Abstract：
BACKGROUND: Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH.
METHODS: In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2.
RESULTS: Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism.
CONCLUSIONS: Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy.
BACKGROUND: This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
METHODS: In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2.
RESULTS: Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism.
CONCLUSIONS: Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy.
BACKGROUND: This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
摘要：
背景：抗甲状腺过氧化物酶抗体（TPOAb）阳性有助于抑制甲状腺素合成。肠道微生物群可以与代谢或免疫疾病相互作用。然而,在TPOAb阳性/阴性亚临床甲状腺功能减退症(TPOAb+/TPOAb-SCH)的女性患者中,从妊娠中期(T2)到妊娠中期(T3)的肠道菌群动态尚未见报道.因此,我们旨在评估肠道菌群是否可以成为管理TPOAb+SCH的潜在治疗靶点.
方法：在这项单中心前瞻性队列研究中，我们通过对T2(20-23+6周)和T3(28-33+6周)收集的粪便样本中的16SrRNA进行测序,观察了肠道微生物群动态.TPOAb+/TPOAb-SCH根据他们在怀孕期间是否使用左甲状腺素(LT4)(LT4+/LT4-)进行分层。使用QIIME2进行微生物组生物信息学分析。线性判别分析效应大小(LEfSe)用于生物标志物的定量分析。用PICRUSt2进行功能分析。
结果：在TPOAb-（n=68）和TPOAb+（n=64）SCH组中观察到从T2到T3的不同肠道微生物群动态。TPOAb+LT4-组的特征在于富集的细菌扩增子序列变体(ASV)的Prevotella在T2和细菌,湖水螺旋藻,落叶松科,Blautia,和T3中的Agathobacter和耗尽的γ变形杆菌的ASV，肠杆菌,T2和放线菌的肠杆菌科，科氏杆菌,放线菌,Coriobacteriales,双歧杆菌,双歧杆菌科，双歧杆菌,多雷亚形族，T3中长双歧杆菌。TPOAb+LT4+组的特征是布劳特氏菌的富集细菌ASV，唾液链球菌，和T3中长双歧杆菌和耗尽的拟杆菌ASV，细菌,拟杆菌,T2中的Prevotella和T3中的Agathobacter。此外，我们确定了53种主要涉及糖的代谢功能，脂质，和氨基酸代谢。
结论：我们的结果表明，从T2到T3，肠道菌群组成的低动力学和其代谢功能的高动力学与TPOAbSCH有关。我们得出结论，肠道菌群可能是治疗妊娠期TPOAbSCH的新靶点。
背景：本研究于2021年6月10日在中国临床试验注册中心（注册号ChiCTR2100047175）进行了回顾性注册。
方法：在这项单中心前瞻性队列研究中，我们通过对T2(20-23+6周)和T3(28-33+6周)收集的粪便样本中的16SrRNA进行测序,观察了肠道微生物群动态.TPOAb+/TPOAb-SCH根据他们在怀孕期间是否使用左甲状腺素(LT4)(LT4+/LT4-)进行分层。使用QIIME2进行微生物组生物信息学分析。线性判别分析效应大小(LEfSe)用于生物标志物的定量分析。用PICRUSt2进行功能分析。
结果：在TPOAb-（n=68）和TPOAb+（n=64）SCH组中观察到从T2到T3的不同肠道微生物群动态。TPOAb+LT4-组的特征在于富集的细菌扩增子序列变体(ASV)的Prevotella在T2和细菌,湖水螺旋藻,落叶松科,Blautia,和T3中的Agathobacter和耗尽的γ变形杆菌的ASV，肠杆菌,T2和放线菌的肠杆菌科，科氏杆菌,放线菌,Coriobacteriales,双歧杆菌,双歧杆菌科，双歧杆菌,多雷亚形族，T3中长双歧杆菌。TPOAb+LT4+组的特征是布劳特氏菌的富集细菌ASV，唾液链球菌，和T3中长双歧杆菌和耗尽的拟杆菌ASV，细菌,拟杆菌,T2中的Prevotella和T3中的Agathobacter。此外，我们确定了53种主要涉及糖的代谢功能，脂质，和氨基酸代谢。
结论：我们的结果表明，从T2到T3，肠道菌群组成的低动力学和其代谢功能的高动力学与TPOAbSCH有关。我们得出结论，肠道菌群可能是治疗妊娠期TPOAbSCH的新靶点。
背景：本研究于2021年6月10日在中国临床试验注册中心（注册号ChiCTR2100047175）进行了回顾性注册。
