{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T20:31:27Z","timestamp":1776803487016,"version":"3.51.2"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Key Research, and Development Project of Zhejiang Province","award":["2021C03064"],"award-info":[{"award-number":["2021C03064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL\/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.<\/jats:p>","DOI":"10.3390\/nu15051155","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T01:59:10Z","timestamp":1677463150000},"page":"1155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Chenmin","family":"Hu","sequence":"first","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"},{"name":"Department of Pediatrics, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenxi","family":"Yan","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enfu","family":"Tao","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-5540","authenticated-orcid":false,"given":"Zhenya","family":"Zhu","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Chen","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-4347","authenticated-orcid":false,"given":"Marong","family":"Fang","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China"},{"name":"Institute of System Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4829-2041","authenticated-orcid":false,"given":"Mizu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Gastrointestinal Laboratory, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"},{"name":"Department of Gastroenterology, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/S0140-6736(20)31548-8","article-title":"Irritable bowel syndrome","volume":"396","author":"Ford","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.14309\/ajg.0000000000001036","article-title":"ACG Clinical guideline: Management of irritable bowel syndrome","volume":"116","author":"Lacy","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1053\/j.gastro.2019.12.021","article-title":"Prevalence of Rome IV functional bowel disorders among adults in the United States, Canada, and the United Kingdom","volume":"158","author":"Palsson","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S2468-1253(20)30217-X","article-title":"Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: A systematic review and meta-analysis","volume":"5","author":"Oka","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/jama.2020.22532","article-title":"Diagnosis and treatment of irritable bowel syndrome: A review","volume":"325","author":"Camilleri","year":"2021","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The microbiota-gut-brain axis: From motility to mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.gtc.2021.03.006","article-title":"Behavioral strategies for irritable bowel syndrome: Brain-gut or gut-brain?","volume":"50","author":"Jagielski","year":"2021","journal-title":"Gastroenterol. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1053\/j.gastro.2020.02.022","article-title":"Prostaglandin E2, produced by mast cells in colon tissues from patients with irritable bowel syndrome, contributes to visceral hypersensitivity in mice","volume":"158","author":"Grabauskas","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.5009\/gnl210208","article-title":"Postinfection irritable bowel syndrome","volume":"16","author":"Ghoshal","year":"2022","journal-title":"Gut Liver"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ivashkin, V., Poluektov, Y., Kogan, E., Shifrin, O., Sheptulin, A., Kovaleva, A., Kurbatova, A., Krasnov, G., and Poluektova, E. (2021). Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252930"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101602","DOI":"10.1016\/j.nicl.2018.11.012","article-title":"Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome","volume":"21","author":"Witt","year":"2019","journal-title":"Neuroimage Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1136\/gutjnl-2016-313425","article-title":"Dietary and pharmacological treatment of abdominal pain in IBS","volume":"66","author":"Camilleri","year":"2017","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bellini, M., Tonarelli, S., Nagy, A.G., Pancetti, A., Costa, F., Ricchiuti, A., de Bortoli, N., Mosca, M., Marchi, S., and Rossi, A. (2020). Low FODMAP Diet: Evidence, doubts, and hopes. Nutrients, 12.","DOI":"10.3390\/nu12010148"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1136\/gutjnl-2017-313750","article-title":"The low FODMAP diet: Recent advances in understanding its mechanisms and efficacy in IBS","volume":"66","author":"Staudacher","year":"2017","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.cgh.2008.02.058","article-title":"Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: Randomized placebo-controlled evidence","volume":"6","author":"Shepherd","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1053\/j.gastro.2019.10.037","article-title":"Lactose and fructo-oligosaccharides increase visceral sensitivity in mice via glycation processes, increasing mast cell density in colonic mucosa","volume":"158","author":"Kamphuis","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tox.2010.09.001","article-title":"Bacterial metabolic \u2018toxins\u2019: A new mechanism for lactose and food intolerance, and irritable bowel syndrome","volume":"278","author":"Campbell","year":"2010","journal-title":"Toxicology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1172\/JCI92390","article-title":"FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e146529","DOI":"10.1172\/jci.insight.146529","article-title":"High FODMAP diet causes barrier loss via lipopolysaccharide-mediated mast cell activation","volume":"6","author":"Singh","year":"2021","journal-title":"JCI Insight"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/j.1365-2036.2010.04237.x","article-title":"Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon","volume":"31","author":"Barrett","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1136\/gutjnl-2021-325214","article-title":"Efficacy of a low FODMAP diet in irritable bowel syndrome: Systematic review and network meta-analysis","volume":"71","author":"Black","year":"2022","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13675","DOI":"10.1111\/nmo.13675","article-title":"The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome","volume":"31","author":"Tuck","year":"2019","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1001\/jama.2020.0691","article-title":"The Low-FODMAP diet helps IBS symptoms, but questions remain","volume":"323","author":"Slomski","year":"2020","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e22297","DOI":"10.1096\/fj.202100494RRR","article-title":"Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts","volume":"36","author":"Kamphuis","year":"2022","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1053\/j.gastro.2006.11.039","article-title":"Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome","volume":"132","author":"Barbara","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/apt.16812","article-title":"Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome","volume":"55","author":"Wu","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000503775","article-title":"Microcirculation: Physiology, pathophysiology, and clinical application","volume":"49","author":"Guven","year":"2020","journal-title":"Blood Purif."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"782","DOI":"10.2741\/4616","article-title":"Immune response to systemic inflammation in the intestinal microcirculation","volume":"23","author":"Thorburn","year":"2018","journal-title":"Front. Biosci. Landmark Ed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1006\/jsre.2000.5862","article-title":"Regulation of intestinal blood flow","volume":"93","author":"Matheson","year":"2000","journal-title":"J. Surg. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1572-0241.2004.04097.x","article-title":"Occurrence of colon ischemia in relation to irritable bowel syndrome","volume":"99","author":"Cole","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.3748\/wjg.v23.i47.8321","article-title":"Fructo-oligosaccharide intensifies visceral hypersensitivity and intestinal inflammation in a stress-induced irritable bowel syndrome mouse model","volume":"23","author":"Chen","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"G42","DOI":"10.1152\/ajpgi.00500.2004","article-title":"Repeated exposure to water avoidance stress in rats: A new model for sustained visceral hyperalgesia","volume":"289","author":"Bradesi","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509681","DOI":"10.3389\/fpsyt.2020.509681","article-title":"Animal models for functional gastrointestinal disorders","volume":"11","author":"Accarie","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"803957","DOI":"10.3389\/fnins.2021.803957","article-title":"Maternal separation induced visceral hypersensitivity evaluated via novel and small size distention balloon in post-weaning mice","volume":"15","author":"Tao","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41377-021-00682-8","article-title":"Transmissive-detected laser speckle contrast imaging for blood flow monitoring in thick tissue: From Monte Carlo simulation to experimental demonstration","volume":"10","author":"Li","year":"2021","journal-title":"Light Sci. Appl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ejvs.2018.08.055","article-title":"Volume based resuscitation and intestinal microcirculation after ischaemia\/reperfusion injury: Results of an exploratory aortic clamping study in pigs","volume":"57","author":"Behem","year":"2019","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"080901","DOI":"10.1117\/1.JBO.24.8.080901","article-title":"Clinical applications of laser speckle contrast imaging: A review","volume":"24","author":"Heeman","year":"2019","journal-title":"J. Biomed. Opt."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/254056a0","article-title":"In vivo evaluation of microcirculation by coherent light scattering","volume":"254","author":"Stern","year":"1975","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C350","DOI":"10.1152\/ajpcell.00191.2015","article-title":"Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A review in the Theme: Cellular responses to hypoxia","volume":"309","author":"Zheng","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1364\/BOE.10.002010","article-title":"Application of laser speckle contrast imaging in laparoscopic surgery","volume":"10","author":"Heeman","year":"2019","journal-title":"Biomed. Opt. Express"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1109\/TNSRE.2009.2012499","article-title":"Influences of Hypothermia on the cortical blood supply by laser speckle imaging","volume":"17","author":"Li","year":"2009","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1053\/j.gastro.2019.09.024","article-title":"Effects of low FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial","volume":"158","author":"Cox","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1136\/gutjnl-2014-307264","article-title":"Diets that differ in their FODMAP content alter the colonic luminal microenvironment","volume":"64","author":"Halmos","year":"2015","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1136\/gutjnl-2015-311339","article-title":"FODMAPs alter symptoms and the metabolome of patients with IBS: A randomised controlled trial","volume":"66","author":"McIntosh","year":"2017","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/j.clnu.2020.10.013","article-title":"Gut microbiota associations with diet in irritable bowel syndrome and the effect of low FODMAP diet and probiotics","volume":"40","author":"Staudacher","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1016\/j.cell.2022.09.007","article-title":"Mucus-degrading bacteroides link carbapenems to aggravated graft-versus-host disease","volume":"185","author":"Hayase","year":"2022","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrgastro.2011.83","article-title":"New insights into visceral hypersensitivity--clinical implications in IBS","volume":"8","author":"Zhou","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/0016-5085(95)90267-8","article-title":"Altered rectal perception is a biological marker of patients with irritable bowel syndrome","volume":"109","author":"Mertz","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1572-0241.2003.04012.x","article-title":"Rectal function and bowel habit in irritable bowel syndrome","volume":"99","author":"Distrutti","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1053\/gast.2002.33601","article-title":"Rectal distention testing in patients with irritable bowel syndrome: Sensitivity, specificity, and predictive values of pain sensory thresholds","volume":"122","author":"Bouin","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Vannucchi, M.G., and Evangelista, S. (2018). Experimental models of irritable bowel syndrome and the role of the enteric neurotransmission. J. Clin. Med., 7.","DOI":"10.3390\/jcm7010004"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1111\/apt.16550","article-title":"Review article: Current and future treatment approaches for pain in IBS","volume":"54","author":"Paine","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1136\/gutjnl-2020-321530","article-title":"Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS","volume":"70","author":"Perna","year":"2021","journal-title":"Gut"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in signaling and disease: Beyond discovery and development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1124\/jpet.108.145128","article-title":"Neutralizing anti-vascular endothelial growth factor (VEGF) antibody reduces severity of experimental ulcerative colitis in rats: Direct evidence for the pathogenic role of VEGF","volume":"328","author":"Tolstanova","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S2468-1253(16)30023-1","article-title":"Pathophysiology of irritable bowel syndrome","volume":"1","author":"Holtmann","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1590\/1516-3180.2018.0274161118","article-title":"Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: A cross-sectional analytical study","volume":"136","author":"Aksoy","year":"2018","journal-title":"Sao Paulo Med. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1017\/S000711451400018X","article-title":"Effect of Triticum turgidum subsp. turanicum wheat on irritable bowel syndrome: A double-blinded randomised dietary intervention trial","volume":"111","author":"Sofi","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mehy.2008.09.019","article-title":"Choir singing and fibrinogen. VEGF, cholecystokinin and motilin in IBS patients","volume":"72","author":"Theorell","year":"2009","journal-title":"Med. Hypotheses"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0002-9440(10)64869-9","article-title":"Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo","volume":"160","author":"Joussen","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/brain\/awab387","article-title":"VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer\u2019s mice","volume":"145","author":"Ali","year":"2022","journal-title":"Brain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/RHU.0000000000000089","article-title":"Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: A review of case-control studies","volume":"20","author":"Mora","year":"2014","journal-title":"J. Clin. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e14275","DOI":"10.1111\/nmo.14275","article-title":"The effects of slow deep breathing on microvascular and autonomic function and symptoms in adults with irritable bowel syndrome: A pilot study","volume":"34","author":"Seavey","year":"2022","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1365-2982.2007.01039.x","article-title":"Characterization of autonomic dysfunction in patients with irritable bowel syndrome using fingertip blood flow","volume":"20","author":"Tanaka","year":"2008","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1136\/gut.46.2.212","article-title":"Laser doppler flowmetry as a measure of extrinsic colonic innervation in functional bowel disease","volume":"46","author":"Emmanuel","year":"2000","journal-title":"Gut"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0002-9610(69)90308-0","article-title":"Pathophysiologic effects of bowel distention on intestinal blood flow","volume":"117","author":"Boley","year":"1969","journal-title":"Am. J. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109324","DOI":"10.1016\/j.mehy.2019.109324","article-title":"Hypothesis: Mechanism of irritable bowel syndrome in inflammatory bowel disease","volume":"132","author":"Uno","year":"2019","journal-title":"Med. Hypotheses"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/5\/1155\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:04Z","timestamp":1760121724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/5\/1155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":67,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["nu15051155"],"URL":"https:\/\/doi.org\/10.3390\/nu15051155","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}