Mendelian Randomization Reveals Causal Gut Microbiota Signatures in Six Thyroid Diseases Original paper
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
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Graves Disease
Graves Disease
OverviewGraves’ Disease (GD) affects approximately 0.5% of the population, predominantly women. First-line treatment options—antithyroid medications, radioactive iodine, and surgery— often result in significant side effects, incomplete remissions, and frequent relapses. Further, current first-line treatment options focus on symptoms management, and reflect an inadequate understanding of the etiology of the condition. However, recent research reveals a […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This original investigation employed a two‑sample Mendelian randomization (MR) framework to test whether genetically predicted variation in gut microbiota (GM) composition exerts causal effects on six thyroid diseases (TDs): nontoxic diffuse goiter (NDG), nontoxic multinodular goiter (NMG), nontoxic single thyroid nodule (NSTN), Graves’ disease (GD), Plummer disease (PD) and thyrotoxicosis with toxic single thyroid nodule (TSTN). Genome‑wide association study (GWAS) summary statistics for 119 genera (1,531 SNPs) served as exposures, while disease outcomes were derived from large population‑based GWAS datasets. IVW was the primary MR method, complemented by weighted median, MR‑Egger, and sensitivity checks for heterogeneity and pleiotropy.
Who was studied?
GM data originated from the MiBioGen consortium (18,340 primarily European participants), and thyroid phenotypes came from FinnGen Release 10 (906–6,699 cases and ≥ 349,000 controls per phenotype, all of European ancestry). Thus, the analytic sample represents adult Europeans with genotyped data and harmonized microbial and thyroid phenotypes.
Most important findings
MR identified 32 genera with putative causal links to TDs. Protective associations included Clostridium innocuum group, Ruminiclostridium 5 and Lachnoclostridium for NDG (OR ≈ 0.59–0.72), Bifidobacterium and Sutterella for NMG (OR ≈ 0.77–0.83), and Ruminiclostridium 9, Victivallis and Butyricimonas for GD (OR ≈ 0.75–0.85). Conversely, taxa such as Alistipes, Methanobrevibacter, Ruminococcaceae UCG014 (NDG), Ruminococcus gauvreauii group and Rikenellaceae RC9 (NMG), Eubacterium rectale group and Desulfovibrio (GD), and Dorea, Eggerthella and Phascolarctobacterium (PD) increased disease risk (OR 1.2–2.3). For TSTN, Parasutterella was protective, whereas Sutterella, Oscillibacter and Clostridium sensu stricto 1 conferred marked risk (OR ~ 2–3.4).
Key implications
These results strengthen the concept of a gut–thyroid axis by demonstrating genus‑level causal effects, not mere correlations. Protective genera often produce short‑chain fatty acids (e.g., butyrate), enhance epithelial barrier integrity and modulate T‑cell differentiation, whereas risk genera have pro‑inflammatory or lipopolysaccharide (LPS)‑rich profiles. Clinically, microbiome‑targeted interventions (MBTIs) such as fiber supplementation, next‑generation probiotics or microbiota‑directed drugs may complement iodine optimisation and immunomodulation for TD prevention or adjunctive therapy. However, the findings pertain to European ancestry and genus‑level resolution; host–microbe–immune interactions and sex‑specific effects warrant validation in multi‑ethnic, mechanistic, and longitudinal cohorts.
Lipopolysaccharide (LPS)
Lipopolysaccharide (LPS), a potent endotoxin present in the outer membrane of Gram-negative bacteria that causes chronic immune responses associated with inflammation.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Probiotics
Probiotics are live microorganisms that offer significant health benefits when administered in adequate amounts. They primarily work by modulating the gut microbiome, supporting a balanced microbial ecosystem. Probiotics have been shown to improve gut health, modulate immune responses, and even influence metabolic and mental health disorders. With growing evidence supporting their therapeutic potential, probiotics are increasingly recognized for their role in treating conditions like irritable bowel syndrome (IBS), antibiotic-associated diarrhea (AAD), and even mental health conditions like depression and anxiety through their impact on the gut-brain axis.