Hashimoto’s Thyroiditis

What Was Studied?

This study systematically investigated alterations in the gut microbiota composition in patients with Hashimoto’s thyroiditis (HT), an organ-specific autoimmune disease, compared to healthy controls. The researchers used 16S rRNA sequencing to profile and compare the gut microbiota of 50 HT patients and 27 matched healthy controls. The study aimed to identify microbial biomarkers associated with HT and their correlations with clinical parameters, such as thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab) levels.

Who Was Studied?

The study involved two cohorts: an exploration cohort of 28 HT patients and 16 healthy controls, and a validation cohort of 22 HT patients and 11 healthy controls. All participants were of Han Chinese ethnicity, aged between 18 and 65 years, and matched for age, sex, and BMI. Patients included were euthyroid and free from confounding conditions or recent medications that could affect the gut microbiota.

Key Findings

The study revealed significant differences in the gut microbiota composition between HT patients and healthy controls, though overall bacterial diversity and richness were similar. HT patients exhibited a marked increase in Firmicutes and a reduction in Bacteroidetes, with a significantly higher Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, the abundances of Blautia, Roseburia, Ruminococcus_torques_group, and Eubacterium_hallii_group were significantly increased in HT patients. In contrast, beneficial genera like Bacteroides, Fecalibacterium, and Prevotella_9 were significantly decreased.

The researchers identified 27 genera with significant differences between HT patients and controls using linear discriminant analysis effect size (LEfSe). Ten genera, including Bacteroides and Fecalibacterium, were highlighted as potential biomarkers, achieving high diagnostic accuracy with AUC values of 0.91 and 0.88 in the exploration and validation cohorts, respectively.

Microbiota changes were correlated with clinical parameters. For instance, increased levels of Blautia and Dorea were positively associated with TPO-Ab and TG-Ab, while reduced levels of Fecalibacterium and Bacteroides correlated inversely with these antibodies.

Greatest Implications

The findings highlight the potential role of gut dysbiosis in the pathogenesis of HT. The observed microbial shifts suggest a loss of anti-inflammatory and barrier-supporting taxa, such as Fecalibacterium, and an increase in pro-inflammatory or mucin-degrading taxa, such as Ruminococcus_torques_group. This dysbiosis may contribute to immune activation and thyroid autoimmunity through mechanisms like increased intestinal permeability and molecular mimicry. Additionally, the identified microbial biomarkers could serve as non-invasive tools for HT diagnosis and disease monitoring. However, longitudinal studies and experimental validation are needed to confirm causality and explore therapeutic interventions targeting the gut microbiota.

What Was Studied?

Integrative analysis reveals novel gut microbiota-transcriptome signatures for Hashimoto's thyroiditis, aiding early diagnosis and treatment.This study explored the molecular signatures of Hashimoto’s thyroiditis (HT) through an integrative analysis of gut microbiome and host transcriptome (miRNA/mRNA). It aimed to identify novel molecular markers and elucidate the gut-thyroid axis, using data from 31 early HT patients and 30 healthy controls across discovery and validation cohorts. The study sought to uncover interactions between the gut microbiota and host gene expression, providing insights into HT pathogenesis.

Who Was Studied?

Participants included 31 early HT patients and 30 healthy individuals aged 18–65. HT cases were defined by elevated thyroid antibodies (TPOAb/TGAb) and morphological abnormalities while maintaining normal thyroid function. Exclusions included antibiotic or probiotic use, significant dietary changes, or comorbid conditions. Blood and fecal samples were collected for transcriptomic and metagenomic sequencing.

What Were the Most Important Findings?

The study identified subtle but significant gut microbiota alterations in early HT patients. While alpha diversity was unchanged, beta diversity analysis revealed compositional shifts, including increased Bacillota_A and Spirochaetota at the phylum level and significant differences in 24 genera and 67 species. Beneficial microbes like Barnesiella intestinihominis were reduced, while opportunistic pathogens like Peptostreptococcus were enriched. Host transcriptome analysis identified 1975 downregulated and 1821 upregulated mRNAs, alongside 27 miRNAs. Immune and inflammation-related pathways were enriched, with hsa-miR-548aq-3p and hsa-miR-374a-5p playing key roles. Key molecular signatures included three bacterial species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, Enterocloster_citroniae) and six RNAs (e.g., GADD45A, IRS2, SMAD6). These integrated signatures demonstrated strong diagnostic potential (AUC=0.95) in distinguishing HT patients from healthy controls.

What Are the Greatest Implications?

This research advances understanding of the gut-thyroid axis and provides a robust framework for early HT diagnosis and treatment. Molecular signatures identified offer potential for targeted therapies, including microbiome modulation. For example, restoring beneficial microbes such as Barnesiella intestinihominis or targeting specific pathogenic species may offer therapeutic benefits. Integration of gut microbiota and transcriptome data sets a precedent for multidimensional biomarker development in autoimmune conditions.

What Was Studied?

This study examined alterations in the gut microbiota composition of patients with Hashimoto's thyroiditis (HT). It aimed to investigate the relationship between intestinal dysbiosis and HT through quantitative and qualitative analysis of gut microbial diversity and composition using techniques such as PCR-DGGE, real-time PCR, and pyrosequencing of 16S rRNA genes.

Who Was Studied?

The study analyzed fecal samples from 29 HT patients and 12 healthy individuals aged 40–60 years. Patients were diagnosed based on elevated thyroid antibodies (TPOAb and TGAb) and other clinical markers, including TSH and T4 levels. Healthy controls had normal thyroid function and no history of antibiotic or probiotic use in the 60 days preceding the study.

What Were the Most Important Findings?

The study revealed significant gut microbiota dysbiosis in Hashimoto’s thyroiditis (HT) patients compared to healthy controls. HT patients exhibited an increased abundance of inflammatory phyla like Proteobacteria and decreased beneficial phyla such as Firmicutes and Bacteroidetes. At the genus level, Escherichia-Shigella and Parasutterella were elevated, while anti-inflammatory genera such as Prevotella_9 and Dialister were significantly reduced. Escherichia coli was particularly overrepresented, potentially contributing to intestinal barrier disruption and inflammation linked to thyroid autoimmunity.

Real-time PCR showed significant reductions in Bifidobacterium and Lactobacillus, essential for producing immune-regulating SCFAs, while alpha diversity indicated bacterial overgrowth in HT patients. Functional diversity measures showed no significant changes, pointing to microbial imbalance rather than increased functional diversity. Pyrosequencing confirmed these findings, demonstrating a distinct microbial profile in HT patients. These results highlight the role of gut dysbiosis in HT pathogenesis and suggest potential therapeutic strategies targeting microbiome restoration.

What Are the Greatest Implications?

This study highlights gut microbiota dysbiosis as a potential contributor to the pathogenesis of HT. The findings suggest that the overrepresentation of inflammatory and opportunistic pathogens, such as Escherichia coli and Escherichia-Shigella, coupled with the reduction of beneficial microbes like Bifidobacterium and Lactobacillus, may influence immune regulation and thyroid autoimmunity. Restoring microbial balance through probiotics, dietary interventions, or targeted microbiome therapies could serve as novel strategies for managing HT. These results underscore the critical role of gut health in autoimmune diseases and provide a foundation for developing microbiome-targeted interventions.

What was studied?

This study investigated the taxonomic and functional gut microbiota profiles of euthyroid individuals with and without thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid diseases such as Hashimoto’s thyroiditis. The goal was to assess whether gut microbiota composition differs in individuals with TPOAb before the clinical onset of autoimmune thyroid disease and to evaluate ethnic variations in thyroid biomarkers.

Who was studied?

The study examined 1,468 euthyroid participants aged 35 years and older from the multiethnic HELIUS cohort, including European Dutch, Moroccan, and Turkish individuals. Of these, 159 participants were TPOAb-positive, and 1,309 were TPOAb-negative. Fecal microbiota composition was analyzed using 16S rRNA sequencing.

What were the most important findings?

The study revealed no significant differences in global gut microbiota diversity (alpha or beta diversity) between TPOAb-positive and TPOAb-negative individuals.However, 138 microbial taxa were nominally associated with TPOAb presence, with 13 taxa consistently significant across multiple statistical methods. Among the most notable taxa, members of the Desulfovibrionaceae family were positively associated with TPOAb presence, while certain taxa from the Clostridiales vadin BB60 group were negatively associated. Functional pathway analysis indicated reduced abundance of pathways related to D-glucarate degradation, glycolysis, and adenosylcobalamin biosynthesis in TPOAb-positive participants, although none of these associations were statistically significant after correction for multiple testing. Ethnicity emerged as a more significant factor in microbiota variation than TPOAb status, with no ethnic differences in thyroid biomarker levels found.

What are the greatest implications of this study?

This study underscores the role of gut microbiota in the early stages of autoimmune thyroid disease, suggesting that microbial alterations may not be the primary driver of TPOAb seroconversion. However, the associations between specific taxa and TPOAb presence warrant further investigation to elucidate their potential involvement in disease progression. The lack of robust differences in microbiota composition between groups highlights the need for longitudinal studies to determine causal relationships between gut dysbiosis and autoimmune thyroiditis. Moreover, the findings emphasize the importance of considering ethnic diversity in microbiome research to ensure accurate interpretation of results.