Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2022; 28(21): 2320-2333
Published online Jun 7, 2022. doi: 10.3748/wjg.v28.i21.2320
Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome
Sha-Sha Tang, Cheng-Hong Liang, Ya-Lei Liu, Wei Wei, Xin-Ru Deng, Xiao-Yang Shi, Li-Min Wang, Li-Jun Zhang, Hui-Juan Yuan
Sha-Sha Tang, Cheng-Hong Liang, Ya-Lei Liu, Wei Wei, Xin-Ru Deng, Xiao-Yang Shi, Li-Min Wang, Li-Jun Zhang, Hui-Juan Yuan, Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Author contributions: Tang SS designed the research and conducted microbiome analysis; Liu YL conducted the research except the microbiome analysis; Tang SS and Liang CH analyzed the microbiome data and wrote the paper; all other data were analyzed by Shi XY and Deng XR with oversight by Wei W; Zhang LJ and Wang LM were responsible for the data acquisition and input and proofreading of the manuscript; Tang SS and Yuan HJ had primary responsibility for the final content; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81970705; and Central Plains Thousand Talents Plan, No. 204200510026.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Henan Provincial People’s Hospital (IRB No. 2019-62).
Informed consent statement: All study participants provided informed written consent before the study enrollment.
Conflict-of-interest statement: All authors declare no conflicts of interest.
Data sharing statement: Raw sequencing data and associated metadata were deposited in the NCBI short-read archive with BioProject accession number PRJNA788301.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Juan Yuan, PhD, Chief Doctor, Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. hjyuan@zzu.edu.cn
Received: January 8, 2022
Peer-review started: January 8, 2022
First decision: March 9, 2022
Revised: March 19, 2022
Accepted: April 22, 2022
Article in press: April 22, 2022
Published online: June 7, 2022
Processing time: 145 Days and 8.7 Hours
Abstract
BACKGROUND

Obstructive sleep apnea (OSA)-hypopnea syndrome (OSAHS) has been recognized as a comorbidity of type 2 diabetes mellitus (T2DM); more than half of T2DM patients suffer from OSAHS. Intermittent hypoxia (IH) plays an important role in metabolic diseases, such as obesity and OSAHS, through various mechanisms, including altering the gut microecological composition and function. Therefore, it is important to study the role of gut microbiota in T2DM patients with OSAHS, which has a high incidence and is prone to several complications.

AIM

To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS.

METHODS

Seventy-eight participants were enrolled from Henan Province People’s Hospital and divided into healthy control (HC, n = 26), T2DM (n = 25), and T2DM + OSA (n = 27) groups based on their conditions. The fecal bacterial DNA of the research participants was extracted and subjected to 16S ribosomal RNA sequencing. The clinical indices, such as insulin resistance index, homocysteine (HCY) concentration, and the concentrations of inflammatory factors in the peripheral blood, were assessed and recorded.

RESULTS

Group T2DM + OSA had the highest apnea-hypopnea index (AHI) (2.3 vs 3.7 vs 13.7), oxygen desaturation index (0.65 vs 2.2 vs 9.1), HCY concentration (9.6 μmol/L vs 10.3 μmol/L vs 13.81 μmol/L) and C-reactive protein (CRP) concentrations (0.3 mg/L vs 1.43 mg/L vs 2.11 mg/L), and lowest mean oxygen saturation (97.05% vs 96.6% vs 94.7%) among the three groups. Twelve and fifteen key differences in amplicon sequence variants were identified when comparing group T2DM + OSA with groups T2DM and HC, respectively. We found progressively decreased levels of Faecalibacterium, Eubacterium, and Lachnospiraceae, and an increase in the level of Actinomyces, which strongly correlated with the HCY, CRP, fasting plasma glucose, and hemoglobin A1c concentrations, AHI, mean oxygen saturation, and insulin resistance index in group T2DM + OSA (P < 0.05).

CONCLUSION

For T2DM patients with OSAHS, IH may be involved in selective alterations of the gut microbiota, which may affect the pathophysiological development of T2DM and DM-related complications.

Keywords: Gut microbiota; Obstructive sleep apnea-hypopnea syndrome; Type 2 diabetes mellitus; Intermittent hypoxia; Obstructive sleep apnea

Core Tip: Clinically, type 2 diabetes mellitus (T2DM) patients have a significantly higher prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) than non-T2DM patients and are more prone to diabetes-related complications and metabolic syndrome, including obesity and hypertension. In recent years, the imbalance of gut microbiota has been found to be associated with various metabolic disorders. This study revealed that intermittent hypoxia was associated with changes in the gut microbiota in patients with T2DM complicated by OSAHS. These changes may be involved in the progression of metabolic disorders through increased proinflammatory factors and impaired intestinal barrier function.