Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2024; 30(21): 2777-2792
Published online Jun 7, 2024. doi: 10.3748/wjg.v30.i21.2777
Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome: A pilot study
Xiao-Tong Niu, Xiang-Yao Wang, Yan Wang, Ke Han, Nan Ru, Jing-Yuan Xiang, En-Qiang Linghu
Xiao-Tong Niu, Ke Han, Jing-Yuan Xiang, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing 100853, China
Xiao-Tong Niu, Xiang-Yao Wang, Yan Wang, Ke Han, Nan Ru, Jing-Yuan Xiang, En-Qiang Linghu, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Yan Wang, School of Medicine, Nankai University, Tianjin 300071, China
Co-first authors: Xiao-Tong Niu and Xiang-Yao Wang.
Author contributions: Linghu EQ designed the research; Niu XT, Wang XY, Ru N and Xiang JY conducted the research; Niu XT, Wang Y and Han K analyzed the data; Niu XT and Wang XY wrote the manuscript; All authors have read and approve the final manuscript. Niu XT and Wang XY contributed equally to this work as co-first authors. The reasons for designating Niu XT and Wang XY as co-first authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-first authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-first authors best reflect this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Niu XT and Wang XY contributed efforts of equal substance throughout the research process. The choice of these researchers as co-first authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. In summary, we believe that designating Niu XT and Wang XY as co-first authors is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Institutional review board statement: This study was approved by the ethics committee of Chinese PLA General Hospital (No. S2022-677-01).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Dr. Linghu has nothing to disclose.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
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: En-Qiang Linghu, MD, PhD, Chief Physician, Director, Professor, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. linghuenqiang@vip.sina.com
Received: April 18, 2024
Revised: May 17, 2024
Accepted: May 20, 2024
Published online: June 7, 2024
Processing time: 45 Days and 21.9 Hours
Abstract
BACKGROUND

Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu’s obesity-diarrhea syndrome (ODS); however, its molecular mechanisms are largely unknown.

AIM

To reveal the transcriptomic changes in the jejunum involved in ODS.

METHODS

In a cohort of 6 ODS patients (JOD group), 6 obese people without diarrhea (JO group), and 6 healthy controls (JC group), high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes. In another cohort of 16 ODS patients (SOD group), 16 obese people without diarrhea (SO group), and 16 healthy controls (SC group), serum diamine oxidase (DAO) and D-lactate (D-LA) concentrations were detected to assess changes in intestinal barrier function.

RESULTS

The gene expression profiles of jejunal mucosa in the JO and JC groups were similar, with only 1 differentially expressed gene (DEG). The gene expression profile of the JOD group was significantly changed, with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group, 129 of which overlapped. The enrichment analysis of these DEGs showed that the biological processes such as digestion, absorption, and transport of nutrients (especially lipids) tended to be up-regulated in the JOD group, while the biological processes such as rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair tended to be down-regulated in the JOD group. Eight DEGs (CDT1, NHP2, EXOSC5, EPN3, NME1, REG3A, PLA2G2A, and PRSS2) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients (P < 0.001). In the second cohort, compared with healthy controls, the levels of serum intestinal barrier function markers (DAO and D-LA) were significantly increased in all obese individuals (P < 0.01), but were higher in the SOD group than in the SO group (P < 0.001).

CONCLUSION

Compared with healthy controls and obese individuals without diarrhea, patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa, likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.

Keywords: Obesity; Chronic diarrhea; Jejunum; Transcriptome; Intestinal barrier

Core Tip: This study analyzed the transcriptomic characteristics of the jejunal mucosa in patients with Linghu’s obesity-diarrhea syndrome (ODS). The jejunal gene expression profile of obese people without diarrhea was similar to that of healthy controls. However, the jejunal gene expression profile of ODS patients showed significant changes, characterized by the up-regulation of nutrient absorption, digestion, and transport and the down-regulation of rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair. In addition, although intestinal barrier damage was present in all obese individuals, it appeared to be more severe in ODS patients.