Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor

Abstract Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host’s immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 (L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clea...

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Main Authors: Zikang Zhang, Kangdi Zheng, Zhao Zhang, Longbin Cao, Lizhu Lin, Weimin Sun, Feng Qiu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Microbial Cell Factories
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Online Access:https://doi.org/10.1186/s12934-025-02662-8
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author Zikang Zhang
Kangdi Zheng
Zhao Zhang
Longbin Cao
Lizhu Lin
Weimin Sun
Feng Qiu
author_facet Zikang Zhang
Kangdi Zheng
Zhao Zhang
Longbin Cao
Lizhu Lin
Weimin Sun
Feng Qiu
author_sort Zikang Zhang
collection DOAJ
description Abstract Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host’s immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 (L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clearance of HPV infection and beneficially regulate immune response. However, the mechanisms behind the regulation of L. gasseri LGV03 in immune response remain unclear. To better understand the interaction between female genital tract microbiome and immune function, the immunomodulatory activities of L. gasseri LGV03 were investigated in zebrafish models of neutropenia, macrophage and T cells deficiency. L. gasseri LGV03 showed higher potent activities in ameliorating vinorelbine-induced neutropenia, macrophage and T cells deficiency, and significantly enhanced mRNA expressions of cytokines TNF-α, TNF-β and IFN-α. Moreover, the transcriptome sequencing results indicated L. gasseri LGV03 might alleviate vinorelbine-induced immunosuppression in zebrafish. Non-targeted detection and analysis revealed that indole derivatives including phenylacetaldehyde, 3-phenyllactic acid, N-acetylserotonin and indole-3-lactic acid were significantly increased in the lysate and supernatant of L. gasseri LGV03. Meanwhile, L. gasseri LGV03 supernatant and indole-3-lactic acid ameliorated the vinorelbine-induced reduction in abundance of macrophages, neutrophils and T cells. However, the alleviating effects of L. gasseri LGV03 supernatant or indole-3-lactic acid were eliminated by aryl hydrocarbon receptor (AHR) antagonist CH-223,191. Furthermore, L. gasseri LGV03 supernatant and indole-3-lactic acid significantly increased the secretion of IFN-α, IFN-β and chemokines (MIP-1α, MIP-1β) in Ect1/E6E7 cells, meanwhile, these benefits were eliminated by CH-223,191 treatment. In summary, L. gasseri LGV03-derived indole-3-lactic acid can activate AHR-mediated immune response.
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issn 1475-2859
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spelling doaj-art-0bc1ee163c34493d91ea1b941e5671912025-02-02T12:48:37ZengBMCMicrobial Cell Factories1475-28592025-01-0124111410.1186/s12934-025-02662-8Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptorZikang Zhang0Kangdi Zheng1Zhao Zhang2Longbin Cao3Lizhu Lin4Weimin Sun5Feng Qiu6Department of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical UniversityResearch and Development Department, Guangdong Longseek Testing Co., Ltd.Research and Development Department, Guangdong Longseek Testing Co., Ltd.Department of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical UniversityDepartment of General Practice Center, The Seventh Affiliated Hospital of Southern Medical UniversityDepartment of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical UniversityDepartment of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical UniversityAbstract Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host’s immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 (L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clearance of HPV infection and beneficially regulate immune response. However, the mechanisms behind the regulation of L. gasseri LGV03 in immune response remain unclear. To better understand the interaction between female genital tract microbiome and immune function, the immunomodulatory activities of L. gasseri LGV03 were investigated in zebrafish models of neutropenia, macrophage and T cells deficiency. L. gasseri LGV03 showed higher potent activities in ameliorating vinorelbine-induced neutropenia, macrophage and T cells deficiency, and significantly enhanced mRNA expressions of cytokines TNF-α, TNF-β and IFN-α. Moreover, the transcriptome sequencing results indicated L. gasseri LGV03 might alleviate vinorelbine-induced immunosuppression in zebrafish. Non-targeted detection and analysis revealed that indole derivatives including phenylacetaldehyde, 3-phenyllactic acid, N-acetylserotonin and indole-3-lactic acid were significantly increased in the lysate and supernatant of L. gasseri LGV03. Meanwhile, L. gasseri LGV03 supernatant and indole-3-lactic acid ameliorated the vinorelbine-induced reduction in abundance of macrophages, neutrophils and T cells. However, the alleviating effects of L. gasseri LGV03 supernatant or indole-3-lactic acid were eliminated by aryl hydrocarbon receptor (AHR) antagonist CH-223,191. Furthermore, L. gasseri LGV03 supernatant and indole-3-lactic acid significantly increased the secretion of IFN-α, IFN-β and chemokines (MIP-1α, MIP-1β) in Ect1/E6E7 cells, meanwhile, these benefits were eliminated by CH-223,191 treatment. In summary, L. gasseri LGV03-derived indole-3-lactic acid can activate AHR-mediated immune response.https://doi.org/10.1186/s12934-025-02662-8Lactobacillus gasseri LGV03Immune responseActivating aryl hydrocarbon receptorIndole-3-lactic acid
spellingShingle Zikang Zhang
Kangdi Zheng
Zhao Zhang
Longbin Cao
Lizhu Lin
Weimin Sun
Feng Qiu
Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
Microbial Cell Factories
Lactobacillus gasseri LGV03
Immune response
Activating aryl hydrocarbon receptor
Indole-3-lactic acid
title Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
title_full Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
title_fullStr Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
title_full_unstemmed Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
title_short Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
title_sort lactobacillus gasseri lgv03 derived indole 3 lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
topic Lactobacillus gasseri LGV03
Immune response
Activating aryl hydrocarbon receptor
Indole-3-lactic acid
url https://doi.org/10.1186/s12934-025-02662-8
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