The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice

Pol J Microbiol. 2023 Dec 16;72(4):443-460. doi: 10.33073/pjm-2023-042. eCollection 2023 Dec 1.

Abstract

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

Keywords: Graves’ disease; Lactobacillus; gut microbiota; pyrroloquinoline quinone; thyroid function.

MeSH terms

  • Animals
  • Gastrointestinal Microbiome* / physiology
  • Graves Disease* / drug therapy
  • Graves Disease* / genetics
  • Mice
  • PQQ Cofactor
  • Receptors, Thyrotropin / genetics

Substances

  • PQQ Cofactor
  • Receptors, Thyrotropin

Grants and funding

This work was supported by the [National Natural Science Foundation of China] under Grant [number 82071964], [Shanghai Shenkang Three-year Action Project] under Grant [number SHDC-2020CR2054B], [Shanghai Leading Talent Program sponsored by Shanghai Human Resources and Social Security Bureau] under Grant [number 03.05.19005], and [Key discipline construction project of the three-year action plan of Shanghai public health system] under Grant [number GWV-10.1-XK9].