Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis

Clin Sci (Lond). 2020 Jun 26;134(12):1521-1535. doi: 10.1042/CS20200475.

Abstract

Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.

Keywords: Fecal microbiota transplantation; Gut microbiome; Lipopolysaccharides; Primary hypothyroidism; Receiver operator characteristic curve; Short chain fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Case-Control Studies
  • Dysbiosis / complications*
  • Fatty Acids / metabolism
  • Fecal Microbiota Transplantation
  • Female
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / pathology*
  • Humans
  • Hypothyroidism / complications*
  • Male
  • Metagenomics
  • Mice, Inbred BALB C
  • Phylogeny
  • ROC Curve
  • Thyroid Gland / pathology*

Substances

  • Fatty Acids