PDF(Pubmed)
Abstract：
BACKGROUND: Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated.
RESULTS: Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection.
CONCLUSIONS: For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.
RESULTS: Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection.
CONCLUSIONS: For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.
摘要：
背景：小儿慢性肠假性梗阻（PIPO）是一种罕见的疾病，其特征是症状和放射学体征提示肠梗阻，在没有管腔阻塞病变的情况下。这是由于推进运动极其严重的损害。肠内分泌系统（IES）与肠神经系统（ENS）共同通过不同的激素和生物活性信使/神经递质调节分泌运动功能。神经递质5-羟色胺（5-HT）（或5-羟色胺）与肠蠕动和分泌反射有关。肠道菌群及其与ENS的相互作用影响5-HT合成，释放,以及随后的5-羟色胺受体激活。迄今为止,PIPO中5-HT与肠道菌群之间的相互作用仍不清楚。本研究旨在评估粘膜相关微生物群(MAM)之间的相关性，肠道5-羟色胺相关基因在PIPO中的表达。为此,结肠活检，收集了7名PIPO患者的回肠和十二指肠，和7个年龄/性别匹配的健康对照。DNA提取后,通过细菌RNA16S的V3-V4区域的下一代测序（NGS）评估MAM，在IlluminaMiseq平台上.通过qPCR建立了与5-羟色胺能途径有关的基因（TPH1，SLC6A4，5-HTR3和5-HTR4）的表达，并评估了与MAM和PIPO临床参数的相关性。
结果：我们的结果显示，PIPO患者表现出具有不同组成和菌群失调的MAM，即生物多样性较低，联系较少，非协同关系较多的物种较少，与对照组相比。qPCR结果揭示了在PIPO患者中5-羟色胺相关的肠道基因表达的改变,与对照组相比。相关性分析不能揭示任何类型的联系。
结论：第一次，我们在PIPO患者中报道了与基础病理相关的特定MAM和改变的肠道5-羟色胺途径。5-羟色胺途径的可能功能障碍，可能与改变的微生物群有关或由其触发，可能导致PIPO患者运动障碍。我们的初步研究结果为针对PIPO患者的微生物群或5-羟色胺途径的新生物标志物和创新疗法提供了基础。
结果：我们的结果显示，PIPO患者表现出具有不同组成和菌群失调的MAM，即生物多样性较低，联系较少，非协同关系较多的物种较少，与对照组相比。qPCR结果揭示了在PIPO患者中5-羟色胺相关的肠道基因表达的改变,与对照组相比。相关性分析不能揭示任何类型的联系。
结论：第一次，我们在PIPO患者中报道了与基础病理相关的特定MAM和改变的肠道5-羟色胺途径。5-羟色胺途径的可能功能障碍，可能与改变的微生物群有关或由其触发，可能导致PIPO患者运动障碍。我们的初步研究结果为针对PIPO患者的微生物群或5-羟色胺途径的新生物标志物和创新疗法提供了基础。
