Objectives: Variations of gut microbiota composition have been described in patients with different thyroid disorders. The site of oral levothyroxine (T4) absorption is represented by the small intestine and it has been demonstrated that some bacterial strains possess enzymatic activity that may affect iodothyronine deconjugation, process probably involved in thyroid hormone enterohepatic recycling. The relationship between gut microflora composition and oral T4 requirement has, as yet, not been analyzed, and represents the aim of the present study.
Patients and Methods: Twenty two hypothyroid adult patients (19F/3M) treated with oral levothyroxine at a stable dose for at least two years, have been subdivided into two groups on the basis of their T4 requirement: A) group, showing an increased need for T4 (10 patients; 9F/1M; median dose 1.76 mg/kg/day) or a normal one, B) group (12 patients; 10F/2M; median dose 1.36 mg/kg/day). All patients had TSH values between 0.8 and 2 mU/l. All patients took T4 in fasting state, avoiding all food and drugs interfering with T4 absorption and action. Moreover, none of included patients followed unbalanced diets, had disorders, or used drugs, interfering with faecal microbial composition. From each patient faecal samples were provided. Microbiota composition was determined via 16s rDNA sequencing of the hypervariable region V3-4 on Illumina MiSeq. Alpha and beta-diversity indices and all statistical analysis were computed in Qiime2.
Results: Alpha-diversity indices showed an increased relative abundance of Firmicutes in BEN group while an increased relative abundance of Bacteroidetes and Proteobacteria characterized MAL group. Beta-diversity analysis, revealed a significant difference between the microbial populations of patients belonging to the two groups through weighted UniFrac analysis (P = 0.008). The ANalysis of COmposition of Microbiomes (ANCOM) between the different taxonomic units revealed that Bacteriodetes phylum is significantly associated to the increased need for T4, while Firmicutes phylum is associated to a normal T4 absorption. The Linear discriminant analysis with Effect Size measurement (LEfSe) allowed the identification of potential biomarkers associated to the increased need for T4, mostly belonging to the class of beta-Proteobacteria.
Conclusions: Despite the low number of patients, typical of a pilot study, this is the first characterization of faecal microbiota composition of hypothyroid patients with the specific focus on T4 requirement.
10 Sep 2022 - 13 Sep 2022