Abstract
The Rosalind Franklin Society (RFS), in partnership with Mary Ann Liebert, Inc., publishers, enthusiastically congratulate our distinguished recipient of the 2023 annual
Aline C. Fenneman, Eveline Bruinstroop, Max Nieuwdorp, Anne H. van der Spek, and Anita Boelen, “A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications,” Thyroid 33, no. 1 (January 2023): 32–44, https://doi.org/10.1089/thy.2022.0491.
Abstract
Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation.
Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto’s thyroiditis, Graves’ disease, and Graves’ orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed.
Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis.
Biosketch
Anita Boelen, PhD, is a Professor of Thyroid Hormone Metabolism, in particular molecular and diagnostic aspects, in the Endocrine Laboratory at the Amsterdam University Medical Center, University of Amsterdam. She received a PhD in Thyroid Hormone Metabolism from the University of Amsterdam (Department of Endocrinology, AMC). She is a basic scientist with a research focus on thyroid hormone metabolism in innate immune cells and on mechanisms involved in congenital central hypothyroidism. She has published more than 150 peer-reviewed publications as well as several book chapters.
Anita Boelen is also head of the regional Dutch Neonatal Screening program at the Endocrine Laboratory and responsible for the measurements in heel prick blood of neonates born in the region Noord Holland and Flevoland (in total appr. 36.000 neonates/year). She is a member of the advisory board Neonatal screening CH/AGS, this board evaluates the neonatal screening on CH and AGS and advises the National Institute of Health.