Abstract
Although most patients with type 2 diabetes mellitus (T2DM) and circadian rhythm disruption have poor blood glucose control, a fraction of patients with T2DM and circadian rhythm disruption who still have good blood glucose control. Previous studies have shown that individuals with circadian rhythm disruption are more prone to developing T2DM, and the occurrence of T2DM is associated with the gut microbiota. However, the role of gut microbiota in patients with T2DM and circadian rhythm disruption remains unclear. Stool samples were collected from 6 patients with poorly controlled type 2 diabetes mellitus (T2DM) and circadian rhythm disruption, as well as from 6 patients with well-controlled T2DM and circadian rhythm disruption. Metagenomic sequencing was performed on the stool samples. Compared to the well-controlled group, the abundance of Lactobacillus johnsonii(L. johnsonii ) was significantly decreased in the poorly controlled group. To investigate the effects of L. johnsonii supplementation on glucose and lipid metabolism, diabetic mice with circadian rhythm disruption were administered L. johnsonii and their metabolic indicators were measured. Metagenomic sequencing of the gut microbiota revealed a higher microbial diversity in the well blood glucose controlled type 2 diabetes combined with disrupted circadian rhythm group (W-T2D-RD). Additionally, a significant decrease in the abundance of L. johnsonii was observed in patients with poor blood glucose controlled type 2 diabetes combined with disrupted circadian rhythm group (P-T2D-RD) when compared to those with W-T2D-RD. Following supplementation of L. johnsonii to the mice in the type 2 diabetes mellitus rhythm disruption Lactobacillus johnsonii group (T2DM-RD-L), the fasting blood glucose levels and postprandial blood glucose levels were significantly reduced. Additionally, total cholesterol and low-density lipoprotein levels decreased, high-density lipoprotein levels increased in the T2DM-RD-L group. Lactobacillus johnsonii has a positive impact on both glucose and lipid metabolism in patients with type 2 diabetes mellitus and circadian rhythm disruption.
Data availability
Sequence data that support the findings of this study have been deposited in the National Center for Biotechnology Information with the primary accession code SUB14302900(PRJNA1087526). https://submit.ncbi.nlm.nih.gov/subs/sra/SUB14302900/overview.
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Funding
Funded by Science and Technology Project of Hebei Education Department (BJK2024152). Precision Medicine Project of Hebei Natural Science Foundation (H2025402021). Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No. [2020] No.23). Hebei Province Medical Science Research Project Plan for 2024 (20241988).
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Wang Defeng, Wang Zhen, and Yang Yan conceived and designed the project. Yang Yan, Shen Hongxia and Sun Li collected samples. Yang Yan, Shi Zhenhong, Mei Xianghui and Wu Na conducted animal experiments.Yang Yan wrote the manuscript. Wang Defeng and Wang Zhen reviewed and edited the manuscript. All authors made substantial contributions and approved the final version of the manuscript.
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The studies involving human participants were reviewed and approved by Ethics Committee of Hebei University of Engineering affiliated hospital. The patients/participants provided their written informed consent to participate in this study.This animal experiments was approved by the Institutional Animal Care and Use Committee of Hebei University of Engineering affiliated hospital (IACUC-Hebeu-2023-0006).
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Yan, Y., Zhen, W., Hongxia, S. et al. Impact of Lactobacillus johnsonii on glycemic control and lipid metabolism in type 2 diabetes with circadian disruption. Sci Rep (2026). https://doi.org/10.1038/s41598-025-94359-6
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DOI: https://doi.org/10.1038/s41598-025-94359-6