The gut microbiota plays an important role in multifaceted physiological functions in the host. Previous studies have assessed the probiotic effects of Lactobacillus salivarius LI01. In this study, we aimed to investigate the potential effects and putative mechanism of L. salivarius LI01 in immune modulation and metabolic regulation through the monocolonization of germ-free (GF) Sprague-Dawley (SD) rats with L. salivarius LI01. The GF rats were separated into two groups and administered a gavage of L. salivarius LI01 or an equal amount of phosphate-buffered saline. The levels of serum biomarkers, such as interleukin (IL)-1α, IL-5, and IL-10, were restored by L. salivarius LI01, which indicated the activation of Th0 cell differentiation toward immune homeostasis. L. salivarius LI01 also stimulated the immune response and metabolic process by altering transcriptional expression in the ileum and liver. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of the 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which indicated that L. salivarius LI01 exerts an effect on energy accumulation. The LI01 group showed alterations in fecal carbohydrates accompanied by an increased body weight gain. In addition, L. salivarius LI01 produced indole-3-lactic acid (ILA) and enhanced arginine metabolism by rebalancing the interconversion between arginine and proline. These findings provide evidence showing that L. salivarius LI01 can directly impact the host by modulating immunity and metabolism.
• Lactobacillus salivarius LI01 conventionalizes the cytokine profile and activates the immune response.
• LI01 modulates carbohydrate metabolism and arginine transaction.
• LI01 generates tryptophan-derived indole-3-lactic acid.
• The cytochrome P450 family contributes to the response to altered metabolites.
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We would like to thank Yongjun Li and Yifeng Gu at the State Key Laboratory for Diagnosis, National Clinical Research Center for Infectious Diseases for their contribution to the maintenance of the germ-free rats. We would like to thank Ping Yang at the Center of Cryo-Electron Microscopy (CCEM) at Zhejiang University for the technical assistance provided with the transmission electron microscopy.
This study was funded by the National Natural Science Foundation of China (81790631, 81570512), the National Key Research and Development Program of China (2018YFC2000500) and the Natural Science Foundation of Zhejiang Province, China (LQ19H030007).
Conflicts of interest
The authors declare that they have no conflict of interest.
All procedures were performed according to the 2011 National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University (permit no. 2019-1088).
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All the participants included in this study provided written informed consent prior to sample collection. The research is in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board of the First Affiliated Hospital of Zhejiang University.
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Xia, J., Jiang, S., Lv, L. et al. Modulation of the immune response and metabolism in germ-free rats colonized by the probiotic Lactobacillus salivarius LI01. Appl Microbiol Biotechnol 105, 1629–1645 (2021). https://doi.org/10.1007/s00253-021-11099-z
- Gut microbiota
- Immune homeostasis
- Germ-free model
- Lactobacillus salivarius