Agarwal Samagra, Goswami Pooja, Poudel Shekhar, Gunjan Deepak, Singh Namrata, Yadav Rajni, Kumar Umesh, Pandey Gaurav, Saraya Anoop
Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Pancreatology. 2023 Jan;23(1):9-17. doi: 10.1016/j.pan.2022.11.011. Epub 2022 Nov 29.
The role of intestinal-barrier in acute pancreatitis(AP) is poorly understood. We aimed to assess structural and functional changes in the intestinal-barrier in patients with early AP (time from onset<2 weeks) and the effect of enteral nutrition on them.
In this prospective observational study, patients with early AP not on enteral nutrition were compared with controls for baseline intestinal-permeability(lactulose: mannitol ratio(L:M)), endotoxinemia(serum IgM/IgG anti-endotoxin antibodies), bacterial-translocation(serum bacterial 16S rRNA) and duodenal epithelial tight-junction structure by immunohistochemistry(IHC) for tight-junction proteins(claudin-2,-3,-4, zonula occludens-1(ZO1), junctional adhesion molecule(JAM) and occludin) and electron microscopy. These parameters were reassessed after 2 weeks enteral feeding in a AP patients subset.
96 patients with AP(age: 38.0 ± 14.5 years; etiology: biliary[46.8%]/alcohol[39.6%]; severe:53.2%, mortality:11.4%) and 40 matched controls were recruited. Patients with AP had higher baseline intestinal permeability(median L:M 0.176(IQR 0.073-0.376) vs 0.049(0.024-0.075) in controls; p < 0.001) and more frequent bacteraemia(positive bacterial 16S rRNA in 24/48 AP vs 0/21 controls; p < 0.001) with trend towards higher serum endotoxinemia(median IgG anti-endotoxin 78(51.2-171.6) GMU/ml vs 51.2(26.16-79.2) in controls; p = 0.061). Claudin-2, claudin-3, ZO1 were downregulated in both duodenal crypts and villi while claudin-4 and JAM were downregulated in duodenal villi and crypts respectively. 22 AP patients reassessed after initiation of enteral nutrition showed trend towards improving intestinal permeability, serum endotoxinemia and bacteraemia, with significant improvement in claudin-2,-3 in duodenal villi.
Patients with AP have significant disturbances in intestinal barrier structure and function in first 2 weeks from onset that persist despite institution of enteral nutrition.
肠道屏障在急性胰腺炎（AP）中的作用尚未完全明确。我们旨在评估早期AP患者（发病时间<2周）肠道屏障的结构和功能变化，以及肠内营养对其的影响。
在这项前瞻性观察研究中，将未接受肠内营养的早期AP患者与对照组在基线时进行肠道通透性（乳果糖：甘露醇比率[L:M]）、内毒素血症（血清IgM/IgG抗内毒素抗体）、细菌移位（血清细菌16S rRNA）比较，并通过免疫组织化学（IHC）检测十二指肠上皮紧密连接结构（紧密连接蛋白claudin-2、-3、-4、闭锁小带蛋白1[ZO1]、连接粘附分子[JAM]和闭合蛋白）以及电子显微镜观察。在一部分AP患者亚组中，于肠内喂养2周后重新评估这些参数。
招募了96例AP患者（年龄：38.0±14.5岁；病因：胆源性[46.8%]/酒精性[39.6%]；重症：53.2%，死亡率：11.4%）和40例匹配的对照组。AP患者基线时肠道通透性更高（中位数L:M为0.176[四分位间距0.073 - 0.376]，而对照组为0.049[0.024 - 0.075]；p<0.001），菌血症更常见（48例AP患者中有24例细菌16S rRNA阳性，而21例对照组中为0例；p<0.001），血清内毒素血症有升高趋势（中位数IgG抗内毒素为78[51.2 - 171.6]GMU/ml，对照组为51.2[26.16 - 79.2]；p = 0.061）。Claudin-2、claudin-3、ZO1在十二指肠隐窝和绒毛中均下调，而claudin-4和JAM分别在十二指肠绒毛和隐窝中下调。22例开始肠内营养后重新评估的AP患者显示肠道通透性、血清内毒素血症和菌血症有改善趋势，十二指肠绒毛中claudin-2、-3有显著改善。
AP患者在发病后的前2周肠道屏障结构和功能存在明显紊乱，尽管给予肠内营养，这种紊乱仍然持续存在。
