دورية أكاديمية
A242 STOOL FROM IBS-D PATIENT WITH A HISTORY OF A DYSBIOTIC AND NON-DYSBIOTIC ONSET MODULATE NEURONAL EXCITABILITY VIA DIFFERENT MECHANISMS
| العنوان: | A242 STOOL FROM IBS-D PATIENT WITH A HISTORY OF A DYSBIOTIC AND NON-DYSBIOTIC ONSET MODULATE NEURONAL EXCITABILITY VIA DIFFERENT MECHANISMS |
|---|---|
| المؤلفون: | Jiménez-Vargas, N N, Guzman Rodriguez, M, Yu, Y, Neary, E, Lomax, A E, Reed, D E, Vanner, S |
| المصدر: | Journal of the Canadian Association of Gastroenterology ; volume 5, issue Supplement_1, page 134-135 ; ISSN 2515-2084 2515-2092 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| الوصف: | Background We have shown that Irritable Bowel Syndrome diarrhea-predominant (IBS-D) patients with a history of a dysbiotic-like onset have distinct stool metabolomic profiles versus those with a non-dysbiotic-like onset. IBS stool supernatants can sensitize mouse colonic afferent nerves via both histamine and proteases. However, it is unknown if stool supernatants from the two IBS-D subgroups modulate the excitability of nociceptive neurons via different neuroactive mediators Aims To evaluate whether there are differences in neuroactive mediators within stool supernatants from subgroups of IBS-D patients that can modulate the excitability of nociceptive neurons. Methods Stool samples from healthy control (HC) (N=5) and IBS-D patients with a dysbiotic (N=7) or non-dysbiotic-like (N=7) onset, was homogenized with Krebs solution and filtered. Proteolytic activity was assessed using casein as a substrate with and without protease inhibitors. Histamine was quantified by ELISA. DRG neurons from C57BL/6 mice were incubated overnight or acutely (30 min) with stool supernatants. Some neurons were pre-incubated with PAR2 (GB83, 10 μM) or H1R (pyrilamine, 1μM) antagonists prior to supernatant incubation. Changes in neuronal excitability were assessed with perforated patch-clamp by measuring the rheobase (current that elicits an action potential). Results Proteolytic activity in dysbiotic-like (57.9 U/μg, p<0.05) but not non-dysbiotic like (37.4 U/μg) stool supernatant was increased compared to HC (25.2 U/μg). Serine inhibitor decreased proteolytic activity of dysbiotic (46.6%, p<0.05) and non-dysbiotic (34.2%, p<0.01) supernatant whereas cysteine, aspartic and metalloproteases inhibitors had no effect. Histamine was increased 78% (p<0.05) in IBS-D compared to HC. No differences in proteolytic activity and histamine concentration between IBS-D subtypes were found. In patch-clamp recordings, overnight incubation with dysbiotic (19%, p<0.05) and non-dysbiotic (22%, p< 0.01) ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/jcag/gwab049.241 |
| الإتاحة: | https://doi.org/10.1093/jcag/gwab049.241Test https://academic.oup.com/jcag/article-pdf/5/Supplement_1/134/42563623/gwab049.241.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.1D87DD8C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jcag/gwab049.241 |
|---|