Lactobacillus gasseri LGV03-derived indole-3-lactic acid ameliorates immune response by activating aryl hydrocarbon receptor
Open accessAbstract
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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Evidence suggests vaginal indoles, including ILA and indole-3-aldehyde, activate the aryl hydrocarbon receptor (AhR) to modulate immune responses and provide protection against vulvovaginal candidiasis.
“Evidence suggests that vaginal indoles, including ILA and indole-3-aldehyde, activate the aryl hydrocarbon receptor (AhR) to modulate immune responses and provide protection against vulvovaginal candidiasis [61, 62].”
From Women's health is a team effort: probiogenomics supports the development of a multi-species vaginal probiotic (2026) · cites this paper as [61]
The Conclusion reports that LGV03-derived indole-3-lactic acid (ILA) activates AhR-mediated immune responses, and the Introduction identifies indole-3-aldehyde as an AhR ligand. The paper does not show that ILA protects against vulvovaginal candidiasis; that protection appears in the title of a different study listed in its References. No page numbers are available in our copy. (LLM, conf=0.88)
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- Authors
- Zhang, Z., Zheng, K., Zhang, Z., Cao, L., Lin, L., Sun, W., & Qiu, F.
- Affiliations
- Southern Medical University (CN)
- Corresponding author
- Qiu, Feng
- Venue
- Microbial Cell Factories
- Published
- 2025-01-30
- Volume
- 24
- Issue
- 1
- Pages
- 34-34
- ISSN
- 1475-2859 (ISSN-L)
- PMC
- PMC11780890
- OpenAlex
- W4407003011
- Cited by
- 22
- References
- 39
- Citations by year
- 2026: 20 · 2025: 2
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microbial Cell Factories (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Guangdong Province (2023A1515011439)
- Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515220025)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- indole-3-lactic acid, aryl hydrocarbon receptor, immunomodulation, macrophage deficiency, T cell deficiency, cytokine expression, chemokines, CH223191, HPV clearance, zebrafish model
- MeSH terms
- Lactobacillus gasseri, Vinorelbine, Animals, Cell Line, Female, Gene Expression Regulation, Humans, Immunosuppressive Agents, Indoles, Lactobacillus, Macrophages, Neutropenia, T-Lymphocytes, Zebrafish, Cytokines, Receptors, Aryl Hydrocarbon
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