 2527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Brandt, S. L., & Serezani, C. H. (2017). Too much of a good thing: How modulating LTB4 actions restore host defense in homeostasis or disease. Semin Immunol, 33, 37–43.

  165. Meng, F. W., & Biteau, B. (2015). A Sox transcription factor is a critical regulator of adult stem cell proliferation in the Drosophila intestine. Cell Reports, 13(5), 906–914.

    Article  CAS  PubMed  Google Scholar 

  166. Kohchi, C., Inagawa, H., Nishizawa, T., & Soma, G.-I. (2009). ROS and Innate. Immunity, 29(3), 817–821.

    CAS  Google Scholar 

  167. Neal, M. D., Sodhi, C. P., Jia, H., Dyer, M., Egan, C. E., Yazji, I., Good, M., Afrazi, A., Marino, R., Slagle, D., Ma, C., Branca, M. F., Prindle, T., Jr., Grant, Z., Ozolek, J., & Hackam, D. J. (2012). Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. Journal of Biological Chemistry, 287(44), 37296–37308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Shekhova, E. (2020). Mitochondrial reactive oxygen species as major effectors of antimicrobial immunity. PLoS Pathogens, 16(5), e1008470–e1008470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Eltzschig, H. K., Eckle, T., Mager, A., Küper, N., Karcher, C., Weissmüller, T., Boengler, K., Schulz, R., Robson, S. C., & Colgan, S. P. (2006). ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circulation Research, 99(10), 1100–1108.

    Article  CAS  PubMed  Google Scholar 

  170. Linden, J. (2001). Molecular approach to adenosine receptors: Receptor-mediated mechanisms of tissue protection. Annual Review of Pharmacology and Toxicology, 41(1), 775–787.

    Article  CAS  PubMed  Google Scholar 

  171. Alam, A., Leoni, G., Quiros, M., Wu, H., Desai, C., Nishio, H., Jones, R. M., Nusrat, A., & Neish, A. S. (2016). The microenvironment of injured murine gut elicits a local pro-restitutive microbiota. Nature Microbiology, 1(2), 1–8.

    Article  CAS  Google Scholar 

  172. Hageman, J. H., Heinz, M. C., Kretzschmar, K., van der Vaart, J., Clevers, H., & Snippert, H. J. (2020). Intestinal regeneration: Regulation by the microenvironment. Developmental Cell, 54(4), 435–446.

    Article  CAS  PubMed  Google Scholar 

  173. Quiros, M., Nishio, H., Neumann, P. A., Siuda, D., Brazil, J. C., Azcutia, V., Hilgarth, R., O’Leary, M. N., Garcia-Hernandez, V., & Leoni, G. (2017). Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling. The Journal of Clinical Investigation, 127(9), 3510–3520.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Caprara, G., Allavena, P., & Erreni, M. (2020). Intestinal macrophages at the crossroad between diet, inflammation, and cancer. International Journal of Molecular Sciences, 21(14), 4825.

    Article  CAS  PubMed Central  Google Scholar 

  175. Mola, S., Pandolfo, C., Sica, A., & Porta, C. (2020). The Macrophages-Microbiota interplay in Colorectal Cancer (CRC)-Related inflammation: Prognostic and therapeutic significance. International Journal of Molecular Sciences, 21(18), 6866.

    Article  CAS  PubMed Central  Google Scholar 

  176. Na, Y. R., Stakenborg, M., Seok, S. H., & Matteoli, G. (2019). Macrophages in intestinal inflammation and resolution: A potential therapeutic target in IBD. Nature Reviews Gastroenterology & Hepatology, 16(9), 531–543.

    Article  CAS  Google Scholar 

  177. Segrist, E., & Cherry, S. (2020). Using diverse model systems to define intestinal epithelial defenses to enteric viral infections. Cell Host & Microbe, 27(3), 329–344.

    Article  CAS  Google Scholar 

  178. Wang, Y., Chen, Y., Zhang, X., Lu, Y., & Chen, H. (2020). New insights in intestinal oxidative stress damage and the health intervention effects of nutrients: A review. Journal of Functional Foods, 75, 104248.

    Article  CAS  Google Scholar 

  179. Alonso, S., & Yilmaz, Ö. H. (2018). Nutritional regulation of intestinal stem cells. Annual Review of Nutrition, 38, 273–301.

    Article  CAS  PubMed  Google Scholar 

  180. Bonfini, A., Dobson, A. J., Duneau, D., Revah, J., Liu, X., Houtz, P., & Buchon, N. (2021). Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size. ELife, 10, e64125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Puertollano, M. A., Puertollano, E., Alvarez de Cienfuegos, G., & de Pablo, M. A. (2011). Dietary antioxidants: immunity and host defense. Current Topics in Medicinal Chemistry, 11(14), 1752–1766.

    Article  CAS  PubMed  Google Scholar 

  182. Singh, R. K., Chang, H.-W., Yan, D., Lee, K. M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., & Zhu, T. H. (2017). Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine, 15(1), 1–17.

    Article  CAS  Google Scholar 

  183. Wilhelmi de Toledo, F., Grundler, F., Goutzourelas, N., Tekos, F., Vassi, E., Mesnage, R., & Kouretas, D. (2020). Influence of long-term fasting on blood redox status in humans. Antioxidants, 9(6), 496.

    Article  PubMed Central  CAS  Google Scholar 

  184. Tosar, J. P., Rovira, C., Naya, H., & Cayota, A. (2014). Mining of public sequencing databases supports a non-dietary origin for putative foreign miRNAs: Underestimated effects of contamination in NGS. RNA, 20(6), 754–757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Mu, J., Zhuang, X., Wang, Q., Jiang, H., Deng, Z. B., Wang, B., Zhang, L., Kakar, S., Jun, Y., & Miller, D. (2014). Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Molecular Nutrition & Food Research, 58(7), 1561–1573.

    Article  CAS  Google Scholar 

  186. Teng, Y., Ren, Y., Sayed, M., Hu, X., Lei, C., Kumar, A., Hutchins, E., Mu, J., Deng, Z., & Luo, C. (2018). Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host & Microbe, 24(5), 637-652. e8.

    Article  CAS  Google Scholar 

  187. Manca, S., Upadhyaya, B., Mutai, E., Desaulniers, A. T., Cederberg, R. A., White, B. R., & Zempleni, J. (2018). Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns. Scientific Reports, 8(1), 1–11.

    Article  CAS  Google Scholar 

  188. Jones, D. P. (2006). Redefining oxidative stress. Antioxidants & Redox Signaling, 8(9–10), 1865–1879.

    Article  CAS  Google Scholar 

  189. Ma, Q. (2013). Role of nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology, 53, 401–426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Kalinga Institute of Industrial Technology (KIIT), deemed to be University, Bhubaneswar, Odisha, 751024, India

    Arijit Nath

  2. Haldia Institute of Technology (HIT), Haldia, West Bengal, 721657, India

    Pitam Chakrabarti & Sushmita Sen

  3. Centre for Healthcare Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur, India

    Ananya Barui

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  1. Arijit Nath
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  2. Pitam Chakrabarti
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  3. Sushmita Sen
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  4. Ananya Barui
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AN wrote the original draft of the manuscript under the guidance of AB. AB, AN, and PC reviewed and edited the draft. PC and SS worked on illustrations.

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Correspondence to Ananya Barui.

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Nath, A., Chakrabarti, P., Sen, S. et al. Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function. Stem Cell Rev and Rep 18, 2328–2350 (2022). https://doi.org/10.1007/s12015-022-10377-1

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