Patients with symptomatic uncomplicated diverticular disease have high fecal bile acid concentrations

Tsumugi Jono^1,2Yuki Kasai¹Takaomi Kessoku^1,3,4Michihiro Iwaki¹Kosuke Tanaka^1,4Takashi Kobayashi¹Kota Takahashi¹Kosuke Seita⁵Takayuki Kato⁵Eiji Sakai²Takeo Kurihashi⁶Machiko Nakatogawa⁷Shunsuke Oyamada⁸Seiji Futagami⁹KOK ANN GWEE¹⁰Atsushi Nakajima^1*Antonio Tursi¹¹

• ¹Graduate School of Medicine, Yokohama City University, Yokohama, Japan
• ²Yokohama Sakae Kyosai Hospital, Yokohama, Kanagawa, Japan
• ³Graduate School of Medicine, International University Health and Welfare, Narita, Japan
• ⁴Narita Hospital, International University of Health and Welfare (IUHW), Narita, Chiba, Japan
• ⁵International University of Health and Welfare Atami hospital, Atami, Japan
• ⁶Yokohama Clinic, Kanagawa Dental University, Yokohama, Kanagawa, Japan
• ⁷Namiki Koiso-Medical Clinic, Yokohama, Japan
• ⁸JORTC Data Center, Tokyo, Japan
• ⁹Nippon Medical School, Bunkyō, Tōkyō, Japan
• ¹⁰National University Hospital, Singapore, Singapore
• ¹¹Azienda Sanitaria Localedella Provincia di Barletta Andri Trani (ASL BT), Andria, Italy

Background and Aim: Symptomatic uncomplicated diverticular disease (SUDD) causes persistent pain and impairs patient quality of life; however, its pathogenesis remains unknown. This study investigated the relationship between SUDD and the inflammatory effects of intestinal bile acids (BAs).Methods: Five institutional cohorts with 361 total patients who received outpatient treatment for abdominal symptoms (from 2020-2022) were included in this prospective cohort study. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms-pain in the lower quadrant lasting >24 h-in patients with diverticulosis at the site of pain. Patients with diverticula were classified into SUDD and non-SUDD groups. The healthy control (HC) group comprised people with no history of medications and no evidence of colonic diverticula. Liquid chromatography-mass spectrometry determined the concentration of fecal BAs. Fecal calprotectin and blood endotoxin activity assay (EAA) levels were measured. Results: Total fecal BA concentrations did not differ between HC and non-SUDD patients; however, BA levels were significantly higher in patients with SUDD. Fecal calprotectin and blood EAA levels were significantly higher in the SUDD and non-SUDD groups than in the HC group, and in the SUDD group than in the non-SUDD group. Total BA was mildly positively correlated with fecal calprotectin and blood EAA. Conclusion: Fecal BA concentrations were significantly increased in patients with SUDD compared with patients without SUDD or healthy subjects, suggesting that fecal BAs might be involved in the pathogenesis of SUDD and that controlling fecal BA levels may be therapeutic for SUDD.