G. Oppenheimer Center for Neurobiology of Stress & Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA CHS 42-210, MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.
UCLA Department of Integrative Biology and Physiology, Los Angeles, USA.
Microbiome. 2019 Mar 21;7(1):45. doi: 10.1186/s40168-019-0656-z.
BACKGROUND AND AIMS: Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. METHODS: We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. RESULTS: We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. CONCLUSIONS: In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.
背景与目的：来自临床前和临床研究的证据表明，大脑、肠道和微生物群之间的相互作用可能会影响肠易激综合征（IBS）的病理生理学。由于 IBS 患者存在中枢和外周 5-羟色胺能信号通路的紊乱，我们探索了这样一种假设，即梭菌目（Clostridiales）的调节 5-羟色胺的微生物丰度与躯体感觉脑区的功能连接和胃肠道（GI）感觉运动功能相关。 方法：我们于 2011 年至 2013 年在瑞典的一家二级/三级保健门诊对 65 例 IBS 患者和 21 例健康个体（对照组）进行了前瞻性研究。研究参与者在一个月内接受了功能脑成像、直肠球囊扩张、营养和乳果糖挑战试验以及肛口传输时间评估。他们还提交了粪便样本，这些样本通过 16S 核糖体 RNA 基因测序进行了分析。基于图论的三分网络分析用于研究梭菌目细菌之间的相互作用、躯体感觉网络中脑区的连接和 GI 感觉运动功能。 结果：我们发现，在对照组的粪便样本中，GI 感觉运动功能与肠道微生物之间存在关联，但在 IBS 患者的粪便样本中不存在这种关联。对照组和 IBS 患者之间最大的差异存在于 Lachnospiraceae incertae sedis、Clostridium XIVa 和 Coprococcus 亚网络中。我们发现，皮质下（丘脑、尾状核和壳核）和皮质（初级和次级躯体感觉皮质）区域的连接参与了这些网络之间相互作用的介导。 结论：在 IBS 患者和对照组患者的比较中，我们观察到 IBS 患者大脑、肠道和肠道微生物代谢物之间的相互作用出现紊乱，这些紊乱主要涉及皮质下区域，但也涉及大脑的皮质区域。这些紊乱可能导致 IBS 患者疼痛感知改变，并可能通过肠道 5-羟色胺能系统的微生物调节来介导。
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