Revisiting the starved gut hypothesis in inflammatory bowel disease-Immunometabolism-CSCIED科技核心评价数据库-手机版

Revisiting the starved gut hypothesis in inflammatory bowel disease

Revisiting the starved gut hypothesis in inflammatory bowel disease

ES评分 0 浏览量：1008 下载量：0

DOI	10.1097/IN9.0000000000000016
刊名	Immunometabolism IJ
年，卷(期)	2023, 5(1)
作者	Colgan, Sean P.; Wang, Ruth X.; Hall, Caroline H. T.; Bhagavatula, Geetha; Lee, J. Scott,
作者单位	[Colgan, Sean P.; Wang, Ruth X.; Hall, Caroline H. T.; Bhagavatula, Geetha; Lee, J. Scott] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA; [Colgan, Sean P.; Lee, J. Scott] Univ Colorado, Sc
摘要	Active episodes of inflammatory bowel disease (IBD), which include ulcerative colitis and Crohn's disease, coincide with profound shifts in the composition of the microbiota and host metabolic energy demand. Intestinal epithelial cells (IEC) that line the small intestine and colon serve as an initial point for contact for the microbiota and play a central role in innate immunity. In the 1980s, Roediger et al proposed the hypothesis that IBD represented a disease of diminished mucosal nutrition and energy deficiency (starved gut) that strongly coincided with the degree of inflammation. These studies informed the scientific community about the important contribution of microbial-derived metabolites, particularly short-chain fatty acids (SCFA) such as butyrate, to overall energy homeostasis. Decades later, it is appreciated that disease-associated shifts in the microbiota, termed dysbiosis, places inordinate demands on energy acquisition within the mucosa, particularly during active inflammation. Here, we review the topic of tissue energetics in mucosal health and disease from the original perspective of that proposed by the starved gut hypothesis.
Abstract	Active episodes of inflammatory bowel disease (IBD), which include ulcerative colitis and Crohn's disease, coincide with profound shifts in the composition of the microbiota and host metabolic energy demand. Intestinal epithelial cells (IEC) that line the small intestine and colon serve as an initial point for contact for the microbiota and play a central role in innate immunity. In the 1980s, Roediger et al proposed the hypothesis that IBD represented a disease of diminished mucosal nutrition and energy deficiency (starved gut) that strongly coincided with the degree of inflammation. These studies informed the scientific community about the important contribution of microbial-derived metabolites, particularly short-chain fatty acids (SCFA) such as butyrate, to overall energy homeostasis. Decades later, it is appreciated that disease-associated shifts in the microbiota, termed dysbiosis, places inordinate demands on energy acquisition within the mucosa, particularly during active inflammation. Here, we review the topic of tissue energetics in mucosal health and disease from the original perspective of that proposed by the starved gut hypothesis.
关键词	metabolism; microbiota; inflammation; creatine; butyrate; innate immunity colitis; epithelium
KeyWord	metabolism; microbiota; inflammation; creatine; butyrate; innate immunity colitis; epithelium
基金项目
页码	1-6

参考文献
相关文献

[1]. Dahlhamer JZ, Ward BW, Wheaton AG, et al. Prevalence of inflammatory bowel disease among adults aged >18 years - United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65:1166–9.

[2]. M’Koma AE. Inflammatory bowel disease: an expanding global health problem. Clin Med Insights Gastroenterol. 2013;6:33–47.

[3]. Lee SH, Kwon JE, Cho M-L. Immunological pathogenesis of inflammatory bowel disease. Intestinal Res. 2018;16(1):26–42.

[4]. Glover LE, Colgan SP. Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. Gastroenterology. 2011;140(6):1748–55.

[5]. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24. doi: 10.1038/nature11582.

[6]. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164(3):337–40.

[7]. Colgan SP, Campbell EL, Kominsky DJ. Hypoxia and mucosal inflammation. Ann Rev Pathol. 2016;11:77–100.

[8]. Glover LE, Lee JS, Colgan SP. Oxygen metabolism and barrier regulation in the intestinal mucosa. J Clin Invest. 2016;126(10):3680–8.

[9]. Taylor CT, Colgan SP. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol. 2017;17(12):774–85.

[10]. Roediger WE. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980;21(9):793–8. doi: 10.1136/gut.21.9.793.

[11]. Roediger WE. Bacterial short-chain fatty acids and mucosal diseases of the colon. Br J Surg. 1988;75(4):346–8.

[12]. Roediger WE. The starved colon-diminished mucosal nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33(10):858–62.

[13]. Roediger WE. Colonic epithelial metabolism in ulcerative colitis. Gut. 1993;34(11):1646.

[14]. Roediger WE, Heyworth M, Willoughby P, et al. Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis. J Clin Pathol. 1982;35(3):323–6.

[15]. Roediger WE, Nance S. Selective reduction of fatty acid oxidation in colonocytes: correlation with ulcerative colitis. Lipids. 1990;25(10):646–52.

[16]. Roediger WEW. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980;316(8197):712–5. doi: 10.1016/s0140-6736(80)91934-0.

[17]. Carra GE, Ibanez JE, Saravi FD. Electrogenic transport, oxygen consumption, and sensitivity to acute hypoxia of human colonic epithelium. Int J Colorectal Dis. 2011;26(9):1205–10.

[18]. Del Castillo JR, Ricabarra B, Sulbaran-Carrasco MC. Intermediary metabolism and its relationship with ion transport in isolated guinea pig colonic epithelial cells. Am J Physiol. 1991;260(3 Pt 1):C626–34.

[19]. Kelly CJ, Zheng L, Campbell EL, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17(5):662–71.

[20]. Marin-Hernandez A, Gallardo-Perez JC, Ralph SJ, et al. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 2009;9(9):1084–101.

[21]. De Miguel MP, Alcaina Y, de la Maza DS, et al. Cell metabolism under microenvironmental low oxygen tension levels in stemness, proliferation and pluripotency. Curr Mol Med. 2015;15(4):343–59.

[22]. Kekuda R, Manoharan P, Baseler W, et al. Monocarboxylate 4 mediated butyrate transport in a rat intestinal epithelial cell line. Dig Dis Sci. 2013;58(3):660–7. doi: 10.1007/s10620-012-2407-x.

[23]. Ullah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem. 2006;281(14):9030–7. doi: 10.1074/jbc.M511397200.

[24]. Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3(3):177–85. doi: 10.1016/j.cmet.2006.02.002.

[25]. Blouin JM, Penot G, Collinet M, et al. Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. Int J Cancer. 2011;128(11):2591–601. doi: 10.1002/ijc.25599.

[26]. Smith SA, Ogawa SA, Chau L, et al. Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines. J Clin Invest. 2021;131(1):e133371. doi: 10.1172/JCI133371.

[27]. Sivaprakasam S, Bhutia YD, Yang S, et al. Short-chain fatty acid transporters: role in colonic homeostasis. Compr Physiol. 2017;8(1):299–314. doi: 10.1002/cphy.c170014.

[28]. Thibault R, De Coppet P, Daly K, et al. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007;133(6):1916–27.

[29]. Villodre Tudela C, Boudry C, Stumpff F, et al. Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling. Br J Nutr. 2015;113(4):610–7.

[30]. Cuff MA, Lambert DW, Shirazi‐Beechey SP. Substrateinduced regulation of the human colonic monocarboxylate transporter, MCT1. J Physiol. 2002;539(2):361–71.

[31]. Davie JR. Inhibition of histone deacetylase activity by butyrate. J Nutr. 2003;133(7 Suppl):2485S–93S.

[32]. Steliou K, Boosalis MS, Perrine SP, et al. Butyrate histone deacetylase inhibitors. Biores Open Access. 2012;1(4):192–8.

[33]. Wang RX, Henen MA, Lee JS, et al. Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. Gut Microbes. 2021;13(1):1938380.

[34]. Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40(1):128–39.

[35]. McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients. 2017;9(12):1348.

[36]. Hosseinkhani F, Heinken A, Thiele I, et al. The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases. Gut Microbes. 2021;13(1):1–22.

[37]. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–50.

[38]. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–73.

[39]. Wen S, He L, Zhong Z, et al. Stigmasterol restores the balance of Treg/Th17 cells by activating the Butyrate-PPARgamma axis in colitis. Front Immunol. 2021;12:741934.

[40]. Zhang M, Zhou Q, Dorfman RG, et al. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats. BMC Gastroenterol. 2016;16(1):84.

[41]. Wang RX, Lee JS, Campbell EL, et al. Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin. Proc Natl Acad Sci USA. 2020;117(21):11648–57.

[42]. Mundel P, Heid HW, Mundel TM, et al. an actin-associated protein in telencephalic dendrites and renal podocytes. J Cell Biol. 1997;139(1):193–204.

[43]. Mundel P, Gilbert P, Kriz W. Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein. J Histochem Cytochem. 1991;39(8):1047–56.

[44]. Kannan N, Tang VW. Synaptopodin couples epithelial contractility to alpha-actinin-4-dependent junction maturation. J Cell Biol. 2015;211(2):407–34.

[45]. Mun GI, Park S, Kremerskothen J, et al. Expression of synaptopodin in endothelial cells exposed to laminar shear stress and its role in endothelial wound healing. FEBS Lett. 2014;588(6):1024–30.

[46]. Chalovich JM, Schroeter MM. Synaptopodin family of natively unfolded, actin binding proteins: physical properties and potential biological functions. Biophys Rev. 2010;2(4):181–9.

[47]. McCall W, Persky AM. Pharmacokinetics of creatine. Subcell Biochem. 2007;46:261–73.

[48]. Kitzenberg D, Colgan SP, Glover LE. Creatine kinase in ischemic and inflammatory disorders. Clin Transl Med. 2016;5(1):31.

[49]. Streijger F, Oerlemans F, Ellenbroek BA, et al. Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behav Brain Res. 2005;157(2):219–34. doi: 10.1016/j.bbr.2004.07.002.

[50]. Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40(5):1271–96.

[51]. Wallimann T, Wyss M, Brdiczka D, et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the “phosphocreatine circuit” for cellular energy homeostasis. Biochem J. 1992;281(pt 1)(pt 1):21–40. doi: 10.1042/bj2810021.

[52]. Wallimann T, Hemmer W. Creatine kinase in non-muscle tissues and cells. Mol Cell Biochem. 1994;133-134:193–220.

[53]. Peral MJ, Garcia-Delgado M, Calonge ML, et al. Human, rat and chicken small intestinal Na+ - Cl- -creatine transporter: functional, molecular characterization and localization. J Physiol. 2002;545(1):133–44.

[54]. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107–213.

[55]. Okumu DO, Aponte-Collazo LJ, Dewar BJ, et al. Lyn regulates creatine uptake in an imatinib-resistant CML cell line. Biochim Biophys Acta Gen Subj. 2020;1864(4):129507.

[56]. Glover LE, Bowers BE, Saeedi B, et al. Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis. Proc Natl Acad Sci USA. 2013;110(49):19820–5.

[57]. Lee JS, Wang RX, Alexeev EE, et al. Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function. J Biol Chem. 2018;293(16):6039–51.

[58]. Dawiskiba T, Deja S, Mulak A, et al. Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases. World J Gastroenterol. 2014;20(1):163–74.

[59]. Notararigo S, Martin-Pastor M, Vinuela-Roldan JE, et al. Targeted (1)H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF. J Mol Med (Berl). 2021;99(9):1251–64.

[60]. Sutter M, Hruz P, Niess JH. High serum creatine kinase levels in infliximab and vedolizumab-treated inflammatory bowel disease patients. Inflamm Intest Dis. 2021;6(3):165–74.

[61]. Sandborn WJ, Ghosh S, Panes J, et al. Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis. Gastroenterology. 2020;158(8):2139–49.e14.

[62]. D’Haens G, Panes J, Louis E, et al. Upadacitinib was efficacious and well-tolerated over 30 months in patients with crohn’s disease in the CELEST extension study. Clin Gastroenterol Hepatol. 2022;20(10):2337–46.e3. doi: 10.1016/j.cgh.2021.12.030.

[63]. Starr AE, Deeke SA, Ning Z, et al. Associations between cellular energy and pediatric inflammatory bowel disease patient response to treatment. J Proteome Res. 2021;20(9):4393–404.

[64]. Hall CHT, Lee JS, Murphy EM, et al. Creatine transporter, reduced in colon tissues from patients with inflammatory bowel diseases, regulates energy balance in intestinal epithelial cells, epithelial integrity, and barrier function. Gastroenterology. 2020;159(3):984–998.e1.

[65]. Turer E, McAlpine W, Wang KW, et al. Creatine maintains intestinal homeostasis and protects against colitis. Proc Natl Acad Sci USA. 2017;114(7):E1273–81.

[66]. Wallimann T, Hall CHT, Colgan SP, et al. Creatine supplementation for patients with inflammatory bowel diseases: a scientific rationale for a clinical trial. Nutrients. 2021;13(5):1429.

[67]. Mackinnon AM, Deller DJ. Purine nucleotide biosynthesis in gastrointestinal mucosa. Biochimica et Biophysica Acta (BBA)-Nucleic Acids Protein Synthesis. 1973;319(1):1–4.

[68]. Savaiano DA, Clifford AJ. Adenine, the precursor of nucleic acids in intestinal cells unable to synthesize purines de novo. J Nutr. 1981;111(10):1816–22.

[69]. Grimble GK. Dietary nucleotides and gut mucosal defence. Gut. 1994;35(1 Suppl):S46–51.

[70]. Lee JS, Wang RX, Goldberg MS, et al. Microbiota-sourced purines support wound healing and mucus barrier function. iScience. 2020:101226. doi: 10.1016/j.isci.2020.101226.

[71]. Paramsothy S, Nielsen S, Kamm MA, et al. Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis. Gastroenterology. 2019;156(5):1440–54.e2.

[72]. Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017;312(1):G52–62.

[73]. Mars RAT, Yang Y, Ward T, et al. Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell. 2020;183(4):1137–40.

[74]. Zeng MY, Inohara N, Nunez G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunol. 2017;10(1):18–26.

[75]. Shaw KA, Bertha M, Hofmekler T, et al. Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. Genome Med. 2016;8(1):75.

[76]. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.

[77]. Ott SJ, Waetzig GH, Rehman A, et al. Efficacy of sterile fecal filtrate transfer for treating patients with clostridium difficile infection. Gastroenterology. 2017;152(4):799–811.e7.

引用本文

Colgan, Sean P.; Wang, Ruth X.; Hall, Caroline H. T.; Bhagavatula, Geetha; Lee, J. Scott. Revisiting the starved gut hypothesis in inflammatory bowel disease [J]. Immunometabolism. 2023; 5; (1). 1 - 6.

文献评论

相关学者

相关机构