Relationship between hypothyroidism, risk of small intestinal bacterial overgrowth, and duodenal microbiome alterations.

There is an association between hypothyroidism and small intestinal bacterial overgrowth (SIBO), but the exact mechanistic link between these two conditions is not fully elucidated. We evaluate the incidence and risks of subsequently developing SIBO, and changes in small bowel microbial populations, in subjects with hypothyroidism or autoimmune thyroiditis. Duodenal aspirates from REIMAGINE study subjects with a history of hypothyroidism (hypothyroid group, N=49) and controls (N=323) underwent 16S rRNA sequencing (MiSeq, Illumina); a subset also underwent metagenomic sequencing (NovaSeq6000, Illumina). Separately, the TriNetX Analytics platform was used to evaluate ten-year cumulative incidences and relative risk [RR] of developing SIBO in subjects with hypothyroidism (unspecified etiology, HUE), and a subset with autoimmune thyroiditis, vs. propensity score matched (PSM) control groups. Among REIMAGINE subjects, SIBO prevalence was higher in the hypothyroid group (32.65%) vs. controls (15.17%). In the TriNetX analysis, ten-year cumulative incidences of SIBO were higher in HUE (RR=2.20) and autoimmune thyroiditis (RR=2.40) subjects vs. matched controls. However, these risks appeared to be mitigated both in HUE (RR=0.33) and autoimmune thyroiditis (RR=0.78) subjects taking levothyroxine. Analyzing the duodenal microbiome, genus Neisseria was part of the core microbiome in the hypothyroid group (Hypo+/SIBO-, Hypo+/SIBO+) but not in non-hypothyroid subjects (Hypo-/SIBO-, Hypo-/SIBO+). Increased prevalence of Gram-negative coliforms occurred in both SIBO+ groups, but Escherichia/Shigella formed part of the core in non-hypothyroid subjects (Hypo-/SIBO+), whereas Klebsiella species were prevalent in hypothyroid group subjects with SIBO (Hypo+/SIBO+). These findings suggest there is an increased risk for development of SIBO in individuals with a history of hypothyroidism which may be ameliorated by treatment, and may involve specific Gram-negative coliforms.