Study highlights causal associations between gut microbes and hypothyroidism

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In a recent study published in Frontiers in Nutrition, researchers explored the association between the microbial community of the gut and hypothyroidism.

Study: Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study. Image Credit: sdecoret/Shutterstock.comStudy: Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study. Image Credit: sdecoret/Shutterstock.com

Background

Hypothyroidism is a hormonal imbalance characterized by diminished thyroid gland activity and insufficient thyroid hormone synthesis, which can lead to heart disease, infertility, and poor brain development in children.

It has a tremendous economic and social impact on the individuals impacted. Research has revealed that the gut microbiome might indirectly influence thyroid function, with studies indicating a drop in Prevotella in hypothyroid patients and an increase in Phascolarctobacterium, resulting in decreased bacterial diversity and richness.

Gut microorganisms create short-chain fatty acids (SCFAs), which control thyroid cell expression and keep the intestinal barrier intact. Inadequate iodine consumption is a major cause of hypothyroidism, as the gut flora influences mineral absorption and enzyme activity in thyroid hormone production.

However, the precise relationship between gut microbes and hypothyroidism is unknown due to historical case-control studies and confounding variables such as age, environment, nutrition, and lifestyle.

Understanding the association between the intestinal microbiome and hypothyroidism requires extensive research into the underlying reasons and the development of novel therapeutic options.

About the study

The present two-sample and bidirectional Mendelian randomization (MR) researchers investigated whether gut microbes causally affect hypothyroidism development.

The team analyzed summary statistical data from genome-wide association studies (GWAS) provided by the FinnGen [26,342 hypothyroidism cases of hypothyroidism with 59,827 controls; 16,378,441 single-nucleotide polymorphisms (SNPs)] and MiBioGen consortia (n = 18,430).

They selected instrumental variables (IVs) from the MiBioGen consortium dataset, targeting SNPs related to gut microbial composition and gauging IV heterogeneity using Cochran's Q statistics.

The team used several techniques, including the weighted median, MR-Egger, simple model, weighted model, inverse variance weighted (IVW), and MR-PRESSO, to determine whether gut microbes are causally associated with hypothyroidism.

They also performed reverse MR assessments for microbes that showed causal associations with hypothyroidism development in forward MR evaluation. For sensitivity analysis, they assessed horizontal pleiotropy and performed a leave-one-out analysis.

The researchers analyzed the 16S ribosomal ribonucleic acid (rRNA) gene variable sites V1-V2, V3-V4, and V4 to assess gut microbial abundances and taxonomic classifications by direct-type taxonomic binning.

They mapped microbiome quantitative trait loci (mbQTL) to detect genetic variants related to specific loci associated with gut bacteria. The researchers analyzed 119 taxa at the genus level, using 1,231 single-nucleotide polymorphisms as instrumental variables for assessment.

Results and discussion

In the IVW analysis, Akkermansia species (odds ratio 0.8), Ruminococcaceae UCG-011 isolate (odds ratio 0.9), Butyrivibrio species (odds ratio 0.9), and Holdemania species (odds ratio 0.9) exhibited protective effects against hypothyroidism.

In contrast, Anaerostipes species (odds ratio 1.2), Intestinimonas species (odds ratio 1.1), and Ruminiclostridium species (odds ratio 1.2) were detrimental to hypothyroidism.

Reverse MR estimates indicated no significant effects of hypothyroidism on the gut microbiome. Cochran’s Q statistics showed no significant heterogeneity among instrumental variables. The sensitivity analyses demonstrated the non-significant horizontal pleiotropy, and no SNPs considerably impacted the relationship between gut microbes and hypothyroidism.

Akkermansia, a gut microbe that strengthens the intestinal lining, boosts the mucus layer and regulates the immune system, is a promising probiotic or live biotherapeutic product therapy. Its intestinal repair and immunomodulatory functions may provide new insights into hypothyroidism prevention and treatment.

Butyrivibrio bacteria, which break down plant fibers and produce butyric acid, can generate SCFAs and promote intestinal well-being, which may be a significant factor in hypothyroidism.

Holdemania is associated with several illnesses, including Parkinson's disease and delirium. Hypothyroidism, characterized by reduced thyroid hormone levels, can lead to neuropsychiatric symptoms.

Excessive alcohol consumption is associated with elevated levels of Holdemania in the gastrointestinal tract, reducing butyric acid concentration.

The results indicated that anaerostipes, specialized anaerobes producing acetic and butyric acids, may contribute to hypothyroidism.

The finding may be due to confounding factors like age, sex, ethnicity, dietary habits, and medications. Hypothyroidism can cause impaired gastrointestinal motility and overgrowth of intestinal flora, potentially altering Anaerostipes abundance during recovery.

The study showed causal relationships between Akkermansia species and hypothyroidism, with increased Akkermansia inhibiting incidence and progression.

The researchers identified probiotics like Akkermansia, Holdemania, Ruminococcaceae UCG-011, and Butyrivibrio that protect against hypothyroidism, while Intestinimonas, Anaerostipes, and Ruminiclostridium had contrasting effects. However, additional randomized clinical trials are required to elucidate precise mechanisms researchers can target for personalized therapies enhancing precision care.

Journal reference:
Pooja Toshniwal Paharia

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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