Department of Public Health and Infectious Diseases, Microbiology section, Sapienza University of Rome, Rome, Italy.
Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
BMC Microbiol. 2024 Feb 2;24(1):48. doi: 10.1186/s12866-024-03200-z.
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.
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.
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.
小儿慢性肠假性梗阻（PIPO）是一种罕见的疾病，其特征是存在提示肠梗阻的症状和影像学征象，但不存在管腔闭塞性病变。它是由推进运动的严重损伤引起的。肠内分泌系统（IES）与肠神经系统（ENS）一起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）（或血清素）与肠道蠕动和分泌反射有关。肠道微生物群及其与 ENS 的相互作用影响 5-HT 的合成、释放和随后的血清素受体激活。迄今为止，PIPO 中 5-HT 与肠道微生物群之间的相互作用仍不清楚。本研究旨在评估 PIPO 患者的黏膜相关微生物群（MAM）与肠道 5-羟色胺相关基因表达之间的相关性。为此，从 7 名 PIPO 患者和 7 名年龄/性别匹配的健康对照中采集了结肠、回肠和十二指肠的活检。提取 DNA 后，通过 Illumina Miseq 平台对细菌 RNA 16S 的 V3-V4 区进行下一代测序（NGS），评估 MAM。通过 qPCR 确定参与 5-羟色胺能途径的基因（TPH1、SLC6A4、5-HTR3 和 5-HTR4）的表达，并评估与 PIPO 的 MAM 和临床参数的相关性。
我们的结果表明，与对照组相比，PIPO 患者的 MAM 组成不同且存在失调，即生物多样性较低，与较少的连接物种较少，具有更多的非协同关系。与对照组相比，qPCR 结果显示 PIPO 患者肠道 5-羟色胺相关基因的表达发生改变。相关性分析未显示任何类型的联系。
我们首次在 PIPO 患者中报告了一种特定的 MAM，该 MAM与潜在的病理学有关，并且肠道 5-羟色胺途径发生改变。5-羟色胺途径的功能障碍可能与微生物群或由微生物群触发的改变有关，可能导致 PIPO 患者的运动功能障碍。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。
