Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.
Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.
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DOI：
10.1371/journal.pone.0175626
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Nakajima A
中科院分区：
文献类型：
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作者：
Kato T;Honda Y;Kurita Y;Iwasaki A;Sato T;Kessoku T;Uchiyama S;Ogawa Y;Ohkubo H;Higurashi T;Yamanaka T;Usuda H;Wada K;Nakajima A
小肠黏膜的屏障功能可防止有害病原体进入人体。这种屏障功能的破坏会增加肠道通透性。据推测，这不仅会诱发胃肠道疾病，包括炎症性肠病和肠易激综合征，还会诱发其他多种疾病，包括过敏、糖尿病、肝脏疾病和胶原病，这些疾病都与所谓的“肠漏综合征”有关。因此，一种预防肠漏综合征的方法将具有重大的临床价值。然而，到目前为止，还没有药物被证明能改善人类肠道通透性紊乱。因此，我们研究了一种用于治疗慢性便秘的药物——鲁比前列酮，是否对这一目的有效。
健康男性志愿者接受鲁比前列酮（24μg/天）治疗28天。在给予双氯芬酸后，通过测量乳果糖 - 甘露醇比值（LMR）来评估肠道通透性，并与未治疗组进行比较。检查总共进行三次，即在给予双氯芬酸前的基线水平以及鲁比前列酮治疗14天和28天后。同时也在相同时间点评估血液内毒素活性。
最终对28名受试者（鲁比前列酮组14名，未治疗组14名）进行了分析。治疗28天后，鲁比前列酮组的LMR显著低于未治疗组（分别为0.017对0.028；95%置信区间，−0.022 - −0.0001；p = 0.049）。鲁比前列酮组和未治疗组的血液内毒素活性随时间几乎没有变化，并且在任何检查时间点都没有显著差异。
这项研究首次报道了在人类中使用一种现有药物改善肠漏的情况。结果表明鲁比前列酮可能预防和改善“肠漏综合征”。然而，需要一项关键试验来证实我们的发现。
The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called “leaky gut syndrome.” As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, −0.022–−0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate “leaky gut syndrome”. However, a pivotal trial is needed to confirm our finding.