American Diabetes Association
Supplementary_materials_revised_cleancopy.pdf (3.37 MB)

Multi-omics analyses with stool-type stratification in patient cohorts and Blautia identification as a potential bacterial modulator in T2DM

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posted on 2023-12-11, 20:37 authored by Qian Guo, Zezheng Gao, Linhua Zhao, Han Wang, Zhen Luo, Doris Vandeputte, Lisha He, Mo Li, Sha Di, Yanwen Liu, Jiaheng Hou, Xiaoqing Jiang, Huaiqiu Zhu, Xiaolin Tong

Heterogeneity in host and gut microbiota hampers microbial precision intervention of type 2 diabetes mellitus (T2DM). Here, we investigate novel features for patient-stratification and bacterial modulators for intervention, using cross-sectional patient cohorts and animal experiments. We collected stool/blood/urine samples from 103 recent-onset T2DM patients and 25 healthy controls (HCs), performed gut microbial composition/metabolite profiling, and combined it with host-transcriptome/metabolome/cytokines and clinical data. Stool-type (dry/loose-stool), a feature of stool-microenvironment recently explored in microbiome studies, was used for T2DM patient-stratification as it explained most of the variation in multi-omics dataset among all clinical parameters in our covariate analysis. T2DM with dry-stool (DM-DS) and loose-stool (DM-LS) were clearly differentiated from HC and each other by LightGBM-models, optimal among multiple machine-learning models. Compared to DM-DS, DM-LS exhibited discordant gut microbial taxonomic and functional profiles, severe host metabolic disorder, and excessive insulin secretion. Further cross-measurement-association-analysis linked the differential microbial profiles, in particular Blautia abundances, to T2DM phenotypes in our stratified multi-omics dataset. Notably, oral supplementation of Blautia to T2DM mice induced inhibitory effects on lipid accumulation, weight gain, and blood-glucose elevation with simultaneous modulation of gut bacterial composition, revealing the therapeutic potential of Blautia. Our study highlights the clinical implications of stool-microenvironment stratification and Blautia supplementation in T2DM, offering promising prospects for microbial precision treatment of metabolic diseases.


This work was supported by the National Key Research and Development Program of China (2021YFC2300300), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202001) and the National Natural Science Foundation of China (81430097, 81973837, 32070667, 31671366, 32300078).


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