Smart capsule for targeted proximal colon microbiome sampling.
Smart capsule for targeted proximal colon microbiome sampling.
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DOI：
10.1016/j.actbio.2022.09.050
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发表时间：
2022-12
影响因子：
9.7
通讯作者：
Rahimi R
中科院分区：
文献类型：
--
作者：
Nejati S;Wang J;Sedaghat S;Balog NK;Long AM;Rivera UH;Kasi V;Park K;Johnson JS;Verma MS;Rahimi R
胃肠道（GI），特别是结肠区域，拥有高度多样化的微生物群落，在宿主身体的代谢，生理，营养和免疫功能中起着重要作用。越来越多的证据表明，这些微生物群落的改变是发展各种代谢疾病的关键步骤，包括肥胖、炎症性肠病（IBD）和结直肠癌。然而，仍然缺乏对微生物群和饮食之间的相互关系以及化学预防策略的有效性的明确理解，包括前体和益生菌制剂在改变结肠微生物群和预防消化系统疾病中的作用。用于评估这些微生物群-饮食相互作用的现有方法通常基于从粪便收集的样品或内窥镜检查技术，其不能提供关于肠道微生物群的空间变化的信息或被认为是侵入性程序。为了满足这一需求，我们开发了一种无电子智能胶囊，可以对胃肠道近端结肠区域内的肠道微生物组进行特定部位的采样。该3D打印设备容纳了一种结合在柔性聚二甲基硅氧烷（PDMS）盘上的高吸水性水凝胶，该盘作为环境，通过快速膨胀收集肠腔及其微生物组中的流体，并提供必要的机械驱动以在采样完成后关闭胶囊。靶向结肠采样通过用双层pH敏感肠溶包衣涂覆胶囊上的采样孔来实现，其延迟管腔中的流体进入胶囊直到其到达胃肠道的近端结肠。为了确定适当的pH响应双层包衣和加工条件，在模拟胃肠道的不同pH条件下进行了一系列系统的溶出表征。使用具有混合细菌培养物的真实体外胃肠道模型和以猪作为动物模型的体内模型，验证了具有优化设计的智能胶囊的有效靶向微生物采样性能和保存。体外和体内研究中的16 sRNA和WideSeq分析结果表明，回收胶囊内采样的细菌种群与目标采样区域（近端结肠）内的细菌种群密切匹配。在本文中，设想这种智能采样胶囊技术将为胃肠病学研究和临床应用提供新的途径，包括饮食-宿主-微生物组关系，专注于人类GI功能和健康。
The gastrointestinal (GI) tract, particularly the colon region, holds a highly diverse microbial community that plays an important role in the metabolism, physiology, nutrition, and immune function of the host body. Accumulating evidence has revealed that alteration in these microbial communities is the pivotal step in developing various metabolic diseases, including obesity, inflammatory bowel disease (IBD), and colorectal cancer. However, there is still a lack of clear understanding of the interrelationship between microbiota and diet as well as the effectiveness of chemoprevention strategies, including pre and probiotic agents in modifying the colonic microbiota and preventing digestive diseases. Existing methods for assessing these microbiota-diet interactions are often based on samples collected from the feces or endoscopy techniques which are incapable of providing information on spatial variations of the gut microbiota or are considered invasive procedures. To address this need, here we have developed an electronic-free smart capsule that enables site-specific sampling of the gut microbiome within the proximal colon region of the GI tract. The 3D printed device houses a superabsorbent hydrogel bonded onto a flexible polydimethylsiloxane (PDMS) disk that serves as a milieu to collect the fluid in the gut lumen and its microbiome by rapid swelling and providing the necessary mechanical actuation to close the capsule after the sampling is completed. The targeted colonic sampling is achieved by coating the sampling aperture on the capsule with a double-layer pH-sensitive enteric coating, which delays fluid in the lumen from entering the capsule until it reaches the proximal colon of the GI tract. To identify the appropriate pH-responsive double-layer coating and processing condition, a series of systematic dissolution characterizations in different pH conditions that mimicked the GI tract was conducted. The effective targeted microbial sampling performance and preservation of the smart capsule with the optimized design were validated using both realistic in vitro GI tract models with mixed bacteria cultures and in vivo with pigs as an animal model. The results from 16sRNA and WideSeq analysis in both in vitro and in vivo studies showed that the bacterial population sampled within the retrieved capsule closely matched the bacterial population within the targeted sampling region (proximal colon). Herein, it is envisioned that such smart sampling capsule technology will provide new avenues for gastroenterological research and clinical applications, including diet-host-microbiome relationships, focused on human GI function and health.
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