Evaluation of probiotics in the treatment of hypothyroidism in early pregnancy combined with small intestinal bacterial overgrowth.

The aim of this study was to investigate the association between hypothyroidism in early pregnancy and small intestinal bacterial overgrowth (SIBO) and the effect of probiotics. Patients with hypothyroidism in early pregnancy and normal pregnant women during the same period were included in the methane-hydrogen breath test to compare the incidence of SIBO, smoothed curve fit, and differences in clinical symptoms. For those who combined with SIBO, the rate of clinical symptom conversion, thyroid hormones, and changes in associated inflammatory indexes were compared after 21 days of treatment with probiotics on top of conventional levothyroxine sodium tablets. The results are as follows: (1) The incidence of combined SIBO in patients with hypothyroidism in pregnancy was 56.0%, significantly higher than the 28.0% of normal pregnant women during the same period. (2) The highest value of hydrogen plus methane gas in 90 min in pregnancy hypothyroid patients showed a significant negative correlation with FT4 (p < .001, SD = 0.169). (3) Abdominal distension symptoms were significantly increased in both groups after combined SIBO (p = .036, p = .025), and the conversion rate after treatment was 69.2% and 75.0%, respectively. (4) In hypothyroidism, pregnancy combined with SIBO, TSH, and CRP was higher before treatment (p = .001, p = .012) and decreased significantly after treatment (p = .001, p = .008). Hypothyroidism in early pregnancy is associated with SIBO, and probiotic treatment is significantly effective.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Probiotics and Prebiotics in Subclinical Hypothyroidism of Pregnancy with Small Intestinal Bacterial Overgrowth.

Evaluating efficacy of probiotics combined with prebiotics in small intestinal bacterial overgrowth (SIBO) in subclinical hypothyroidism (SCH) in the second trimester. We collected data from 78 pregnant women with SCH (SCH group) and 74 normal pregnant women (control group) in second trimester, compare the differences in high sensitivity C-reactive protein (hsCRP), result of lactulose methane-hydrogen breath test and gastrointestinal symptoms assessed by GSRS scale between two groups. In SCH group, 32 patients with SIBO were selected as intervention group. Treatment with probiotics + prebiotics for 21 days; The differences of lipid metabolism, hsCRP, thyroid function level, methane-hydrogen breath test results and GSRS scores before and after treatment were compared to evaluate the therapeutic effect. (1) The positive rate of SIBO and methane, hsCRP levels in SCH group were higher than those in control group (P < 0.05), the total score of GSRS scale, mean score of indigestion syndrome, and constipation syndrome in SCH group were higher (P < 0.05). (2) The mean abundance of hydrogen and methane were higher in SCH group. (3) After treatment, serum levels of thyrotropin(TSH), total cholesterol(TC), triglyceride(TG), low-density lipoprotein (LDL), and hsCRP in intervention group were decreased, and high-density lipoprotein (HDL) was increased compared with before treatment (P < 0.05). (4) After treatment, methane positive rate, total score of GSRS scale, mean score of diarrhea syndrome, dyspepsia syndrome, and constipation syndrome were decreased (P < 0.05). (5) The average abundance of methane and hydrogen were lower. Probiotics combined with prebiotics are effective in the treatment of SIBO in pregnant SCH patients.Clinical Trial Registration Number: ChiCTR1900026326.

Correlation between the intestinal microflora and peripheral blood Th1/Th2 balance in hypothyroidism during the first half of pregnancy.

Objective: This study aimed to investigate the relationship between intestinal microflora characteristics and the peripheral blood T helper cell (Th)1/Th2 balance in patients with hypothyroidism during the first half of pregnancy. Methods: The Th1/Th2 ratios in the peripheral blood of pregnant women in the hypothyroidism and control groups were determined using flow cytometry. The cytometric bead array assay was used to determine the serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Moreover, 16S rRNA amplicon sequencing was used to determine the intestinal microbial composition in the two groups. Finally, the relationships between intestinal microflora, Th1/Th2 cells, cytokines, and clinical indicators were analyzed. Results: C-reactive protein levels were higher in the hypothyroidism group than in the control group. In contrast to the control group, the hypothyroidism group showed an increase in Th1 cells and the Th1/Th2 ratio, and a decrease in Th2 cells. The hypothyroidism group had higher serum IL-2, TNF-α, and IFN-γ levels, and lower IL-10 levels, than the control group. The richness of the intestinal microflora in the hypothyroidism group increased whereas the diversity decreased. The linear discriminant analysis effect size revealed that the hypothyroidism group had a higher abundance of Prevotella and Faecalibacterium, but a lower abundance of Bacteroides, compared to the control group. Prevotella was positively correlated with Th1 cells, the Th1/2 ratio, and TNF-α. Bacteroides was positively correlated with Th2 cells and IL-10, but negatively correlated with Th1 cells, the Th1/2 ratio, TNF-α, and IFN-γ. The thyroid peroxidase antibody level was directly proportional to TNF-α. Conclusion: A Th1/Th2 imbalance occurs in patients with hypothyroidism during the first half of pregnancy. Disorders of the intestinal microflora may lead to hypothyroidism during pregnancy by affecting the Th1/Th2 balance.

Efficacy evaluation of probiotics combined with prebiotics in patients with clinical hypothyroidism complicated with small intestinal bacterial overgrowth during the second trimester of pregnancy.

Objective: To explore the effect of probiotics combined with prebiotics on clinical hypothyroidism during pregnancy combined with small intestinal bacterial overgrowth. Methods: (1) In total, 441 pregnant women were included in this study. A total of 231 patients with clinical hypothyroidism during the second trimester of pregnancy and 210 normal pregnant women were enrolled in the lactulose methane-hydrogen breath test. The positive rate of intestinal bacterial overgrowth (SIBO), gastrointestinal symptoms, thyroid function and inflammatory factors were compared between the two groups by chi-square test and two independent sample t-test. (2) SIBO-positive patients in the clinical hypothyroidism group during pregnancy (n=112) were treated with probiotics combined with prebiotics based on conventional levothyroxine sodium tablets treatment. The changes in the methane-hydrogen breath test, gastrointestinal symptoms, thyroid function and inflammatory factors were compared before treatment (G0) and 21 days after treatment (G21) by chi-square test and paired sample t test. Results: (1) The positive rates of SIBO in pregnant women in the clinical hypothyroidism group and control group were 48.5% and 24.8%, respectively. (2) The incidence of abdominal distention and constipation in the clinical hypothyroidism group was significantly higher than that in the control group, and the risk of abdominal distention and constipation in SIBO-positive pregnant women was higher than that in SIBO-negative pregnant women. (3) The serum levels of hypersensitive C-reactive protein (hsCRP), IL-10, IL-6, TNF-α, low-density lipoprotein (LDL), total cholesterol (TC), free fatty acids (FFAs) and apolipoprotein B (ApoB) in the hypothyroidism group during pregnancy were higher than those in the control group. (4) After 21 days of probiotics combined with prebiotics, the incidence of pure methane positivity in the methane-hydrogen breath test in the G21 group was significantly reduced, and the average abundance of hydrogen and methane at each time point in the G21 group was lower than that in the G0 group. (5) The incidence of constipation in the G21 group was significantly lower than before treatment. (6) The levels of serum TSH, hsCRP, IL-6, TNF-α, TC and LDL in pregnant women after probiotics combined with prebiotics were lower than those before treatment. Conclusion: Probiotics combined with prebiotics are effective in the treatment of pregnant patients with clinical hypothyroidism complicated with SIBO, providing a new idea to treat pregnant patients with clinical hypothyroidism complicated with SIBO.

Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes.

Subclinical hypothyroidism (SCH) has become a prevalent complication in pregnancy. Recent research links SCH to disturbed thyroid lipid profile; however, it is unclear how lipid metabolism disorders contribute to the pathogenesis of SCH during pregnancy. Thus, we used nontargeted lipidomics to identify and compare the lipids and metabolites expressed by pregnant women with SCH and healthy pregnant women. Multivariate analysis revealed 143 lipid molecules differentially expressed between the SCH group and the control group. Based on fold change, 30 differentially expressed lipid metabolites are potential biomarkers. KEGG pathway enrichment analysis showed that the differentially expressed metabolites participate in several pathways, including response to pathogenic Escherichia coli infection, regulation of lipolysis in adipocytes, metabolic pathways, glycerophospholipid metabolism, and fat digestion and absorption pathways. Correlation analyses revealed sphingomyelin (SM) and phosphatidylcholine (PC) positively correlate to tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), while phosphatidylglycerol (PG), and phosphatidylinositol (PI) negatively correlate with them. In addition, PG positively correlates to birth weight. Thus, the lipid profile of pregnant women with SCH is significantly different from that of healthy pregnant women. Lipid molecules associated with the differential lipid metabolism, such as SM, phosphatidylethanolamine (PE), and PI, should be further investigated for their roles in the pathogenesis of SCH in pregnancy, as they might be targets for reducing the incidence of adverse pregnancy outcomes.

Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women.

Objective: To evaluate the small intestinal bacterial overgrowth (SIBO) of subclinical hypothyroidism of pregnant women, and explore their possible relevance. Methods: In total, 224 pregnant women with subclinical hypothyroidism during pregnancy (study group) and 196 pregnant women whose thyroid function was normal (control group) were enrolled in this study. Lactulose-based hydrogen and methane breath test was performed to evaluate the growth of intestinal bacteria. The serum-free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), body mass index (BMI) and gastrointestinal symptoms were detected and recorded. Results: The positive rates of SIBO were 56.7% and 31.6% in study group and control group, respectively. The levels of C response protein (CRP), abdominal distension and constipation in study group were higher than those in the control group. The risk of abdominal distension and constipation in SIBO-positive pregnant women were higher than that in SIBO-negative pregnant women, and the BMI of SIBO-positive patients in the two groups was lower than that of SIBO-negative patients in each group. In addition, the TPOAb-positive rate and TSH levels were higher but the FT4 level was lower in SIBO-positive patients compared to SIBO-negative patients in study group. Conclusion: The occurrence of subclinical hypothyroidism is related to SIBO, and the excessive growth of small intestinal bacteria may affect gastrointestinal symptoms. Clinical Trial: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026326.

Application of methane and hydrogen-based breath test in the study of gestational diabetes mellitus and intestinal microbes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. The purpose of this study was to compare the incidence of small intestinal bacterial overgrowth (SIBO) in patients with GDM and the control group by methane and hydrogen lactulose breath test (LBT), and to explore its relationship with inflammation, vitamins, and the outcomes of maternal and child. METHODS: LBT was detected in 220 GDM patients, 160 pregnancy control patients and 160 pre-pregnancy control patients. The fasting blood glucose, white blood cells, vitamin A, D, E, neonatal weight, neonatal blood glucose and so on were compared and analyzed. RESULTS: There was no statistical significance in the general data of the three groups. The proportion of abdominal distension in the GDM group was higher than that in the other two groups (P < 0.001). The positive rates of SIBO + in GDM group, gestational control group and pre-pregnancy control group were 54.55%, 27.50% and 14.38%, respectively. The average abundance of hydrogen and methane in GDM group was significantly higher than that in control group at each time point. In the GDM group, SIBO + subjects had higher levels of fasting blood glucose, glycoglycated hemoglobin, C-reactive protein, neonatal weight, and lower levels of vitamin D and neonatal blood glucose (P < 0.001). CONCLUSION: Patients with GDM have a high incidence of SIBO, and SIBO may further increase their blood glucose by affecting inflammatory response and vitamin level, and even affect the outcome of mother and child.

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy.

Objective: To investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy. Methods: The plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis. Results: (1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p<0.05). (3) KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways. (4) Serum cholesterol (TC) and triglyceride (TG) levels and hypertensive disorder complicating pregnancy (HDCP) were higher in the SCH group (p<0.05), and newborn birth weight (BW) was lower than that in the control group (p<0.05). (5) SIBO was negatively correlated with glycocholic acid and BW, and positively correlated with TC. Glycocholic acid was negatively correlated with TG but positively correlated with BW. TG was positively correlated with HDCP. Conclusion: Differential metabolites in the SCH group during pregnancy were disordered with small intestinal bacteria, which may affect pregnancy outcomes, and bile acids and cholesterol may be potential biomarkers for studying their mechanism of action.

Plasma Lipid Profile and Intestinal Microflora in Pregnancy Women With Hypothyroidism and Their Correlation With Pregnancy Outcomes.

Objective: To investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes. Methods: In total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed. Results: Patients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05). Conclusion: The lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.

Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes.

The purpose of this study was to explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy. In this study, oral and intestinal microbial composition was surveyed by using the 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features by using the quantitative real-time PCR (qPCR) approach in 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes. The 16S rRNA results showed that the relative abundances of Gammaproteobacteria were higher in pregnant women in the hypothyroidism group than in those in the control group, whereas the levels of Firmicutes were higher in the control group than in the hypothyroidism group. The serum C-reactive protein level, the weight gain during pregnancy, and the incidence of fetal distress were higher in the hypothyroidism group than in the control group. The QPCR results also showed the same changes of the intestinal microbiota in the two groups. There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.

Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation.

Maternal microbiota is involved in many metabolic diseases. However, its role in the pathophysiology of gestational diabetes mellitus (GDM) remains unclear. In this case-control study, we performed a 16S rRNA sequencing-based microbial survey to compare the intestinal and oral microflora at third trimester during pregnancy between 30 GDM and 31 normal controls. Sequentially, a correlation-based network analysis was further performed to explore the interactions among microbiota, maternal and infant blood sugar, and inflammatory markers. Our results show that, compared with controls, the GDM cases showed significant differences in ß-diversity and increased Gammaproteobacteria and Hemophilus in intestinal microbiota. Furthermore, the GDM cases showed lower α-diversity, increased Selenomonas and Bifidobacterium, and decreased Fusobacteria and Leptotrichia in oral microbiota. The ROC curve showed the area under the curve to be equal to 0.70 and 0.66 when using oral Leptotrichia or gut Hemophilus, respectively, to predict GDM status. In addition, the components and topography of microbial cooccurrence and coexclusion network were quite distinct by GDM status. In summary, intestinal and oral microorganisms in pregnant women are closely related to the status of GDM in the third trimester of pregnancy. The changes of intestinal and oral microbial features may be noninvasive biomarkers for monitoring the health management of GDM pregnancy.

Relationship between unexplained recurrent pregnancy loss and 5,10-methylenetetrahydrofolate reductase) polymorphisms.

OBJECTIVE: To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of folate metabolism-related genes. DESIGN: A case-control study. SETTING: Urban university-based hospital. PATIENT(S): Two-hundred and eighteen women with URPL and 264 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fluorescence quantitative polymerase chain reaction examination of sequences of the C677T and A1298C loci of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. RESULT(S): The frequency of the T allele at the MTHFR C677T locus in the URPL group was statistically significantly higher compared with the control group (odds ratio [OR] 1.324; 95% confidence interval [CI], 1.014-1.729), and the presence of the CC+CT genotype was statistically significantly reduced in the URPL group (OR 0.678; 95% CI, 0.471-0.974). The frequency of the C allele at the MTHFR A1298C locus in the URPL group was statistically significantly higher than that in the control group (OR 1.557; 95% CI, 1.066-2.275), and the presence of the CC+AC genotype was statistically significantly elevated in the URPL group (OR 1.740; 95% CI, 1.137-2.661). The frequency of MTHFR 677CT/1298AC compound genotypes in the URPL group was 6.589-fold higher compared with the control group. Most patients in the URPL group carried two mutant genes (69.3%), and the percentage of patients with two mutant genes was statistically significantly higher than in the control group (OR 4.996; 95% CI, 1.650-15.129). CONCLUSION(S): The MTHFR 1298AC genotype and composite heterozygote genotype (677CT/1298AC) are risk factors for URPL. The risk of URPL is highest in women carrying two mutations of A1298C and C677T locus in MTHFR.