341: Longitudinal QST Phenotyping Reveals Microbiome and Symptom Profiles in Irritable Bowel Syndrome

Topic: Clinical Science
Subtopic: Non-specific to any diagnosis, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics), Assessment and Measurement of Pain/Nociception, Pain in Special Populations

Background and Aims: Irritable bowel syndrome (IBS) is the most prevalent disorder of gut-brain interaction, characterized primarily by recurrent chronic abdominal pain, which severely impacts the quality of life and productivity of affected individuals, particularly in young adults (1-3). However, the clinical management of IBS pain remains challenging due to the lack of objective biomarkers and the inherent difficulties in measuring its complex, multifaceted pathophysiology (3-8). This study aimed to examine Quantitative Sensory Testing (QST) phenotypes over 12 weeks, along with phenotype-associated symptoms and gut microbiome signatures, in comparison with healthy controls (HC).

Methods: A longitudinal cohort study was designed. IBS-related symptoms were assessed using the Brief Pain Inventory and PROMIS® short forms at weeks 0, 6, and 12. QST was conducted to measure mechanical, thermal, and pressure pain thresholds. PCA and longitudinal k-means applied to cluster QST phenotypes. Participants' stool samples were collected throughout the study, and gut microbial composition was analyzed using 16S rRNA sequencing. Microbial profiles were compared across phenotypes and HC, including assessments of alpha diversity (Shannon, Chao1; Kruskal-Wallis), beta diversity (Bray-Curtis/Jaccard; PERMANOVA), and differential taxa (ANCOM-BC2). Functional potential was inferred using PICRUSt2 to predict KEGG pathways.

Results: Sixty-two IBS participants and 21 HCs (mean age 21.7±2.7 years) were included. Two QST phenotypes emerged: Cluster A (sensory thresholds similar to controls) and Cluster B (reduced sensitivity). Although pain levels were comparable between clusters, Cluster B reported higher anxiety and sleep disturbance (p<0.05) throughout the study. At baseline, Cluster A demonstrated greater alpha diversity (p<0.01) and enrichment of metabolic pathways linked to visceral hypersensitivity (methane, fructose, and pyruvate metabolism; FDR q<0.10), along with increased Desulfovibrio (FDR q<0.05). By week 12, 26 baseline microbial functional differences were attenuated and no longer statistically significant.

Conclusions: QST phenotypes reveal that participants with the same pain level can have different underlying mechanisms. Individuals exhibiting an increased dull somatic sensitivity (Cluster B) are likely to experience a top-down mechanism principally influenced by psychological pain triggers. In contrast, Cluster A, closer to HCs, may be influenced by bottom-up gut-metabolic pain triggers. This suggests that QST could help tailor treatment approaches: Cluster A individuals might respond better to gut-focused interventions such as a low-FODMAP diet, whereas Group B individuals might benefit more from mind-body therapies.

References: Reference:
1. Mayer EA, Ryu HJ, Bhatt RR. The neurobiology of irritable bowel syndrome. Mol Psychiatry. Apr 2023;28(4):1451–1465. doi:10.1038/s41380-023-01972-w
2. Huang KY, Wang FY, Lv M, Ma XX, Tang XD, Lv L. Irritable bowel syndrome: Epidemiology, overlap disorders, pathophysiology and treatment. World J Gastroenterol. Jul 14 2023;29(26):4120–4135. doi:10.3748/wjg.v29.i26.4120
3. Chen J, Barandouzi ZA, Lee J, et al. Psychosocial and Sensory Factors Contribute to Self-Reported Pain and Quality of Life in Young Adults with Irritable Bowel Syndrome. Pain Manag Nurs. Oct 2022;23(5):646–654. doi:10.1016/j.pmn.2021.12.004
4. Cong X, Perry M, Bernier KM, Young EE, Starkweather A. Effects of Self-Management Interventions in Patients With Irritable Bowel Syndrome: Systematic Review. West J Nurs Res. Nov 2018;40(11):1698–1720. doi:10.1177/0193945917727705
5. Black CJ, Ford AC. Best management of irritable bowel syndrome. Frontline Gastroenterol. 2021;12(4):303–315. doi:10.1136/flgastro-2019-101298
6. Orock A, Yuan T, Greenwood-Van Meerveld B. Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance. Front Pain Res (Lausanne). 2020;1:609292. doi:10.3389/fpain.2020.609292
7. Zhou Q, Verne GN. New insights into visceral hypersensitivity--clinical implications in IBS. Nat Rev Gastroenterol Hepatol. Jun 2011;8(6):349–55. doi:10.1038/nrgastro.2011.83
8. Chen; J, Zhang; Y, Barandouzi; ZA, et al. Somatosensory Profiles Differentiate Pain and Psychophysiological Symptoms Among Young Adults With Irritable Bowel Syndrome: A Cluster Analysis. . The Clinical journal of pain. 2022;38(7):492–501. doi:10.1097/AJP.0000000000001046

Presenting Author: Weizi Wu
Submitting Author: Xiaomei Cong

Senior Author: Xiaomei Cong

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Weizi Wu: PhD - Yale University School of Nursing
• Aolan Li: PhD - Yale University School of Nursing
• Leonel Rodriquez: MD - Yale University School of Medicine
• Angela Starkweather: PhD - Rodgers University School of Nursing
• Jie Chen: PhD - Florida State University School of Nursing
• Xiaomei Sophia Cong: PhD - Yale University School of Nursing