Clinical significance of the genetically variable landscape of the gut microbiome in patients with gestational diabetes mellitus patients
Kunna Zhang,
Menglu Hu,
Wentao Yang,
Zhexia Hu,
Yun Rong,
Biyun Luo,
Mengjia Wang,
Yajuan Cheng,
Rui Zhang,
Ning Lv,
Qian Zhou,
Xueling Zhang
Affiliations
Kunna Zhang
Department of Obstetrics, the First Hospital of Yongnian District, Handan, Hebei Province, China
Menglu Hu
School of Medicine, Southeast University, Nanjing Province, China
Wentao Yang
School of Medicine, Southeast University, Nanjing Province, China
Zhexia Hu
Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China
Yun Rong
Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China
Biyun Luo
Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China
Mengjia Wang
Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China
Yajuan Cheng
Department of Obstetrics, the First Hospital of Yongnian District, Handan, Hebei Province, China
Rui Zhang
Department of Obstetrics, the First Hospital of Yongnian District, Handan, Hebei Province, China
Ning Lv
Department of Obstetrics & Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China; Corresponding author. Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College, No. 1 Shuaifuyuan Dongcheng District Beijing, 10073, China.
Qian Zhou
Department of Obstetrics & Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China; Corresponding author. Department of Obstetrics & Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College National Clinical Research Center for Obstetric & Gynecologic Diseases No. 1 Shuaifuyuan Dongcheng District Beijing, 100730, China.
Xueling Zhang
Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China; Corresponding author. Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, 050000, address: No. 12, Health Road, Chang 'an District, Shijiazhuang, China.
Background: The composition of the gut microbiome has been recorted to be strongly associated with gestational diabetes mellitus (GDM), but mutational characterization of the microbiome in patients with GDM has been overlooked. Here, we revealed the genetic variation landscape of the gut microbiome and assessed its clinical significance in a cohort of patients with GDM. Methods: We employed a macrogenomic dataset made up of a discovery cohort of 54 cases and a validation cohort of 220 cases to screen for high-abundance microbial flora and identified single nucleotide variants (SNVs) and insertions/deletions (indels). Subsequently, we analyzed the mutation spectra of genomes of the intestinal flora by using the previously identified SNVs and identified mutation signatures. Additionally, we utilized the Random Forest algorithm to identify key differential SNVs and elucidated their biological functions and associations with the clinicopathological parameters of GDM. Results: We screened 15 key microbial flora and found that the GDM group had more SNVs and indels in the intestinal flora than the control group, with a significant increase in C > T and T > C base mutations and were more susceptible to sequence mutations. Compared to the control group, the GDM group underwent a more significant evolution, as evidenced by the presence of a unique mutational spectrum and mutational characteristics. Random Forest algorithm analysis showed that the combined characterization of five gut microbial species and 21 SNV-related markers was effective in distinguishing between GDM and control subjects in both discovery (area under the curve (AUC) = 0.86) and validation (AUC = 0.73) sets. These markers also revealed that GDM is strongly associated with sphingolipids, galactose, and proteins containing the DUF structural domain. Conclusions: The GDM intestinal flora has unique mutational features that correlate significantly with clinicopathological involvement and may be involved in the development of the disease.
