Comparative genomic insights into strain-specific zinc-promoting effects of the spore-forming probiotic Heyndrickxia coagulans.

Authors

Yuxuan Qiu, Chengcheng Zhang, Enduo Ma, Xia Zheng, Rong Wang, Qianqian Li, Nuo Li, Gang Wang, Shumao Cui, Wenwei Lu, Bo Yang, Xiaomei Lv, Jianxin Zhao, Wei Chen, Qixiao Zhai

Published in

Food & function. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Zinc deficiency is a prevalent micronutrient disorder, and probiotic intervention has emerged as a promising strategy to improve zinc bioavailability. However, the strain-specific characteristics and genetic basis underlying the zinc-promoting effects of probiotics remain poorly understood. Therefore, this study aimed to identify the key physiological properties and functional genes associated with the zinc-promoting capacity of Heyndrickxia coagulans (H. coagulans, formerly Bacillus coagulans). A Caco-2 intestinal epithelial cell monolayer model and a zinc-deficient mouse model were established to evaluate the zinc-promoting effects of H. coagulans. Male BALB/c mice were fed a zinc-deficient diet and orally administered H. coagulans spores (10⁷ CFU per mouse per day) combined with zinc gluconate (0.15 mg Zn per mouse per day) for 4 weeks. Serum zinc concentration, alkaline phosphatase activity, organ indices, and intestinal zinc homeostasis-related gene expression were evaluated. Furthermore, comparative genomic analysis was performed to identify candidate genomic features potentially associated with strain-dependent differences in zinc-promoting capacity. Among the tested strains, H. coagulans CCFM1539, CCFM1540, and CCFM1541 exhibited distinct zinc-promoting capacities. In vitro, CCFM1539 significantly enhanced zinc transmembrane transport and modulated the transcription of zinc transporter genes. In vivo, supplementation with H. coagulans spores combined with zinc gluconate more effectively restored serum zinc concentration, alkaline phosphatase activity, organ indices, and intestinal zinc homeostasis-related gene expression (Zip4, Znt1, Znt2, and Vdr) than zinc supplementation alone. Notably, CCFM1541 showed the strongest overall zinc-promoting phenotype, with superior restoration of serum zinc concentration and Vdr expression. Comparative genomic analysis revealed that strain-specific zinc-promoting effects were associated with genes involved in ion transport, stress adaptation, carbohydrate metabolism, and cellular regulation. Among the CCFM1541-specific genes, ABC transporter-related genes, particularly gsiB, gsiC, gsiD, oppD, and oppF, were identified as candidate genes potentially associated with its superior zinc-promoting phenotype. In conclusion, the zinc-promoting effects of H. coagulans are strain-specific and are associated with changes in intestinal zinc homeostasis and bacterial genomic features. These findings provide genomic insights into probiotic-mediated mineral bioavailability and identify candidate genes for future functional validation.

PMID:
42825603
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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