Immunomodulatory Effects of Lactobacillus brevis NES-428 in a Hyperthyroidism Mouse Model: Potential Applications for Graves' Disease

초록

Background: Safe, microbiome-based interventions for autoimmune hyperthyroidism are lacking. We isolated the lactic acid bacterium NES-428 from kimchi and previously demonstrated that it shares 99% 16S-rRNA identity with Lactobacillus brevis reference strains, confirming NES-428 as a novel strain. Here we evaluated its immunomodulatory and anti-thyroid activity in cellular and murine models. Methods: Jurkat T cells (5 x 10(6)) were incubated with heat-killed NES-428 for 24 h and subsequently stimulated with phorbol 12-myristate 13-acetate/ionomycin (50 ng mL(-1)/1 mu g mL(-1)) for 6 h; cytokine transcripts were quantified by qRT-PCR. Hyperthyroidism was induced in female BALB/c mice by three intramuscular injections of adenovirus-encoding human TSH receptor (Ad-TSHR). Mice received a daily oral dose of NES-428 (1 x 10(9) CFU) for 15 weeks. Serum thyroxine (T-4) levels, splenocyte cytokine secretion, and thyroid histopathology were assessed. Statistical analyses employed one-way ANOVA with Tukey post hoc or log-rank tests (alpha = 0.05). Results: NES-428 pre-conditioning of Jurkat cells significantly down-regulated IL-2 and IFN-gamma transcripts (-48% and -43%, respectively; p < 0.01) compared with stimulated controls while modestly increasing IL-4 (+26%). In Ad-TSHR mice, daily NES-428 reduced mean serum T-4 from 11.2 +/- 2.1 to 5.8 +/- 1.4 <mu>g dL(-1) (p < 0.001), restored body weight gain, and normalized follicular architecture relative to untreated hyperthyroid animals. NES-428 supplementation also lowered splenocyte IFN-gamma secretion by 58% and raised IL-4 by 41% (p < 0.05). Conclusions: The kimchi-derived strain NES-428 attenuates Th1-skewed cytokine responses and ameliorates experimental hyperthyroidism in vivo. These findings support further investigation of NES-428 as a probiotic candidate for immune modulation in Graves' disease.

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