Exploring the gut-thyroid axis The role of the microbiome in thyroid autoimmunity

The autoimmune thyroid diseases Hashimoto's thyroiditis and Graves' disease have become increasingly prevalent in recent years. Through a multifaceted approach encompassing a thorough literature review, an epidemiological study, a randomized clinical trial, and fundamental research, the thesis sheds new light on the compelling bidirectional communication of the gut-thyroid axis. This thesis investigates how thyroid hormones can affect gut homeostasis. As such, the effect of oral levothyroxine administration on gut homeostasis, including colorectal tumor growth, is explored. A population-based case-control study reveals limited evidence of reduced colorectal cancer risk among levothyroxine users.
The second part focuses on gut microbiota's influence on Hashimoto's thyroiditis. The previous studies observed compositional shifts in the gut microbiome, yet inconsistencies in microbiome signatures hinder definitive conclusions. The IMITHOT study explores the effect of multiple fecal microbiota transplantations (FMT) as a treatment modality for autoimmune hypothyroidism, which comes with a cost-intensive screening of healthy stool donors. With the results of the IMITHOT trial still pending, it can only be speculated about the potential for personalized treatment of autoimmune thyroid disease. Subsequently, an increased intestinal permeability was shown in Graves’ disease patients compared to healthy individuals, leading to systemic inflammation and potentially aggravating the inflammatory processes within the orbital tissue, including fibrosis.
Finally, the significance of early-life microbiome perturbations and the potential long-term implications emphasize the need for judicious antibiotic use. To conclude, the findings of this thesis contribute to an enhanced understanding of the complex interactions between the gut and thyroid, paving the way for further exploration in this emerging field of research.