Biological Characteristics Of The Gut And Oral Microbiota In Hypothyroidism Patients With Abnormal Thyroperoxidase Antibodies In The Third Trimester Of Pregnancy And Correlations With Maternal And Infant Outcomes

BackgroundThe incidence of hypothyroidism,which can cause a variety of maternal and fetal complications and serious harm to the health of the mother and child during pregnancy,is increasing^[1].The most important causes of hypothyroidism during pregnancy is autoimmune thyroid disease（AITD）^[2].Thyroid peroxidase antibodies（TPOAbs）are the most sensitive and accurate indicators for the diagnosis of AITD,serve as biomarkers for diagnosing AITD,and are closely related to thyroid function^[3].Increased TPOAbs indicate adverse progression of the disease^[4].Studies of Kiseleva EP et al.^[5]have shown the correlation between TPOAbs and intestinal microbiota.However,the specific mechanism of interaction between TPOAbs abnormality and intestinal microbiota during pregnancy is still not clear.Intestinal microbiota and oral microbiota which complement each other are important components of the human microbiome.Oral microbiome is an important component of the human microbiome,including hundreds to thousands of different species.Systematic data on the relationship between TPOAbs abnormalities of hypothyroidism and oral microbiota during pregnancy are rare.Biological characteristics of intestinal and oral microbiota with abnormal TPOAbs of hypothyroidism in the third trimester of pregnancy and correlation of maternal and child outcomes were analyzed.ObjectiveWe aimed to study the biological characteristics of intestinal and oral microbiota in positive TPOAbs with hypothyroidism in the third trimester of pregnancy and their correlation with maternal and infant outcomes by 16S rRNA gene sequencing technology,so as to provide a new direction to reduce the adverse effects of TPOAbs abnormalities with hypothyroidism on maternal and child outcomes.MethodIn this study,pregnant women who were examined in the outpatient clinic of the third affiliated Hospital of Zhengzhou University from September,2018 to October,2019 and plan to give birth in our hospital were selected.The gestational weeks were 37-41 weeks.According to our inclusion and exclusion criteria,the study of intestinal microbiota randomly selected 20 cases of hypothyroidism patients with positive TPOAbs in late pregnancy（HP group）and 20 cases of hypothyroidism patients with negative TPOAbs in late pregnancy（HN group）as the research subjects.we also selected randomly 20 cases of hypothyroidism patients with positive TPOAbs（HP group）and 20 cases of hypothyroidism patients with negative TPOAbs（HN group）and 27 cases of healthy pregnant women（NC group）in the same period as the normal control group in the study of oral microbiota.The pregnant women with hypothyroidism during pregnancy were diagnosed with hypothyroidism before the establishment of the perinatal insurance file,and were given levothyroxine sodium tablets for standardized treatment.DNA was extracted from the fecal and oral samples and 16S rRNA gene sequencing was done.About 8 ml fasting venous blood in the morning of all subjects was obtained to analyze the inflammatory and immune indicators.The biological characteristics of intestinal and oral microbiota in patients with abnormal TPOAbs in late pregnancy were studied,and the correlation between microbiota of patients with abnormal TPOAbs and inflammatory and immune indexes was analyzed.Results（1）In the intestinal microbiota,16S rRNA sequencing results showed that the relative abundance of Bifidobacterium in the gut microbiota of the HP group was increased,while the abundance of Lachnospira was decreased.The change was also verified by q PCR.（2）Serological indicators suggested that the HP group had higher C-reactive protein（CRP）,interleukin（IL）-2,and IL-6 levels.（3）There was a positive correlation between Bifidobacterium and TPOAbs.Lachnospira and CRP were negatively correlated,as were Lachnospira and IL-6.（4）The weight of newborns in the HP group was lower than that in the HN group,and the incidence rates of amniotic fluid contamination,neonatal asphyxia,and neonatal distress in the HP group were higher than those in the HN group.（5）In the intestinal microbiota,16S rRNA sequencing results showed that the dominant bacteria in the oral flora of HP group were Bididobacteriaceae and Lactobacilaceae.（6）There were significant differences inαdiversity and weight-Uni Frac and unweight-Uni Frac ofβdiversity in HP group and HN group and NC group.（7）In the oral microbiota,the abundance of Bididobacteriaceae in the HP group was increased,and the abundance of Bacilli was decreased.（8）In the oral microbiota,there were significant differences in white blood cells,C-reactive protein,FT4,TSH and TPOAbs levels in HP group and HN group and NC group.ConclusionsTPOAbs abnormality in patients with hypothyroidism during late pregnancy is closely correlated with gut and oral microbiota,and Bifidobacterium and Lachnospira may be noninvasive biomarkers to improve TPOAbs abnormalities in late pregnancy.