Makizaki Yutaka, Kishimoto Mana, Tanaka Yoshiki, Ohno Hiroshi
R&D Center, Biofermin Pharmaceutical Co., Ltd., 7-3-4 Higashi-machi, Ibukidai, Nishi-ku, Kobe, Hyogo 651-2242, Japan.
Biosci Microbiota Food Health. 2024;43(3):234-240. doi: 10.12938/bmfh.2023-084. Epub 2024 Mar 15.
Constipation is strongly associated with the deterioration of quality of life (QOL), and patients with constipation desire clear spontaneous defecation without the feeling of incomplete evacuation, rather than improved defecation frequency. The use of common osmotic or stimulant laxatives has not been shown to lead to a satisfactory improvement of bowel movements. In addition, softening of stools by increasing their water content has been reported to increase the frequency of spontaneous defecation and improve hard stools, straining during defecation, and abdominal symptoms, such as abdominal bloating, thereby leading to improvement of QOL deterioration caused by constipation. Thus, the present study screened bacterial strains using intestinal epithelial T84 cells, aiming to identify one that activates chloride channels involved in water secretion into the intestinal tract. As a result, the conditioned medium of CLA8013 was found to induce ion transport. Also, this effect was suppressed by cystic fibrosis transmembrane conductance regulator (CFTR) (inh)-172, a CFTR chloride channel inhibitor. Furthermore, both live and heat-killed CLA8013 similarly induced ion transport, suggesting that bacterial cell components are responsible for the effect. In addition, the administration of heat-killed CLA8013 to loperamide-induced constipation rats resulted in an increase in fecal water content and promoted defecation. These results suggest that the active components in CLA8013 act on CFTR chloride channels in the intestinal tract, promote water secretion into the intestinal tract, and soften stools, thereby promoting bowel movements.
便秘与生活质量(QOL)的恶化密切相关,便秘患者渴望自然排便顺畅,无排便不尽感,而非排便频率的改善。使用常见的渗透性或刺激性泻药尚未显示能使排便得到令人满意的改善。此外,据报道,通过增加粪便含水量来软化粪便可增加自然排便频率,并改善硬便、排便时用力以及腹胀等腹部症状,从而改善便秘导致的生活质量恶化。因此,本研究使用肠上皮T84细胞筛选细菌菌株,旨在鉴定一种能激活参与肠道水分分泌的氯离子通道的菌株。结果发现,CLA8013的条件培养基可诱导离子转运。此外,这种作用被囊性纤维化跨膜传导调节因子(CFTR)(inh)-172(一种CFTR氯离子通道抑制剂)所抑制。此外,活的和热灭活的CLA8013均同样诱导离子转运,这表明细菌细胞成分是产生该作用的原因。此外,给洛哌丁胺诱导的便秘大鼠施用热灭活的CLA8013会导致粪便含水量增加并促进排便。这些结果表明,CLA8013中的活性成分作用于肠道中的CFTR氯离子通道,促进肠道水分分泌并软化粪便,从而促进排便。