Across multiple ACG 2025 reports, tenapanor (50 mg BID) showed consistent benefit for IBS-C—especially bloating. In a pooled post hoc analysis of 3 trials (n=1253 with moderate to severe baseline bloating), tenapanor delivered a greater 12-week reduction vs placebo (LS mean change −2.66 vs −2.10; difference −0.57; P=.0003) with faster onset (median time to ≥30% bloating improvement 5 vs 8 weeks; P<.0001). Safety signals were largely GI, with diarrhea the most common drug-related AE (~13% vs ~2% placebo) and serious TEAEs uncommon. A meta-analysis similarly showed improvements across abdominal symptoms and CSBMs, with higher treatment-related AEs/discontinuations (again mainly diarrhea) but no clear increase in serious AEs. Real-world data echoed these findings: high satisfaction (~88%), broad symptom/quality of life (QOL) gains, and EHR signals of fewer GI visits and portal messages, especially among high utilizers.

For plecanatide (GC-C agonist), pooled phase 3 analyses showed concurrent improvements in pain, bloating, and CSBMs, including in women 18–40 with bloating; diarrhea remained the most common AE (low single-digit rates). Another post hoc analysis found plecanatide can improve HRQOL even without meeting the FDA stool-frequency responder definition (clinically meaningful IBS-QOL improvement at Week 12: 36.9% vs 28.8% placebo). A FAERS-based safety review across linaclotide, lubiprostone, plecanatide, and tenapanor found most reports were nonserious and GI, while noting FAERS can’t establish incidence/causality. In pediatrics, a meta-analysis suggested linaclotide may improve stool consistency and straining but has limited effects on CSBMs, abdominal pain, or bloating, with AE rates not clearly different from placebo.

Reference: Gastroenterology & Hepatology. Highlights in IBS-C From the American College of Gastroenterology 2025 Annual Scientific Meeting: A review of selected presentations from the ACG 2025 Annual Scientific Meeting (October 24-29, 2025; Phoenix, AZ). Gastroenterol Hepatol (N Y). 2025 Nov;21(11 Suppl 8) (Special Meeting Review Edition).

Irritable bowel syndrome (IBS) is a chronic disorder of the microbiota–gut–brain axis involving abdominal pain, altered bowel habits, visceral hypersensitivity, low-grade inflammation, impaired intestinal barrier function, and altered gut microbiota. Many studies show microbiota differences between IBS and healthy controls, but no single “IBS signature” or clear “healthy microbiota” definition has emerged due to high variability and inconsistent methods. Microbiota-targeted strategies such as the low FODMAP diet and fecal microbiota transplantation (FMT) can relieve symptoms in some patients, but results are mixed, long-term safety is uncertain, and both may affect microbial diversity and gut integrity.

To better understand IBS, researchers are combining molecular biology, advanced neuroimaging, microbiome analysis, and data science. MRI studies show reproducible changes in brain regions tied to pain and emotion, and emerging “radiomicrobiomics” links brain imaging with microbiota and metabolite data. Microbiome work is moving toward more standardized methods, metagenomics for species- and function-level detail, and richer metadata (diet, BMI, age, sex, medications) to reduce confounding. The authors conclude that multimodal, longitudinal, interdisciplinary studies integrating gut microbiota, barrier function, immune markers, neuroimaging, and clinical outcomes are essential to clarify causality in the microbiota–gut–brain axis and to guide more personalized IBS treatments.

Reference: Hillestad EMR, van der Meeren A, Nagaraja BH, et al. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J Gastroenterol. 2022 Jan 28;28(4):412-431. doi: 10.3748/wjg.v28.i4.412. PMID: 35125827; PMCID: PMC8790555.

Authors of this systematic review (2000–2024) evaluated clinical evidence for invasive and noninvasive electrical neuromodulation in irritable bowel syndrome (IBS), assessed study quality, and summarized mechanisms, side effects, and cost considerations. Invasive options—sacral nerve stimulation (SNS) and spinal cord stimulation—showed benefits for pain and quality of life (QoL) in highly selected patients, mainly IBS with diarrhea/IBS with a mixed bowel pattern. Crossover randomized controlled trials (RCTs) and follow-ups reported reduced symptom scores, fewer bowel movements, and durable QoL gains, alongside device-related adverse events (implant-site pain, lead revisions) but no life-threatening harms. Modeling suggests SNS can be cost-effective long-term.

Noninvasive approaches target the vagal/brain–gut axis with favorable safety and self-use potential. Transcutaneous auricular VNS (taVNS) improved abdominal pain, constipation, rectal sensitivity, and mood in IBS with contsipation RCTs; percutaneous auricular nerve field stimulation (PENFS) reduced pain and disability in adolescents, with exploratory microbiome shifts; and transcutaneous electrical acustimulation (TEA) improved pain, constipation, transit, and QoL in small RCTs. PENFS requires clinician placement, while taVNS/TEA are home-friendly. Overall, neuromodulation—especially taVNS, PENFS, and TEA—appears promising for IBS pain and, in IBS-C, for constipation, warranting multicenter trials to refine candidates, dosing, durability, and cost-effectiveness.

Reference: Wang K, Alam MJ, Lan X, Li F, Chen JDZ. Efficacy and mechanisms of neuromodulation in the treatment of irritable bowel syndrome. Bioelectron Med. 2025;11(1):23. doi: 10.1186/s42234-025-00186-5.

This systematic review aimed to evaluate the effectiveness of kiwifruit or kiwifruit extracts in treating constipation by analyzing randomized controlled trials (RCTs). A total of seven RCTs involving 399 participants (82% female, average age 42 years) were included. The review assessed outcomes such as the frequency of spontaneous bowel movements (SBM), abdominal pain, straining, and stool type. Compared to placebo, kiwifruit extracts may slightly increase SBM frequency with low certainty, and it had an uncertain effect on stool type with very low certainty. Kiwifruit also showed moderate evidence for reducing abdominal pain but had a negligible impact on straining.

The review found that kiwifruit might increase SBM compared to psyllium, with moderate certainty, and may also improve stool softness, though the evidence remains inconclusive. Kiwifruit extracts also potentially led to more minor adverse events than placebo. Overall, the evidence supporting kiwifruit as an effective treatment for constipation is of low certainty. While promising, researchers stress that larger and more methodologically robust studies are needed to confirm its role in constipation management.

Reference: Eltorki M, Leong R, Ratcliffe EM. Kiwifruit and Kiwifruit Extracts for Treatment of Constipation: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol. 2022 Oct 6;2022:7596920. doi: 10.1155/2022/7596920. PMID: 36247043; PMCID: PMC9560827.

Over the past decade, new therapies for irritable bowel syndrome with constipation (IBS-C) have emerged, but treatment options remain limited for patients unresponsive to secretagogues. Tenapanor, a sodium/hydrogen exchanger 3 inhibitor, offers a novel mechanism of action by reducing sodium absorption in the intestines, leading to increased intestinal fluid and softer stools. Initially developed for hyperphosphatemia, tenapanor demonstrated GI benefits and minimal systemic availability. Preclinical studies showed tenapanor reduced intestinal permeability and visceral hypersensitivity. Early-phase clinical trials confirmed its safety, tolerability, and favorable pharmacodynamics, with mild GI-related adverse events.

Tenapanor’s efficacy was further validated in Phase II and III trials, where it significantly improved both bowel function and abdominal symptoms in patients with IBS-C. The drug met FDA responder endpoints, improved quality of life scores, and was well tolerated aside from diarrhea being the most frequent side effect. Approved by the FDA in 2019, tenapanor is now a recommended option for patients with IBS-C who are unresponsive to first-line treatments like fiber or polyethylene glycol. Unlike serotonin agonists, tenapanor has no cardiovascular restrictions and presents a distinct, safe alternative. However, treatment decisions will likely continue to be shaped by cost and comparative safety data across available pharmacologic agents.

Reference: Herekar A, Shimoga D, Jehangir A, et al. Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management. Clin Exp Gastroenterol. 2023 Jun 7;16:79-85. doi: 10.2147/CEG.S384251. PMID: 37309470; PMCID: PMC10257918.

A 23-year-old biology PhD candidate has experienced gastrointestinal symptoms for the past three years, including recurrent abdominal pain, bloating, and constipation. Despite trying dietary changes (gluten-free, lactose-free, and low-FODMAP), polyethylene glycol 3350, and cognitive behavioral therapy, her symptoms persist, severely affecting her quality of life. She spends hours in the restroom, leading to missed deadlines and concerns about funding. After a thorough evaluation, she was diagnosed with irritable bowel syndrome with constipation (IBS-C) and referred to gastroenterology for further management.

IBS-C, characterized by abdominal pain and constipation, is common in women and younger individuals. It has a multifactorial pathophysiology, including gut motility changes, microbiome-immune interactions, and gut permeability. Treatments for IBS-C have evolved, with FDA-approved agents like lubiprostone, linaclotide, plecanatide, and tenapanor targeting different mechanisms to offer symptom relief. However, current therapies are not universally effective, so treatment must be individualized based on factors such as symptoms, safety, and patient preferences.

Reference: Brenner DM. Mechanism of Action Considerations in the Management of IBS-C. Gastroenterol Hepatol (N Y). 2023 Dec;19(12):749-756. PMID: 38404415; PMCID: PMC10885421.

FODMAPs are a group of short-chain carbohydrates (sugars) that are not fully digested or absorbed in the intestines. When they reach the large intestine, they attract water and are fermented by gut bacteria, producing gas. This process causes the intestinal wall to stretch, leading to pain and discomfort, especially for people with irritable bowel syndrome (IBS) who have a sensitive gut. FODMAPs are found naturally in many foods, including fruits, vegetables, dairy, grains, and certain sweeteners. Common types of FODMAPs include oligosaccharides (like fructans in wheat and garlic), disaccharides (like lactose in dairy), monosaccharides (like fructose in fruits), and polyols (like sorbitol in some fruits and artificial sweeteners).

The low FODMAP diet, developed by Monash University, helps manage IBS symptoms by eliminating high FODMAP foods and gradually reintroducing them. It has been shown to improve symptoms like pain, bloating, and altered bowel habits in many patients with IBS, with benefits usually seen within two to six weeks. The diet is recommended for people diagnosed with IBS and should be followed under the guidance of a healthcare professional. For those who do not benefit from the Low FODMAP Diet, other therapies such as stress reduction, hypnotherapy, or medications may be needed.

Reference: FODMAPs and Irritable Bowel Syndrome. Monash University. Accessed February 7, 2025. https://www.monashfodmap.com/about-fodmap-and-ibs/

This randomized controlled trial investigated the effectiveness of linaclotide compared to placebo in reducing abdominal symptoms (bloating, discomfort, pain) in IBS-C patients using a patient-reported outcome tool (DIBSS-C). The study involved 614 patients across 78 U.S. centers, demonstrating that linaclotide significantly improved abdominal symptoms compared to placebo, with greater reductions in overall abdominal scores (-1.9 vs -1.2) and higher responder rates (40.5% vs 23.4%). Diarrhea-related discontinuation rates were low (1.6%), and symptom improvement persisted unless the medication was withdrawn.

The study supports linaclotide as a superior treatment option for IBS-C, particularly in addressing challenging abdominal symptoms not effectively relieved by osmotic laxatives. The authors emphasize realistic expectations—patients may require up to 12 weeks to see maximal benefit, and complete symptom resolution is uncommon. They recommend using linaclotide as part of a multimodal approach, combining it with dietary modifications, complementary therapies, or neuromodulators for optimal patient outcomes.

Reference: Deutsch J, Schoenfeld P. Treating All the Symptoms of IBS-C: Linaclotide Significantly Decreases Abdominal Pain, Bloating, and Discomfort. American College of Gastroenterology. Published January 13, 2022. Accessed April 14, 2025. https://gi.org/journals-publications/ebgi/treating-all-the-symptoms-of-ibs-c/

A survey of United States gastroenterologists explored their perceptions of dietary therapies for managing irritable bowel syndrome (IBS). The survey, which gathered responses from 1,562 gastroenterologists, found that nearly 60% of providers noted patients commonly associate food with gastrointestinal (GI) symptoms. Most patients with IBS use a trial-and-error approach to diet, with many trying lactose-free and gluten-free diets, though few independently follow a low FODMAP diet. Over half of the gastroenterologists recommend dietary therapy to more than 75% of their IBS patients, with the low FODMAP diet being the most suggested. However, only 21% of providers regularly refer patients to registered dietitians, and only 30% use GI dietitians.

The survey highlighted a general enthusiasm among gastroenterologists for using dietary therapies to manage IBS, particularly the low FODMAP diet, even though patients rarely try it independently. However, referral rates to dietitians, especially those with GI training, remain low. Female providers were found to be more likely to recommend dietary changes as the primary mode of therapy compared to their male counterparts. The results suggest that while dietary approaches are widely accepted, greater collaboration with specialized dietitians may be needed to optimize patient care.

Reference: Lenhart A, Ferch C, Shaw M, et al. Use of Dietary Management in Irritable Bowel Syndrome: Results of a Survey of Over 1500 United States Gastroenterologists. J Neurogastroenterol Motil. 2018 Jul 30;24(3):437-451. doi: 10.5056/jnm17116. PMID: 29886578; PMCID: PMC6034671.

This updated systematic review and meta-analysis aimed to assess the effectiveness of antidepressants and psychological therapies in treating irritable bowel syndrome (IBS). The analysis included 53 randomized controlled trials that compared antidepressants with placebo, and psychological therapies with control therapy or usual management. The results showed that antidepressants significantly reduced IBS symptoms, with a relative risk (RR) of 0.66 for symptoms not improving compared to placebo. Both tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) were found to be effective, although there was some heterogeneity among SSRIs trials. Psychological therapies, including cognitive behavioral therapy and hypnotherapy, also showed positive effects, with an RR of 0.69 for symptoms not improving, though there was significant variability between studies.

While both antidepressants and psychological therapies were found to be effective in reducing IBS symptoms, the quality of evidence for psychological therapies was limited, and treatment effects might have been overestimated due to issues with trial design, such as lack of blinding. The study concludes that antidepressants are an efficacious treatment for IBS, and psychological therapies can also be beneficial, but further high-quality trials are needed to confirm their true efficacy and optimize treatment approaches.

Reference: Ford AC, Lacy BE, Harris LA, et al. Effect of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-Analysis. Am J Gastroenterol. 2019 Jan;114(1):21-39. doi: 10.1038/s41395-018-0222-5. PMID: 30177784.

A multicenter, double-blind, placebo-controlled trial was conducted to determine if amitriptyline (10-30 mg nightly) is superior to placebo for improving irritable bowel syndrome (IBS) symptoms over 6 months in the primary care setting. The study included 463 patients who met the Rome IV criteria for IBS, with a baseline IBS-Symptom Severity Score (IBS-SSS) greater than 75. Patients were randomized to receive amitriptyline or a placebo, with the option to titrate the dose based on symptom improvement. The primary outcome was the change in IBS-SSS after 6 months, with a secondary outcome assessing global relief of IBS symptoms.

Results showed that amitriptyline significantly improved IBS symptoms, with the IBS-SSS score decreasing by an average of 27 points compared to 8 points for the placebo group (P = 0.008). Amitriptyline-treated patients were also more likely to report relief of IBS symptoms (odds ratio 1.78 for some relief, 1.88 for considerable/complete relief). Adverse events, primarily due to the drug’s anticholinergic effects, occurred more frequently in the amitriptyline group, with dry mouth, drowsiness, and blurred vision being the most common. Despite these side effects, amitriptyline was found to be effective in improving IBS symptoms in the primary care setting.

Reference: Schoenfeld P. Low-dose Tricyclic Antidepressants for Irritable Bowel Syndrome: Definitive Evidence of Benefit from ATLANTIS. American College of Gastroenterology. Published December 12, 2023. Accessed February 7, 2025. https://gi.org/journals-publications/ebgi/schoenfeld_dec2023/

Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are complex conditions involving a range of abdominal and bowel symptoms, including bloating, straining, abdominal pain, and hard stools. Effective symptom reporting is essential for diagnosis and individualized treatment, yet many patients delay seeking care due to embarrassment, dissatisfaction with prior healthcare encounters, or inadequate communication with providers. A strong clinician–patient relationship is critical to overcoming these barriers, enabling more accurate symptom reporting, improving health-related quality of life, and enhancing satisfaction with care. Patient-centered communication, shared understanding of symptom experiences, and education on symptom terminology are key components of successful long-term management.

Monitoring treatment response in CIC and IBS-C is equally important. Various patient-reported symptom scales—ranging from global assessments to detailed individual symptom tracking—can help clinicians evaluate treatment efficacy and refine care strategies. While global assessments offer a broad view of symptom burden, individualized symptom tools provide granular insights that guide more tailored treatment decisions. Including patients in discussions about their most bothersome symptoms, treatment expectations, and long-term care goals can improve adherence, outcomes, and overall satisfaction.

Reference: Kassebaum-Ladewski A, Poppers DM, Brenner DM. Effective Communication Strategies and Tools for Improving Treatment Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. Am J Gastroenterol. 2022 Apr 1;117(4S):S14-S20. doi: 10.14309/ajg.0000000000001686. PMID: 35354771.

Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are common gastrointestinal disorders, with CIC affecting 11.7% of the global population and IBS-C affecting 1.3%. Despite their prevalence, many individuals do not seek medical treatment, and those who do often turn to primary care after trying lifestyle changes and over-the-counter remedies. This review offers a comprehensive overview of treatment strategies to help healthcare providers improve long-term outcomes for patients with CIC and IBS-C.

Patients with CIC and IBS-C often start with over-the-counter remedies such as fiber and osmotic laxatives, but they may not achieve adequate relief and may be hesitant to use prescription medications due to concerns about dependency. Dietary fiber supplementation, gut microbial alterations, and treatments like probiotics, prebiotics, and osmotic laxatives are commonly recommended, though their efficacy may vary. The review emphasizes the importance of a clinical treatment algorithm and the need for patient education to ensure proper treatment selection. In some cases, combination therapy may be necessary to optimize outcomes. A comprehensive, patient-centered approach, considering both lifestyle factors and the potential for combination treatments, is crucial for managing these complex conditions effectively.

Reference: Brenner DM, Harris LA, Chang CH, et al. Real-World Treatment Strategies to Improve Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. Am J Gastroenterol. 2022 Apr 1;117(4S):S21-S26. doi: 10.14309/ajg.0000000000001709. PMID: 35354772.

This large, multicenter psychometric validation study assessed the reliability and validity of an experience sampling method-based patient-reported outcome measure (ESM-PROM) for real-time gastrointestinal symptom monitoring in patients with irritable bowel syndrome (IBS). Across 230 participants in three European countries, the ESM-PROM showed strong concurrent validity with end-of-day diaries and moderate correlations with end-of-week questionnaires. It also demonstrated good internal consistency—particularly in core IBS symptom domains—and excellent test-retest reliability. Unlike retrospective reports, which tend to inflate symptom severity due to recall bias, ESM provided a more accurate and ecologically valid representation of patients’ daily symptom experiences, reducing peak reporting bias and capturing moment-to-moment variability.

The ESM-PROM enables nuanced analysis of symptom patterns, triggers, and comorbid psychological and physical states in real-world settings, making it a powerful tool for personalized care and treatment evaluation. Despite its time demands and technical considerations, compliance was high, and the method showed minimal evidence of reactivity or survey fatigue. This tool has the potential to enhance clinical decision-making, self-management, and research into IBS pathophysiology and treatment efficacy. However, future research is needed to confirm its responsiveness to treatment interventions and to define its optimal use in various clinical and research scenarios.

Reference: Bosman M, Vork L, Jonkers D, et al. Results From a Psychometric Validation Study: Patients With Irritable Bowel Syndrome Report Higher Symptom Burden Using End-of-Day Vs Real-Time Assessment. Am J Gastroenterol. 2025 May 1;120(5):1098-1107. doi: 10.14309/ajg.0000000000003091. Epub 2024 Sep 23. PMID: 39311432; PMCID: PMC12043265.

Accurate diagnosis of constipation-predominant irritable bowel syndrome (IBS-C) can be challenging due to symptom subjectivity and overlapping etiologies such as functional, structural, metabolic, and medication-related causes. Misinterpretation of symptoms and self-medication with over-the-counter laxatives may mask underlying conditions, delay appropriate treatment, and increase the risk of mismanagement. A thorough, systematic clinical approach—including detailed history-taking, use of validated criteria, and appropriate diagnostic testing—is essential to differentiate functional constipation from secondary causes and guide effective treatment.

In response to the limitations of conventional treatments, herbal remedies have garnered increasing attention for their potential to alleviate IBS-C symptoms. This systematic review identified and evaluated nine studies on various herbal interventions, including padma lax, Chinese herbal medicine, Persian herbal syrup, and others like kiwifruit and geraniol. While some demonstrated statistically significant improvements in bowel habits, symptom severity, and quality of life, issues such as small sample sizes, lack of standardization, and insufficient regulatory oversight remain major concerns. Overall, the findings suggest that herbal therapies may offer complementary symptom relief in IBS-C, but high-quality, large-scale trials are urgently needed to validate their efficacy and safety and inform clinical practice.

Reference: Chiarioni G, Popa SL, Ismaiel A, et al. Herbal Remedies for Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review of Randomized Controlled Trials. Nutrients. 2023 Sep 29;15(19):4216. doi: 10.3390/nu15194216. PMID: 37836500; PMCID: PMC10574070.