Zhang Chen-Yang, Peng Xin-Xin, Shao Hao-Qing, Li Xiao-Ya, Wu Yi, Tan Zhou-Jin
College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.
Hunan Key Laboratory of Traditional Chinese Medicine (TCM) Prescription and Syndromes Translational Medicine, Changsha, China.
Front Microbiol. 2021 Feb 23;12:626691. doi: 10.3389/fmicb.2021.626691. eCollection 2021.
Repeated stress-related diarrhea is a kind of functional bowel disorders (FBDs) that are mainly stemming from dysregulation of the microbiota-gut-brain axis mediated by a complex interplay of 5-hydroxytryptophan (5-HT). Intestinal content and intestinal mucosa microbiota belong to two different community systems, and the role of the two microbiota community systems in repeated stress-related diarrhea remains largely unknown. In order to ascertain the difference in composition and the potential function between intestinal content and intestinal mucosa microbiota response on repeated stress-related diarrhea, we collected intestinal contents and mucosa of mice with repeated stress-related diarrhea for 16S rRNA PacBio SMRT gene full-length sequencing, and with the digital modeling method of bacterial species abundance, the correlations among the two microbiota community systems and serum 5-HT concentration were analyzed. We found that the microbiotal composition differences both in intestinal contents and mucosa were consistent throughout all the phylogenetic ranks, with an increasing level of resolution. Compared with intestinal content microbiota, the diversity and composition of microbiota colonized in intestinal mucosa are more sensitive to repeated stress-related diarrhea. The PICRUSt2 of metagenomic function analysis found that repeated stress-related diarrhea is more likely to perturb the intestinal mucosa microbiota metagenomic functions involved in the neural response. We further found that the mucosal microbiota-based relative abundance model was more predictive on serum 5-HT concentration with the methods of machine-learning model established and multivariate dimensionality reduction ( = 0.876). These findings suggest that the intestinal mucosa microbiota might serve as a novel potential prediction model for the serum 5-HT concentration involvement in the repeated stress-related diarrhea, in addition to focusing on its mechanism in the gastrointestinal dysfunction.
反复应激相关腹泻是一种功能性胃肠疾病（FBDs），主要源于由5-羟色氨酸（5-HT）复杂相互作用介导的微生物群-肠-脑轴失调。肠内容物微生物群和肠黏膜微生物群属于两个不同的群落系统，这两个微生物群落系统在反复应激相关腹泻中的作用仍 largely unknown。为了确定肠内容物和肠黏膜微生物群在反复应激相关腹泻反应中的组成差异和潜在功能，我们收集了反复应激相关腹泻小鼠的肠内容物和黏膜进行16S rRNA PacBio SMRT基因全长测序，并采用细菌物种丰度的数字建模方法，分析了两个微生物群落系统与血清5-HT浓度之间的相关性。我们发现，在所有系统发育等级中，肠内容物和黏膜中的微生物组成差异都是一致的，分辨率水平不断提高。与肠内容物微生物群相比，定殖于肠黏膜的微生物群的多样性和组成对反复应激相关腹泻更为敏感。宏基因组功能分析的PICRUSt2发现，反复应激相关腹泻更有可能扰乱参与神经反应的肠黏膜微生物群宏基因组功能。我们进一步发现，通过建立机器学习模型和多变量降维方法，基于黏膜微生物群的相对丰度模型对血清5-HT浓度的预测性更强（ = 0.876）。这些发现表明，除了关注其在胃肠功能障碍中的机制外，肠黏膜微生物群可能作为血清5-HT浓度参与反复应激相关腹泻的一种新的潜在预测模型。
