Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing 100853, China.
Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
World J Gastroenterol. 2024 Jun 7;30(21):2777-2792. doi: 10.3748/wjg.v30.i21.2777.
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.
To reveal the transcriptomic changes in the jejunum involved in ODS.
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.
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 (, , , , , , , and ) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients ( < 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 ( < 0.01), but were higher in the SOD group than in the SO group ( < 0.001).
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.
肥胖与慢性腹泻的风险显著增加相关，这被提出为 Linghu 的肥胖-腹泻综合征（ODS）；然而，其分子机制在很大程度上尚不清楚。
揭示 ODS 相关的空肠转录组变化。
在 6 例 ODS 患者（JOD 组）、6 例肥胖无腹泻患者（JO 组）和 6 例健康对照者（JC 组）的队列中，进行高通量测序和生物信息学分析，以鉴定空肠黏膜 mRNA 表达改变和功能失调的生物学过程。在另一项包含 16 例 ODS 患者（SOD 组）、16 例肥胖无腹泻患者（SO 组）和 16 例健康对照者（SC 组）的队列中，检测血清二胺氧化酶（DAO）和 D-乳酸（D-LA）浓度，以评估肠屏障功能的变化。
JO 和 JC 组空肠黏膜的基因表达谱相似，仅有 1 个差异表达基因（DEG）。JOD 组的基因表达谱显著改变，与 JO 组相比有 411 个 DEG，与 JC 组相比有 211 个 DEG，其中 129 个重叠。这些 DEG 的富集分析表明，JOD 组的消化、吸收和营养（特别是脂质）转运等生物学过程趋于上调，而 JOD 组的 rRNA 加工、线粒体翻译、抗菌体液反应、DNA 复制和 DNA 修复等生物学过程趋于下调。8 个 DEG（、、、、、、和）可能在 ODS 的病理过程中发挥关键调节作用，其在 ODS 患者中的表达水平显著降低（<0.001）。在第二队列中，与健康对照者相比，所有肥胖个体的血清肠屏障功能标志物（DAO 和 D-LA）水平均显著升高（<0.01），但 SOD 组高于 SO 组（<0.001）。
与健康对照者和肥胖无腹泻者相比，Linghu 的 ODS 患者空肠黏膜有广泛的转录组变化，可能影响肠屏障功能，从而导致肥胖和慢性腹泻表型。
