{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T20:25:05Z","timestamp":1787430305888,"version":"build-2736575974"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100024662","name":"Salix Pharmaceuticals","doi-asserted-by":"publisher","award":["Technical editorial support"],"award-info":[{"award-number":["Technical editorial support"]}],"id":[{"id":"10.13039\/100024662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100024662","name":"Salix Pharmaceuticals","doi-asserted-by":"publisher","award":["Open access\/rapid fee funding"],"award-info":[{"award-number":["Open access\/rapid fee funding"]}],"id":[{"id":"10.13039\/100024662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100024662","name":"Salix Pharmaceuticals","doi-asserted-by":"publisher","award":["Employee salary"],"award-info":[{"award-number":["Employee salary"]}],"id":[{"id":"10.13039\/100024662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s12325-026-03645-w","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:15:00Z","timestamp":1781255700000},"page":"3685-3700","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irritable Bowel Syndrome with Constipation: Diagnosis and Multisymptom Management Beyond Abdominal Pain and Bowel Movement Frequency: A Review"],"prefix":"10.1007","volume":"43","author":[{"given":"Eric D.","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nijmeh","family":"Curren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Laitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Staller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"issue":"1","key":"3645_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1053\/j.gastro.2020.04.014","volume":"160","author":"AD Sperber","year":"2021","unstructured":"Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3. https:\/\/doi.org\/10.1053\/j.gastro.2020.04.014.","journal-title":"Gastroenterology"},{"issue":"1","key":"3645_CR2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.mayocp.2016.10.012","volume":"92","author":"RS Choung","year":"2017","unstructured":"Choung RS, Unalp-Arida A, Ruhl CE, Brantner TL, Everhart JE, Murray JA. Less hidden celiac disease but increased gluten avoidance without a diagnosis in the United States: findings from the National Health and Nutrition Examination Surveys from 2009 to 2014. Mayo Clin Proc. 2017;92(1):30\u20138. https:\/\/doi.org\/10.1016\/j.mayocp.2016.10.012.","journal-title":"Mayo Clin Proc"},{"issue":"4","key":"3645_CR3","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1093\/ibd\/izz182","volume":"26","author":"Y Ye","year":"2020","unstructured":"Ye Y, Manne S, Treem WR, Bennett D. Prevalence of inflammatory bowel disease in pediatric and adult populations: recent estimates from large national databases in the United States, 2007-2016. Inflamm Bowel Dis. 2020;26(4):619\u201325. https:\/\/doi.org\/10.1093\/ibd\/izz182.","journal-title":"Inflamm Bowel Dis"},{"issue":"6","key":"3645_CR4","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","volume":"150","author":"BE Lacy","year":"2016","unstructured":"Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393\u2013407. https:\/\/doi.org\/10.1053\/j.gastro.2016.02.031.","journal-title":"Gastroenterology"},{"issue":"10","key":"3645_CR5","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/s2468-1253(20)30217-x","volume":"5","author":"P Oka","year":"2020","unstructured":"Oka P, Parr H, Barberio B, Black CJ, Savarino EV, Ford AC. Global prevalence of irritable bowel syndrome according to Rome\u00a0III or IV criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(10):908\u201317. https:\/\/doi.org\/10.1016\/s2468-1253(20)30217-x.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"6","key":"3645_CR6","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1053\/j.gastro.2023.08.010","volume":"165","author":"CV Almario","year":"2023","unstructured":"Almario CV, Sharabi E, Chey WD, Lauzon M, Higgins CS, Spiegel BMR. Prevalence and burden of illness of Rome\u00a0IV irritable bowel syndrome in the United States: results from a nationwide cross-sectional study. Gastroenterology. 2023;165(6):1475\u201387. https:\/\/doi.org\/10.1053\/j.gastro.2023.08.010.","journal-title":"Gastroenterology"},{"key":"3645_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s13030-016-0070-8","volume":"10","author":"M Kanazawa","year":"2016","unstructured":"Kanazawa M, Miwa H, Nakagawa A, Kosako M, Akiho H, Fukudo S. Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based internet survey in Japan. Biopsychosoc Med. 2016;10:19. https:\/\/doi.org\/10.1186\/s13030-016-0070-8.","journal-title":"Biopsychosoc Med"},{"issue":"11","key":"3645_CR8","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14903","volume":"36","author":"BE Lacy","year":"2024","unstructured":"Lacy BE, Xu Y, Taylor DCA, et al. Burden of illness and treatment attitudes among participants meeting Rome\u00a0IV criteria for irritable bowel syndrome: a nationwide survey in the United States. Neurogastroenterol Motil. 2024;36(11):e14903. https:\/\/doi.org\/10.1111\/nmo.14903.","journal-title":"Neurogastroenterol Motil"},{"issue":"2","key":"3645_CR9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.5056\/jnm17112","volume":"24","author":"ED Shah","year":"2018","unstructured":"Shah ED, Almario CV, Spiegel BMR, Chey WD. Lower and upper gastrointestinal symptoms differ between individuals with irritable bowel syndrome with constipation or chronic idiopathic constipation. J Neurogastroenterol Motil. 2018;24(2):299\u2013306. https:\/\/doi.org\/10.5056\/jnm17112.","journal-title":"J Neurogastroenterol Motil"},{"key":"3645_CR10","unstructured":"Patients with irritable bowel syndrome with constipation from the IBS in America 2024 real-world survey experience burdensome symptoms beyond constipation. Gastroenterol Hepatol. 2024;20(12 Suppl 9):5\u20137."},{"issue":"10","key":"3645_CR11","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1080\/13696998.2020.1799816","volume":"23","author":"DCA Taylor","year":"2020","unstructured":"Taylor DCA, Abel JL, Martin C, et al. Comprehensive assessment of patients with irritable bowel syndrome with constipation and chronic idiopathic constipation using deterministically linked administrative claims and patient-reported data: the Chronic Constipation and IBS-C Treatment and Outcomes Real-World Research Platform (CONTOR). J Med Econ. 2020;23(10):1072\u201383. https:\/\/doi.org\/10.1080\/13696998.2020.1799816.","journal-title":"J Med Econ"},{"issue":"11","key":"3645_CR12","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1185\/03007995.2011.623157","volume":"27","author":"M DiBonaventura","year":"2011","unstructured":"DiBonaventura M, Sun SX, Bolge SC, Wagner JS, Mody R. Health-related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome. Curr Med Res Opin. 2011;27(11):2213\u201322. https:\/\/doi.org\/10.1185\/03007995.2011.623157.","journal-title":"Curr Med Res Opin"},{"issue":"12","key":"3645_CR13","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1016\/j.cgh.2019.08.016","volume":"17","author":"S Ballou","year":"2019","unstructured":"Ballou S, McMahon C, Lee HN, et al. Effects of irritable bowel syndrome on daily activities vary among subtypes based on results from the IBS in America survey. Clin Gastroenterol Hepatol. 2019;17(12):2471-78.e3. https:\/\/doi.org\/10.1016\/j.cgh.2019.08.016.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"12","key":"3645_CR14","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1111\/apt.16369","volume":"53","author":"A Sharma","year":"2021","unstructured":"Sharma A, Rao SSC, Kearns K, Orleck KD, Waldman SA. Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders. Aliment Pharmacol Ther. 2021;53(12):1250\u201367. https:\/\/doi.org\/10.1111\/apt.16369.","journal-title":"Aliment Pharmacol Ther"},{"issue":"6","key":"3645_CR15","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1093\/jcag\/gwad028","volume":"6","author":"G Bhinder","year":"2023","unstructured":"Bhinder G, Meza-Cardona JM, Low A, Aumais G, Attara GP, Gray JR. Irritable bowel syndrome patient experience: a survey of patient-reported symptoms by irritable bowel syndrome subtype and impact on quality of life. J Can Assoc Gastroenterol. 2023;6(6):219\u201328. https:\/\/doi.org\/10.1093\/jcag\/gwad028.","journal-title":"J Can Assoc Gastroenterol"},{"issue":"4","key":"3645_CR16","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ajg.2015.67","volume":"110","author":"JJ Heidelbaugh","year":"2015","unstructured":"Heidelbaugh JJ, Stelwagon M, Miller SA, Shea EP, Chey WD. The spectrum of constipation-predominant irritable bowel syndrome and chronic idiopathic constipation: US survey assessing symptoms, care seeking, and disease burden. Am J Gastroenterol. 2015;110(4):580\u20137. https:\/\/doi.org\/10.1038\/ajg.2015.67.","journal-title":"Am J Gastroenterol"},{"issue":"5 suppl 3","key":"3645_CR17","first-page":"3","volume":"14","author":"BD Cash","year":"2018","unstructured":"Cash BD. Understanding and managing IBS and CIC in the primary care setting. Gastroenterol Hepatol (NY). 2018;14(5 suppl 3):3\u201315.","journal-title":"Gastroenterol Hepatol (NY)"},{"key":"3645_CR18","doi-asserted-by":"publisher","unstructured":"Lacy BE, Pimentel M, Brenner DM, et al. ACG Clinical Guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021; 116(1):17\u201344. https:\/\/doi.org\/10.14309\/ajg.0000000000001036.","DOI":"10.14309\/ajg.0000000000001036"},{"issue":"3","key":"3645_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14004","volume":"33","author":"AL Engsbro","year":"2021","unstructured":"Engsbro AL, Begtrup LM, Haastrup P, et al. A positive diagnostic strategy is safe and saves endoscopies in patients with irritable bowel syndrome: a five-year follow-up of a randomized controlled trial. Neurogastroenterol Motil. 2021;33(3):e14004. https:\/\/doi.org\/10.1111\/nmo.14004.","journal-title":"Neurogastroenterol Motil"},{"issue":"3","key":"3645_CR20","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1053\/j.gastro.2021.11.019","volume":"162","author":"DA Drossman","year":"2022","unstructured":"Drossman DA, Tack J. Rome Foundation clinical diagnostic criteria for disorders of gut-brain interaction. Gastroenterology. 2022;162(3):675\u20139. https:\/\/doi.org\/10.1053\/j.gastro.2021.11.019.","journal-title":"Gastroenterology"},{"issue":"1","key":"3645_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66369-z","volume":"10","author":"YR Chen","year":"2020","unstructured":"Chen YR, Zheng HM, Zhang GX, Chen FL, Chen LD, Yang ZC. High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project. Sci Rep. 2020;10(1):9364. https:\/\/doi.org\/10.1038\/s41598-020-66369-z.","journal-title":"Sci Rep"},{"key":"3645_CR22","doi-asserted-by":"publisher","unstructured":"Villanueva-Millan MJ, Leite G, Wang J, et al. Methanogens and hydrogen sulfide producing bacteria guide distinct gut microbe profiles and irritable bowel syndrome subtypes. Am J Gastroenterol. 2022;117(12):2055\u201366. https:\/\/doi.org\/10.14309\/ajg.0000000000001997.","DOI":"10.14309\/ajg.0000000000001997"},{"issue":"6","key":"3645_CR23","doi-asserted-by":"publisher","first-page":"932","DOI":"10.5009\/gnl15588","volume":"10","author":"U Ghoshal","year":"2016","unstructured":"Ghoshal U, Shukla R, Srivastava D, Ghoshal UC. Irritable bowel syndrome, particularly the constipation-predominant form, involves an increase in Methanobrevibacter smithii, which is associated with higher methane production. Gut Liver. 2016;10(6):932\u20138. https:\/\/doi.org\/10.5009\/gnl15588.","journal-title":"Gut Liver"},{"issue":"12","key":"3645_CR24","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1007\/s10620-012-2197-1","volume":"57","author":"G Kim","year":"2012","unstructured":"Kim G, Deepinder F, Morales W, et al. Methanobrevibacter smithii is the predominant methanogen in patients with constipation-predominant IBS and methane on breath. Dig Dis Sci. 2012;57(12):3213\u20138. https:\/\/doi.org\/10.1007\/s10620-012-2197-1.","journal-title":"Dig Dis Sci"},{"issue":"3","key":"3645_CR25","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1053\/j.gastro.2023.04.039","volume":"165","author":"B Moshiree","year":"2023","unstructured":"Moshiree B, Drossman D, Shaukat A. AGA Clinical Practice Update on evaluation and management of belching, abdominal bloating, and distention: expert review. Gastroenterology. 2023;165(3):791\u2013800. https:\/\/doi.org\/10.1053\/j.gastro.2023.04.039.","journal-title":"Gastroenterology"},{"issue":"4","key":"3645_CR26","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1053\/j.gastro.2020.06.090","volume":"159","author":"EMM Quigley","year":"2020","unstructured":"Quigley EMM, Murray JA, Pimentel M. AGA Clinical Practice Update on small intestinal bacterial overgrowth: expert review. Gastroenterology. 2020;159(4):1526\u201332. https:\/\/doi.org\/10.1053\/j.gastro.2020.06.090.","journal-title":"Gastroenterology"},{"issue":"3","key":"3645_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11030573","volume":"11","author":"M Banaszak","year":"2023","unstructured":"Banaszak M, G\u00f3rna I, Wo\u017aniak D, Przys\u0142awski J, Drzyma\u0142a-Czy\u017c S. Association between gut dysbiosis and the occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms. 2023;11(3):573. https:\/\/doi.org\/10.3390\/microorganisms11030573.","journal-title":"Microorganisms"},{"issue":"5","key":"3645_CR28","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/ajg.2017.46","volume":"112","author":"A Rezaie","year":"2017","unstructured":"Rezaie A, Buresi M, Lembo A, et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American Consensus. Am J Gastroenterol. 2017;112(5):775\u201384. https:\/\/doi.org\/10.1038\/ajg.2017.46.","journal-title":"Am J Gastroenterol"},{"issue":"7","key":"3645_CR29","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.cgh.2024.07.020","volume":"23","author":"S Mehravar","year":"2025","unstructured":"Mehravar S, Takakura W, Wang J, Pimentel M, Nasser J, Rezaie A. Symptom profile of patients with intestinal methanogen overgrowth: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2025;23(7):1111\u201322. https:\/\/doi.org\/10.1016\/j.cgh.2024.07.020.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"20","key":"3645_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11206017","volume":"11","author":"B Skrzyd\u0142o-Radoma\u0144ska","year":"2022","unstructured":"Skrzyd\u0142o-Radoma\u0144ska B, Cukrowska B. How to recognize and treat small intestinal bacterial overgrowth? J Clin Med. 2022;11(20):6017. https:\/\/doi.org\/10.3390\/jcm11206017.","journal-title":"J Clin Med"},{"issue":"6","key":"3645_CR31","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1007\/s10620-014-3157-8","volume":"59","author":"M Pimentel","year":"2014","unstructured":"Pimentel M, Chang C, Chua KS, et al. Antibiotic treatment of constipation-predominant irritable bowel syndrome. Dig Dis Sci. 2014;59(6):1278\u201385. https:\/\/doi.org\/10.1007\/s10620-014-3157-8.","journal-title":"Dig Dis Sci"},{"issue":"4","key":"3645_CR32","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/j.1572-0241.2007.01072.x","volume":"102","author":"S Chatterjee","year":"2007","unstructured":"Chatterjee S, Park S, Low K, Kong Y, Pimentel M. The degree of breath methane production in IBS correlates with the severity of constipation. Am J Gastroenterol. 2007;102(4):837\u201341. https:\/\/doi.org\/10.1111\/j.1572-0241.2007.01072.x.","journal-title":"Am J Gastroenterol"},{"key":"3645_CR33","doi-asserted-by":"publisher","unstructured":"Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010;44(8):547\u201350. https:\/\/doi.org\/10.1097\/MCG.0b013e3181c64c90.","DOI":"10.1097\/MCG.0b013e3181c64c90"},{"key":"3645_CR34","doi-asserted-by":"publisher","unstructured":"Major G, Pritchard S, Murray K, et al. Colon hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in individuals with irritable bowel syndrome. Gastroenterology. 2017;152(1):124\u201333 e2. https:\/\/doi.org\/10.1053\/j.gastro.2016.09.062.","DOI":"10.1053\/j.gastro.2016.09.062"},{"issue":"2","key":"3645_CR35","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1097\/MOG.0000000000000608","volume":"36","author":"BP Chumpitazi","year":"2020","unstructured":"Chumpitazi BP. The gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disorders. Curr Opin Gastroenterol. 2020;36(2):147\u201354. https:\/\/doi.org\/10.1097\/MOG.0000000000000608.","journal-title":"Curr Opin Gastroenterol"},{"key":"3645_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.630249","volume":"12","author":"Q Zhao","year":"2021","unstructured":"Zhao Q, Chen YY, Xu DQ, et al. Action mode of gut motility, fluid and electrolyte transport in chronic constipation. Front Pharmacol. 2021;12:630249. https:\/\/doi.org\/10.3389\/fphar.2021.630249.","journal-title":"Front Pharmacol"},{"key":"3645_CR37","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2147\/CEG.S454526","volume":"17","author":"P Singh","year":"2024","unstructured":"Singh P, Sayuk GS, Rosenbaum DP, Edelstein S, Kozuka K, Chang L. An overview of the effects of tenapanor on visceral hypersensitivity in the treatment of irritable bowel syndrome with constipation. Clin Exp Gastroenterol. 2024;17:87\u201396. https:\/\/doi.org\/10.2147\/CEG.S454526.","journal-title":"Clin Exp Gastroenterol"},{"issue":"2","key":"3645_CR38","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.tips.2021.11.002","volume":"43","author":"SM Brierley","year":"2022","unstructured":"Brierley SM, Grundy L, Castro J, Harrington AM, Hannig G, Camilleri M. Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. Trends Pharmacol Sci. 2022;43(2):110\u201322. https:\/\/doi.org\/10.1016\/j.tips.2021.11.002.","journal-title":"Trends Pharmacol Sci"},{"issue":"2","key":"3645_CR39","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1159\/000543166","volume":"43","author":"DM Brenner","year":"2025","unstructured":"Brenner DM, Sayuk GS, Cash BD, et al. Tenapanor improves abdominal symptoms irrespective of changes in complete spontaneous bowel movement frequency in adults with irritable bowel syndrome with constipation. Dig Dis. 2025;43(2):146\u201357. https:\/\/doi.org\/10.1159\/000543166.","journal-title":"Dig Dis"},{"issue":"12","key":"3645_CR40","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1111\/apt.15772","volume":"51","author":"SSC Rao","year":"2020","unstructured":"Rao SSC, Xiang X, Yan Y, et al. Randomised clinical trial: linaclotide vs placebo\u2014a study of bi-directional gut and brain axis. Aliment Pharmacol Ther. 2020;51(12):1332\u201341. https:\/\/doi.org\/10.1111\/apt.15772.","journal-title":"Aliment Pharmacol Ther"},{"issue":"1","key":"3645_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-04898-1","volume":"22","author":"J Zhou","year":"2024","unstructured":"Zhou J, Wei H, Zhou A, et al. The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study. J Transl Med. 2024;22(1):98. https:\/\/doi.org\/10.1186\/s12967-024-04898-1.","journal-title":"J Transl Med"},{"issue":"5","key":"3645_CR42","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/s41395-018-0026-7","volume":"113","author":"DM Brenner","year":"2018","unstructured":"Brenner DM, Fogel R, Dorn SD, et al. Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase\u00a03 randomized clinical trials. Am J Gastroenterol. 2018;113(5):735\u201345. https:\/\/doi.org\/10.1038\/s41395-018-0026-7.","journal-title":"Am J Gastroenterol"},{"key":"3645_CR43","doi-asserted-by":"publisher","unstructured":"Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714\u201324; quiz p25. https:\/\/doi.org\/10.1038\/ajg.2012.255.","DOI":"10.1038\/ajg.2012.255"},{"issue":"11","key":"3645_CR44","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1038\/ajg.2012.254","volume":"107","author":"WD Chey","year":"2012","unstructured":"Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107(11):1702\u201312. https:\/\/doi.org\/10.1038\/ajg.2012.254.","journal-title":"Am J Gastroenterol"},{"issue":"3","key":"3645_CR45","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/j.1365-2036.2008.03881.x","volume":"29","author":"DA Drossman","year":"2009","unstructured":"Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome\u2014results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29(3):329\u201341. https:\/\/doi.org\/10.1111\/j.1365-2036.2008.03881.x.","journal-title":"Aliment Pharmacol Ther"},{"key":"3645_CR46","doi-asserted-by":"publisher","unstructured":"Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 12-week, placebo-controlled phase\u00a03 trial (T3MPO-1). Am J Gastroenterol. 2020;115(2):281\u201393. https:\/\/doi.org\/10.14309\/ajg.0000000000000516.","DOI":"10.14309\/ajg.0000000000000516"},{"key":"3645_CR47","doi-asserted-by":"publisher","unstructured":"Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 26-week, placebo-controlled phase\u00a03 trial (T3MPO-2). Am J Gastroenterol. 2021;116(6):1294\u2013303. https:\/\/doi.org\/10.14309\/ajg.0000000000001056.","DOI":"10.14309\/ajg.0000000000001056"},{"issue":"2","key":"3645_CR48","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.cgh.2020.03.056","volume":"19","author":"BE Lacy","year":"2021","unstructured":"Lacy BE, Cangemi D, Vazquez-Roque M. Management of chronic abdominal distension and bloating. Clin Gastroenterol Hepatol. 2021;19(2):219\u201331. https:\/\/doi.org\/10.1016\/j.cgh.2020.03.056.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"3645_CR49","doi-asserted-by":"publisher","unstructured":"Neri L, Iovino P, Laxative Inadequate Relief Survey (LIRS) Group. Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation. Neurogastroenterol Motil. 2016;28(4):581\u201391. https:\/\/doi.org\/10.1111\/nmo.12758.","DOI":"10.1111\/nmo.12758"},{"issue":"5","key":"3645_CR50","first-page":"301","volume":"99","author":"JM Wilkinson","year":"2019","unstructured":"Wilkinson JM, Cozine EW, Loftus CG. Gas, bloating, and belching: approach to evaluation and management. Am Fam Physician. 2019;99(5):301\u20139.","journal-title":"Am Fam Physician"},{"issue":"2","key":"3645_CR51","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/apt.16437","volume":"54","author":"AD Nelson","year":"2021","unstructured":"Nelson AD, Black CJ, Houghton LA, Lugo-Fagundo NS, Lacy BE, Ford AC. Systematic review and network meta-analysis: efficacy of licensed drugs for abdominal bloating in irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2021;54(2):98\u2013108. https:\/\/doi.org\/10.1111\/apt.16437.","journal-title":"Aliment Pharmacol Ther"},{"key":"3645_CR52","doi-asserted-by":"publisher","unstructured":"Chang L, Lacy BE, Moshiree B, et al. Efficacy of linaclotide in reducing abdominal symptoms of bloating, discomfort, and pain: a phase\u00a03b trial using a novel abdominal scoring system. Am J Gastroenterol. 2021;116(9):1929\u201337. https:\/\/doi.org\/10.14309\/ajg.0000000000001334.","DOI":"10.14309\/ajg.0000000000001334"},{"issue":"12","key":"3645_CR53","doi-asserted-by":"publisher","first-page":"2890","DOI":"10.1111\/jgh.70119","volume":"40","author":"DM Brenner","year":"2025","unstructured":"Brenner DM, Shin AS, Laitman AP, Deutsch JK, Kunkel DC. The effectiveness of plecanatide for treating constipation and bloating in patients aged 18 to 40\u00a0years with irritable bowel syndrome: utilization of a new composite trisymptom endpoint. J Gastroenterol Hepatol. 2025;40(12):2890\u20137. https:\/\/doi.org\/10.1111\/jgh.70119.","journal-title":"J Gastroenterol Hepatol"},{"issue":"5","key":"3645_CR54","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1007\/s10620-024-08330-y","volume":"69","author":"DM Brenner","year":"2024","unstructured":"Brenner DM, Sharma A, Rao SSC, et al. Plecanatide improves abdominal bloating and bowel symptoms of irritable bowel syndrome with constipation. Dig Dis Sci. 2024;69(5):1731\u20138. https:\/\/doi.org\/10.1007\/s10620-024-08330-y.","journal-title":"Dig Dis Sci"},{"issue":"5","key":"3645_CR55","doi-asserted-by":"publisher","first-page":"937","DOI":"10.14309\/ajg.0000000000002685","volume":"119","author":"AJ Lembo","year":"2024","unstructured":"Lembo AJ, Chey WD, Harris LA, et al. Abdominal symptom improvement during clinical trials of tenapanor in patients with irritable bowel syndrome with constipation: a post hoc analysis. Am J Gastroenterol. 2024;119(5):937\u201345. https:\/\/doi.org\/10.14309\/ajg.0000000000002685.","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"3645_CR56","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/S2468-1253(25)00051-2","volume":"10","author":"M Khasawneh","year":"2025","unstructured":"Khasawneh M, Mokhtare M, Moayyedi P, Black CJ, Ford AC. Efficacy of gut-brain neuromodulators in irritable bowel syndrome: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2025;10(6):537\u201349. https:\/\/doi.org\/10.1016\/S2468-1253(25)00051-2.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"3","key":"3645_CR57","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/apt.16467","volume":"54","author":"B Nulsen","year":"2021","unstructured":"Nulsen B, LeBrett W, Drossman DA, Chang L. A survey of gastroenterologists in the United States on the use of central neuromodulators for treating irritable bowel syndrome. Aliment Pharmacol Ther. 2021;54(3):281\u201391. https:\/\/doi.org\/10.1111\/apt.16467.","journal-title":"Aliment Pharmacol Ther"},{"issue":"7","key":"3645_CR58","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.14309\/ajg.0000000000002800","volume":"119","author":"I Hanna-Jairala","year":"2024","unstructured":"Hanna-Jairala I, Drossman DA. Central neuromodulators in irritable bowel syndrome: why, how, and when. Am J Gastroenterol. 2024;119(7):1272\u201384. https:\/\/doi.org\/10.14309\/ajg.0000000000002800.","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"3645_CR59","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1053\/j.gastro.2017.11.279","volume":"154","author":"DA Drossman","year":"2018","unstructured":"Drossman DA, Tack J, Ford AC, Szigethy E, T\u00f6rnblom H, Van Oudenhove L. Neuromodulators for functional gastrointestinal disorders (disorders of gut-brain interaction): a Rome Foundation Working Team report. Gastroenterology. 2018;154(4):1140\u201371. https:\/\/doi.org\/10.1053\/j.gastro.2017.11.279.","journal-title":"Gastroenterology"},{"issue":"8","key":"3645_CR60","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1136\/gut.2005.077503","volume":"55","author":"J Tack","year":"2006","unstructured":"Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55(8):1095\u2013103. https:\/\/doi.org\/10.1136\/gut.2005.077503.","journal-title":"Gut"},{"issue":"3","key":"3645_CR61","doi-asserted-by":"publisher","first-page":"284","DOI":"10.20524\/aog.2025.0962","volume":"38","author":"MJ Temido","year":"2025","unstructured":"Temido MJ, Cristiano M, Gouveia C, Mesquita B, Figueiredo P, Portela F. Antidepressants in irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Ann Gastroenterol. 2025;38(3):284\u201393. https:\/\/doi.org\/10.20524\/aog.2025.0962.","journal-title":"Ann Gastroenterol"},{"issue":"10414","key":"3645_CR62","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1016\/S0140-6736(23)01523-4","volume":"402","author":"AC Ford","year":"2023","unstructured":"Ford AC, Wright-Hughes A, Alderson SL, et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase\u00a03 trial. Lancet. 2023;402(10414):1773\u201385. https:\/\/doi.org\/10.1016\/S0140-6736(23)01523-4.","journal-title":"Lancet"},{"issue":"5","key":"3645_CR63","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1365-2036.2005.02566.x","volume":"22","author":"H Vahedi","year":"2005","unstructured":"Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther. 2005;22(5):381\u20135. https:\/\/doi.org\/10.1111\/j.1365-2036.2005.02566.x.","journal-title":"Aliment Pharmacol Ther"},{"issue":"1","key":"3645_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/s13030-021-00205-2","volume":"15","author":"A Khalilian","year":"2021","unstructured":"Khalilian A, Ahmadimoghaddam D, Saki S, Mohammadi Y, Mehrpooya M. A randomized, double-blind, placebo-controlled study to assess efficacy of mirtazapine for the treatment of diarrhea predominant irritable bowel syndrome. Biopsychosoc Med. 2021;15(1):3. https:\/\/doi.org\/10.1186\/s13030-021-00205-2.","journal-title":"Biopsychosoc Med"},{"issue":"1","key":"3645_CR65","first-page":"17","volume":"3","author":"S Sanagapalli","year":"2018","unstructured":"Sanagapalli S, Kim E, Zarate-Lopez N, Emmanuel A. Mirtazapine in diarrhea-predominant irritable bowel syndrome: an open label study. J Gastroenterol Dig Dis. 2018;3(1):17\u201321.","journal-title":"J Gastroenterol Dig Dis"},{"key":"3645_CR66","doi-asserted-by":"publisher","DOI":"10.1177\/17562848241278125","volume":"18","author":"A Khan","year":"2024","unstructured":"Khan A, Menon R, Corning B, Cohn S, Kumfa C, Raji M. Mirtazapine for gastrointestinal and neuropsychological symptoms in older adults with irritable bowel syndrome. Therap Adv Gastroenterol. 2024;18:17562848241278125. https:\/\/doi.org\/10.1177\/17562848241278125.","journal-title":"Therap Adv Gastroenterol"},{"issue":"1","key":"3645_CR67","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/WNF.0b013e318209cef2","volume":"34","author":"DR Spiegel","year":"2011","unstructured":"Spiegel DR, Kolb R. Treatment of irritable bowel syndrome with comorbid anxiety symptoms with mirtazapine. Clin Neuropharmacol. 2011;34(1):36\u20138. https:\/\/doi.org\/10.1097\/WNF.0b013e318209cef2.","journal-title":"Clin Neuropharmacol"},{"issue":"2","key":"3645_CR68","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1136\/flgastro-2019-101211","volume":"11","author":"CJ Black","year":"2020","unstructured":"Black CJ, Ford AC. Rational investigations in irritable bowel syndrome. Frontline Gastroenterol. 2020;11(2):140\u20137. https:\/\/doi.org\/10.1136\/flgastro-2019-101211.","journal-title":"Frontline Gastroenterol"},{"issue":"4","key":"3645_CR69","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1053\/j.gastro.2021.07.034","volume":"161","author":"L Chang","year":"2021","unstructured":"Chang L. How to approach a patient with difficult-to-treat IBS. Gastroenterology. 2021;161(4):1092\u201398.e3. https:\/\/doi.org\/10.1053\/j.gastro.2021.07.034.","journal-title":"Gastroenterology"},{"key":"3645_CR70","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.2147\/IJGM.S274568","volume":"14","author":"S Patel","year":"2021","unstructured":"Patel S, Doerfler B, Boutros K, Ng S, Manuel M, DeSimone E. Review of treatment options for irritable bowel syndrome with constipation and chronic idiopathic constipation. Int J Gen Med. 2021;14:1457\u201368. https:\/\/doi.org\/10.2147\/IJGM.S274568.","journal-title":"Int J Gen Med"},{"issue":"9","key":"3645_CR71","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41575-023-00794-z","volume":"20","author":"HM Staudacher","year":"2023","unstructured":"Staudacher HM, Black CJ, Teasdale SB, Mikocka-Walus A, Keefer L. Irritable bowel syndrome and mental health comorbidity\u2014approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023;20(9):582\u201396. https:\/\/doi.org\/10.1038\/s41575-023-00794-z.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"3645_CR72","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41395-018-0222-5","volume":"114","author":"AC Ford","year":"2019","unstructured":"Ford AC, Lacy BE, Harris LA, Quigley EMM, Moayyedi P. Effect of antidepressants and psychological therapies in irritable bowel syndrome: an updated systematic review and meta-analysis. Am J Gastroenterol. 2019;114(1):21\u201339. https:\/\/doi.org\/10.1038\/s41395-018-0222-5.","journal-title":"Am J Gastroenterol"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03645-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-026-03645-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03645-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T20:01:42Z","timestamp":1787428902000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-026-03645-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":72,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["3645"],"URL":"https:\/\/doi.org\/10.1007\/s12325-026-03645-w","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"21 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original article was revised due to update in Table 1.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Eric D. Shah reports being a consultant for AbbVie, Ardelyx, Cook Group, Laborie Medical Technologies, Mahana Therapeutics, Mylan (Viatris), NeurAxis, Salix Pharmaceuticals, Sanofi, and Takeda Pharmaceutical; holding stock in NeurAxis; and having a patent with the Regent of the University of Michigan. Amol Sharma is a consultant for Atmo Biosciences and has received research support from Vibrant Gastro. Nijmeh Curren and Adam P. Laitman are employees of Salix Pharmaceuticals. Kyle Staller has served as a consultant to Anji Pharmaceuticals, Ardelyx, Gemelli Biotech, Laborie Medical Technologies, Mahana Therapeutics, ReStalsis Health, Salix Pharmaceuticals, and Takeda Pharmaceutical, and has received research support from Ardelyx and ReStalsis Health.","order":1,"name":"Ethics","label":"Conflicts of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}