Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study

Jingyi Hu; Jin Ding; Xia Li; Jun Li; Tingting Zheng; Lingxiang Xie; Chenyu Li; Yingxin Tang; Keyu Guo; Juan Huang; Shanshan Liu; Jianru Yan; Weijun Peng; Can Hou; Li Wen; Aimin Xu; Zhiguang Zhou; Yang Xiao

doi:10.1016/j.eclinm.2023.102132

Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study

EClinicalMedicine. 2023 Aug 3:62:102132. doi: 10.1016/j.eclinm.2023.102132. eCollection 2023 Aug.

Authors

Jingyi Hu¹, Jin Ding¹, Xia Li¹, Jun Li^{2

3}, Tingting Zheng², Lingxiang Xie¹, Chenyu Li¹, Yingxin Tang¹, Keyu Guo¹, Juan Huang¹, Shanshan Liu¹, Jianru Yan⁴, Weijun Peng⁵, Can Hou¹, Li Wen⁶, Aimin Xu^{7

8

9}, Zhiguang Zhou¹, Yang Xiao¹

Affiliations

¹ National Clinical Research Centre for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
² Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, China.
³ School of Data Science, City University of Hong Kong, Hong Kong, China.
⁴ Department of Endocrinology, The First People's Hospital of Pingjiang, Pingjiang, Hunan, China.
⁵ Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital of Central South University, Changsha, China.
⁶ Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
⁷ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
⁸ Department of Medicine, The University of Hong Kong, Hong Kong, China.
⁹ Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.

Abstract

Background: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs).

Methods: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728).

Findings: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs.

Interpretation: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond.

Funding: National Key Research and Development Program of China, the National Natural Science Foundation of China.

Keywords: Adult-onset diabetes; Diagnosis; Gut microbiota; Metabolites; Type 1 diabetes; Type 2 diabetes.

Associated data

ClinicalTrials.gov/NCT05252728

Abstract

Associated data

Grants and funding