Investigating the relationship between intestinal microbiota and Th1/Th2/Th17 imbalance in subclinical hypothyroidism during the first half of pregnancy: a multi-omics approach.

BACKGROUND: Gestational subclinical hypothyroidism (SCH), marked by elevated Thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4), links to adverse perinatal outcomes. During early pregnancy (< 20 weeks), maternal thyroid hormones are crucial for fetal neurodevelopment, with deficiencies risking irreversible deficits. SCH pregnancies show gut microbiota alterations and metabolic dysregulation. Emerging evidence suggests these changes may drive Th(helper T cells)1/Th2/Th17 immune imbalance, though mechanisms remain unclear. This study combines metagenomics and lipidomics to investigate gut microbiota-Th1/Th2/Th17 interactions in patients with SCH in the first 20 weeks during pregnancy. METHODS: This study included 20 pregnant women with SCH (SCH group) in the first half of pregnancy (≤ 20 gestational weeks) and 20 normal pregnant women (CON group) in the same period. Collect fecal and blood samples from both groups. Metagenomic sequencing was used to determine the differences in the composition of the intestinal microbiota between the two groups, and non-targeted lipidomics was used to compare the lipid differences between the two groups. Flow cytometry was used to assess Th1, Th2 and Th17 cells in peripheral blood, and a cell microbead array was used to determine cytokine levels. RESULTS: (1) Metagenomic sequencing showed an increased abundance of Faecalibacterium prausnitzii and a decreased abundance of Bacteroides uniformis in the SCH group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated significant enrichment in lipid and polysaccharide biosynthesis and mucopolysaccharide biodegradation pathways in the SCH group. (2) Lipidomics identified 692 different lipids, with Triglyceride (TG) being the most significant. KEGG pathway analysis revealed that TG was mainly concentrated in the Th1, Th2, and Th17 cell differentiation pathways. (3) Additionally, serological indicators of the two groups showed that TSH, Interleukin (IL)-2,IL-10, Tumor necrosis factor (TNF)-α, TG, Th1, and Th17 in the SCH group were higher than those in the CON group, while Th2 was significantly lower (P < 0.05). CONCLUSION: In the first half of pregnancy, patients with SCH may experience intestinal microbiota disorder, characterized by increased levels of Faecalibacterium prausnitzii and decreased levels of Bacteroides uniformis, at the same time, it was accompanied by an increase in TG synthesis and a Th1/Th2/Th17 imbalance, these factors may be involved in the occurrence of SCH during pregnancy.