Enhanced trimethylamine metabolism and gut dysbiosis in type 2 diabetes mellitus with microalbumin

Lixia Huo; Hui Li; Ming Zhu; Yang Liu; Lingyan Ren; Jia Hu; Xiaoyi Wang

doi:10.3389/fendo.2023.1257457

Enhanced trimethylamine metabolism and gut dysbiosis in type 2 diabetes mellitus with microalbumin

Front Endocrinol (Lausanne). 2023 Nov 20:14:1257457. doi: 10.3389/fendo.2023.1257457. eCollection 2023.

Authors

Lixia Huo¹, Hui Li², Ming Zhu³, Yang Liu¹, Lingyan Ren³, Jia Hu⁴, Xiaoyi Wang³

Affiliations

¹ Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital, Huzhou, Zhejiang, China.
² Department of Environmental and Occupational Health, Center for Disease Control and Prevention, Huzhou, Zhejiang, China.
³ Department of Nephrology, The First Affiliated Hospital of Huzhou University, The First People's Hospital, Huzhou, Zhejiang, China.
⁴ Department of Endocrinology, The First Affiliated Hospital of Huzhou University, The First People's Hospital, Huzhou, Zhejiang, China.

Abstract

Background: Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD).

Methods: This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively.

Results: The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, [Eubacterium]_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups.

Conclusion: The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.

Keywords: gut microbiota; trimethylamine; trimethylamine-n-oxide; type 2 diabetes mellitus with microalbuminuria; urinary albumin creatinine ratio.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacteria / genetics
Bacteria / metabolism
Diabetes Mellitus, Type 2* / complications
Dysbiosis* / complications
Gastrointestinal Microbiome*
Humans
Methylamines

Substances

Methylamines
trimethylamine
trimethyloxamine

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Zhejiang Basic Public Welfare Research Project (No. LGD21H050001); Zhejiang Medical and Health Technology Project (No. 2021KY1093, No. 2020KY310, No. 2022KY1224); and Huzhou Municipal Science and Technology Bureau Public Welfare Application Research Project (No. 2020GZ40).