Association of Gut Microbiota with Hypertensive Disorders in Patients with Gestational Diabetes Mellitus

Abstract

Background Pregnant women with gestational diabetes mellitus (GDM) are often comorbid with hypertensive disorders of pregnancy (HDP), which can severely impact pregnancy health and delivery outcomes. The relationship between gut microbiota and pregnancy health has received increasing attention, but its association with concurrent HDP in GDM remains to be investigated. Objective To explore the association between gut microbiota characteristics and concurrent HDP in GDM patients. Methods The 204 patients with GDM who underwent prenatal examination at the Hangzhou Women's Hospital from August 2019 to January 2020 were selected as the study subjects. Pregnant women diagnosed with GDM only were categorized as the GDM group (n=181), while those concurrently diagnosed with GDM and HDP were categorized as the GDM with concurrent HDP group (n=23). Clinical data and inflammation detection markers of the enrolled pregnant women were collected, and fecal samples of the same period were retained for gut microbiota 16S rDNA amplicon sequencing analysis. LEfSe analysis was used to compare microbiota composition between the two groups at the phylum, family and genus levels, and to identify distinct bacterial enrichments. Logistic regression analysis was performed to identify gut microbiota characteristics associated with concurrent HDP in GDM. Spearman's rank correlation analysis was performed to explore the association between gut microbiota and inflammatory markers. Results No significant differences were found in overall gut microbiota composition and relative abundances of major phyla between the two groups (P>0.05). LEfSe analysis on family level showed that the Veillonellaceae family was enriched in the GDM with concurrent HDP group (P<0.05), while Mollicutes RF39 unclassified family and Lachnospiraceae were depleted (P<0.05). At the genus level, Dialister, Intestinibacter, Eubacterium and Parasutterella were enriched in the GDM with concurrent HDP group (P<0.05), whereas [Eubacterium] xylanophilum group, Ruminiclostridium 6, Mollicutes RF39 unclassified genus and Lachnospiraceae unclassified genus were enriched in the GDM group (P<0.05). Logistic regression analysis results showed increased abundances of Veillonellaceae (OR=1.06, 95%CI=1.01-1.11), Dialister (OR=1.26, 95%CI=1.10-1.45) and Intestinibacter (OR=2.07, 95%CI=1.12-3.84) were independent risk factors for concurrent HDP in GDM (P<0.05), while increased Lachnospiraceae was a protective factor (P<0.05). Spearman's rank correlation analysis results showed Veillonellaceae was positively correlated with the proportion of monocytes (rs=0.149, P<0.05) ; Dialister was positively correlated with leukocyte count, eosinophil leukocyte, and eosinophil count (rs=0.151, 0.163, 0.171, P<0.05) . Conclusion Increased abundances of Veillonellaceae, Dialister and Intestinibacter are independent risk factors for concurrent HDP in GDM pregnant women, while increased abundance of Lachnospiraceae unclassified genus is a protective factor. Veillonellaceae and Dialister are positively correlated with multiple inflammatory markers. Gut microbiota may be an important risk factor for concurrent HDP in GDM.

Keywords

• diabetes, gestational|hypertension, pregnancy-induced|intestinal flora|lefse analysis|inflammation|root cause analysis