Gut Microbes Linked to Hypothyroidism: Study Finds Causal Associations

In a recent publication in Frontiers in Nutrition, scholars delved into the correlation between the microbial composition of the intestinal tract and hypothyroidism. Background Hypothyroidism, a hormonal disparity marked by reduced activity of the thyroid gland and inadequate synthesis of thyroid hormones, may precipitate heart conditions, infertility, and impaired cognitive development in juveniles.

It bears significant economic and societal repercussions on affected individuals. Investigations have suggested that the gut microbiota could indirectly impact thyroid function. Studies have indicated a decline in Prevotella levels in patients with hypothyroidism and an elevation in Phascolarctobacterium, culminating in diminished bacterial diversity and abundance.

Intestinal microorganisms generate short-chain fatty acids (SCFAs), which regulate the expression of thyroid cells and preserve the integrity of the intestinal barrier. Inadequate iodine intake stands as a leading cause of hypothyroidism, as the gut flora modulates mineral absorption and enzyme function in thyroid hormone synthesis.

Nevertheless, the precise nexus between gut microbes and hypothyroidism remains elusive, attributed to historical case-control studies and confounding factors such as age, environment, diet, and lifestyle.

Comprehending the linkage between the gut microbiome and hypothyroidism necessitates extensive exploration of the underlying mechanisms and the formulation of innovative therapeutic interventions. About the Study In this study, researchers employed a two-sample and bidirectional Mendelian randomization (MR) to investigate whether gut microbes play a causal role in the onset of hypothyroidism.

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

Instrumental variables (IVs) were meticulously chosen from the MiBioGen consortium dataset, focusing on SNPs associated with gut microbial composition, with IV heterogeneity assessed using Cochran’s Q statistics.

Various methodologies were employed by the team, including the weighted median, MR-Egger, simple model, weighted model, inverse variance weighted (IVW), and MR-PRESSO, to ascertain the potential causal link between gut microbes and hypothyroidism.

Furthermore, reverse MR assessments were conducted for microbes exhibiting causal associations with hypothyroidism in the forward MR evaluation. Sensitivity analysis involved the examination of horizontal pleiotropy and a leave-one-out analysis.

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

Microbiome quantitative trait loci (mbQTL) were mapped to identify genetic variants associated with specific loci linked to gut bacteria. At the genus level, the researchers scrutinized 119 taxa, utilizing 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.

Conversely, Anaerostipes species (odds ratio 1.2), Intestinimonas species (odds ratio 1.1), and Ruminiclostridium species (odds ratio 1.2) were found to be deleterious in relation to hypothyroidism.

Reverse MR estimates revealed no significant effects of hypothyroidism on the gut microbiome. Cochran’s Q statistics indicated no significant heterogeneity among instrumental variables. Sensitivity analyses demonstrated non-significant horizontal pleiotropy, with no SNPs significantly affecting the relationship between gut microbes and hypothyroidism.

Akkermansia, renowned for fortifying the intestinal lining, enhancing the mucus layer, and modulating the immune system, holds promise as a probiotic or live biotherapeutic product therapy. Its role in intestinal repair and immunomodulation offers new avenues for hypothyroidism prevention and treatment.

Butyrivibrio bacteria, responsible for breaking down plant fibers and producing butyric acid, contribute to the generation of SCFAs and promotion of intestinal health, potentially impacting hypothyroidism.

Holdemania has been linked to various disorders, including Parkinson’s disease and delirium. Hypothyroidism, characterized by diminished thyroid hormone levels, may manifest neuropsychiatric symptoms.

Excessive alcohol consumption correlates with increased levels of Holdemania in the gastrointestinal tract, consequently reducing butyric acid concentration.

Anaerostipes, specialized anaerobes producing acetic and butyric acids, were found to potentially exacerbate hypothyroidism.

This finding may be attributed to confounding factors such as age, sex, ethnicity, dietary habits, and medications. Hypothyroidism can result in impaired gastrointestinal motility and overgrowth of intestinal flora, potentially influencing Anaerostipes abundance during recovery.

The study unveiled causal associations between Akkermansia species and hypothyroidism, with elevated Akkermansia levels linked to reduced incidence and progression.

The identification of probiotics such as Akkermansia, Holdemania, Ruminococcaceae UCG-011, and Butyrivibrio, which confer protection against hypothyroidism, contrasts with the adverse effects observed with Intestinimonas, Anaerostipes, and Ruminiclostridium. However, further randomized clinical trials are imperative to elucidate precise mechanisms for targeted personalized therapies, enhancing precision care.

For more information: Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study, Frontiers in Nutrition, https://doi.org/10.3389/fnut.2024.1286593