PMID- 38079576
OWN - NLM
STAT- MEDLINE
DCOM- 20240222
LR  - 20240224
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 73
IP  - 3
DP  - 2024 Mar 1
TI  - Multiomics Analyses With Stool-Type Stratification in Patient Cohorts and Blautia 
      Identification as a Potential Bacterial Modulator in Type 2 Diabetes Mellitus.
PG  - 511-527
LID - 10.2337/db23-0447 [doi]
AB  - Heterogeneity in host and gut microbiota hampers microbial precision intervention 
      of type 2 diabetes mellitus (T2DM). Here, we investigated novel features for 
      patient stratification and bacterial modulators for intervention, using 
      cross-sectional patient cohorts and animal experiments. We collected stool, 
      blood, and urine samples from 103 patients with recent-onset T2DM and 25 healthy 
      control subjects (HCs), performed gut microbial composition and metabolite 
      profiling, and combined it with host transcriptome, metabolome, cytokine, and 
      clinical data. Stool type (dry or loose stool), a feature of the stool 
      microenvironment recently explored in microbiome studies, was used for 
      stratification of patients with T2DM as it explained most of the variation in the 
      multiomics data set 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 with 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 multiomics data set. 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.
CI  - (c) 2024 by the American Diabetes Association.
FAU - Guo, Qian
AU  - Guo Q
AD  - Department of Biomedical Engineering, College of Future Technology, and Center 
      for Quantitative Biology, Peking University, Beijing, China.
FAU - Gao, Zezheng
AU  - Gao Z
AD  - Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese 
      Medical Sciences, Beijing.
FAU - Zhao, Linhua
AU  - Zhao L
AUID- ORCID: 0000-0002-0362-7365
AD  - Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese 
      Medical Sciences, Beijing.
FAU - Wang, Han
AU  - Wang H
AD  - Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese 
      Medical Sciences, Beijing.
FAU - Luo, Zhen
AU  - Luo Z
AD  - Infinitus (China) Company Ltd., Jiangmen, China.
FAU - Vandeputte, Doris
AU  - Vandeputte D
AD  - Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY.
AD  - Center for Microbiology, VIB-KU Leuven, Leuven, Belgium.
FAU - He, Lisha
AU  - He L
AD  - Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Li, Mo
AU  - Li M
AD  - Department of Biomedical Engineering, College of Future Technology, and Center 
      for Quantitative Biology, Peking University, Beijing, China.
FAU - Di, Sha
AU  - Di S
AD  - Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese 
      Medical Sciences, Beijing.
FAU - Liu, Yanwen
AU  - Liu Y
AD  - Department of Endocrinology, Zhengzhou Traditional Chinese Medicine Hospital, 
      Zhengzhou, China.
FAU - Hou, Jiaheng
AU  - Hou J
AD  - Department of Biomedical Engineering, College of Future Technology, and Center 
      for Quantitative Biology, Peking University, Beijing, China.
FAU - Jiang, Xiaoqing
AU  - Jiang X
AD  - Department of Biomedical Engineering, College of Future Technology, and Center 
      for Quantitative Biology, Peking University, Beijing, China.
FAU - Zhu, Huaiqiu
AU  - Zhu H
AUID- ORCID: 0000-0002-6376-218X
AD  - Department of Biomedical Engineering, College of Future Technology, and Center 
      for Quantitative Biology, Peking University, Beijing, China.
FAU - Tong, Xiaolin
AU  - Tong X
AUID- ORCID: 0000-0002-9873-4154
AD  - Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese 
      Medical Sciences, Beijing.
LA  - eng
GR  - ZYYCXTD-D-202001/Innovation Team and Talents Cultivation Program of National 
      Administration of Traditional Chinese Medicine/
GR  - 31671366/National Natural Science Foundation of China/
GR  - 2021YFC2300300/Research and Development Program of China/
PT  - Journal Article
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Cross-Sectional Studies
MH  - Multiomics
MH  - Feces/microbiology
MH  - Bacteria/genetics
PMC - PMC10882154
COIS- Duality of Interest. No potential conflicts of interest relevant to this article 
      were reported.
EDAT- 2023/12/11 18:42
MHDA- 2024/02/22 06:42
PMCR- 2023/12/11
CRDT- 2023/12/11 15:52
PHST- 2023/06/08 00:00 [received]
PHST- 2023/12/06 00:00 [accepted]
PHST- 2024/02/22 06:42 [medline]
PHST- 2023/12/11 18:42 [pubmed]
PHST- 2023/12/11 15:52 [entrez]
PHST- 2023/12/11 00:00 [pmc-release]
AID - 153967 [pii]
AID - 230447 [pii]
AID - 10.2337/db23-0447 [doi]
PST - ppublish
SO  - Diabetes. 2024 Mar 1;73(3):511-527. doi: 10.2337/db23-0447.