An oral-origin Streptococcus salivarius associated with schizophrenia reshapes intestinal T-cell immunity and promotes IL-17A-dominated inflammation
4 affiliations
- 1Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University
- 2Genome Institute, Centre for Mathematical Medicine, The First Afffliated Hospital of Xi’an Jiaotong University
- 3Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University
- 4Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University
Abstract
Background: Emerging evidence suggests that oral microbial dysbiosis contributes to neuropsychiatric disorders through microbiome–immune interactions. We previously identified an oral-origin Streptococcus salivarius enriched in individuals with schizophrenia (SCZ) and demonstrated its ability to become enriched in the intestine after oral administration. However, whether this disease-associated bacterium remodels host adaptive immunity remains unclear. Here, we investigated the effects of S. salivarius on intestinal CD4 ⁺ T-cell homeostasis and inflammatory responses.
Methods: Male C57BL/6 mice were orally administered S. salivarius for 14 days with or without prior antibiotic-mediated depletion of resident microbiota. Intestinal enrichment of S. salivarius was confirmed by quantitative PCR. Colonic lamina propria mononuclear cells (LPMCs) and mesenteric lymph node (MLN) cells were analyzed using single-cell RNA sequencing and flow cytometry to characterize CD4 ⁺ T cell responses. Cytokine levels in colon tissues and serum were quantified by ELISA.
Results: Single-cell transcriptomic analysis demonstrated that intestinal enrichment of S. salivarius altered Treg-associated transcriptional programs, with reduced Treg-stability signatures and increased Type-17-associated features. Flow cytometry confirmed increased Th17 cells, reduced Treg frequencies, and disruption of intestinal Th17/Treg homeostasis. Similar immune alternations were observed in MLNs, indicating extension of gut-associated immune remodeling beyond the intestinal mucosa. S. salivarius exposure was further associated with selective IL-17A in colonic tissues and serum, whereas IL-6, IL-1β, IL-10, and TGF-β remained largely unchanged. Comparable immune changes were observed in both antibiotic-pretreated and conventional SPF mice, indicating that these immunological effects were not restricted to microbiota-depletion condition.
Discussion: These findings identify an SCZ-associated oral-origin S. salivarius as a modulator of intestinal adaptive immunity. Intestinal enrichment of S. salivarius was associated with coordinated remodeling of Treg-associated transcriptional programs, Th17-biased immune polarization, and an IL-17A-dominated inflammatory response, Together, these results define an intestinal immune mechanism through which a disease-associated oral bacterium may contribute to oral-gut immune interactions and provide experimental support for one immunological component of the oral-gut-brain axis relevant to schizophrenia.
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BibTeX
@article{kang2026oralorigin,
title = {{An oral-origin Streptococcus salivarius associated with schizophrenia reshapes intestinal T-cell immunity and promotes IL-17A-dominated inflammation}},
author = {Yongyong Kang and Yajuan Fan and Qingyan Ma and Lu Yu and Jing Liu and Yixin Liu and Ziyang Zhou and Huanhuan Zhao and Zai Yang and Yufeng Xun and Min Jia and Binbin Zhao and Xiancang Ma and Wei Wang and Yijie Guo},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1978713},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978713/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An oral-origin Streptococcus salivarius associated with schizophrenia reshapes intestinal T-cell immunity and promotes IL-17A-dominated inflammation
AU - Yongyong Kang
AU - Yajuan Fan
AU - Qingyan Ma
AU - Lu Yu
AU - Jing Liu
AU - Yixin Liu
AU - Ziyang Zhou
AU - Huanhuan Zhao
AU - Zai Yang
AU - Yufeng Xun
AU - Min Jia
AU - Binbin Zhao
AU - Xiancang Ma
AU - Wei Wang
AU - Yijie Guo
PY - 2026
DA - 2026/10/15
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1978713
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978713/full
AB - Background: Emerging evidence suggests that oral microbial dysbiosis contributes to neuropsychiatric disorders through microbiome–immune interactions. We previously identified an oral-origin Streptococcus salivarius enriched in individuals with schizophrenia (SCZ) and demonstrated its ability to become enriched in the intestine after oral administration. However, whether this disease-associated bacterium remodels host adaptive immunity remains unclear. Here, we investigated the effects of S. salivarius on intestinal CD4 ⁺ T-cell homeostasis and inflammatory responses. Methods: Male C57BL/6 mice were orally administered S. salivarius for 14 days with or without prior antibiotic-mediated depletion of resident microbiota. Intestinal enrichment of S. salivarius was confirmed by quantitative PCR. Colonic lamina propria mononuclear cells (LPMCs) and mesenteric lymph node (MLN) cells were analyzed using single-cell RNA sequencing and flow cytometry to characterize CD4 ⁺ T cell responses. Cytokine levels in colon tissues and serum were quantified by ELISA. Results: Single-cell transcriptomic analysis demonstrated that intestinal enrichment of S. salivarius altered Treg-associated transcriptional programs, with reduced Treg-stability signatures and increased Type-17-associated features. Flow cytometry confirmed increased Th17 cells, reduced Treg frequencies, and disruption of intestinal Th17/Treg homeostasis. Similar immune alternations were observed in MLNs, indicating extension of gut-associated immune remodeling beyond the intestinal mucosa. S. salivarius exposure was further associated with selective IL-17A in colonic tissues and serum, whereas IL-6, IL-1β, IL-10, and TGF-β remained largely unchanged. Comparable immune changes were observed in both antibiotic-pretreated and conventional SPF mice, indicating that these immunological effects were not restricted to microbiota-depletion condition. Discussion: These findings identify an SCZ-associated oral-origin S. salivarius as a modulator of intestinal adaptive immunity. Intestinal enrichment of S. salivarius was associated with coordinated remodeling of Treg-associated transcriptional programs, Th17-biased immune polarization, and an IL-17A-dominated inflammatory response, Together, these results define an intestinal immune mechanism through which a disease-associated oral bacterium may contribute to oral-gut immune interactions and provide experimental support for one immunological component of the oral-gut-brain axis relevant to schizophrenia.
SN - 1664-3224
ER -