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Transcriptomic and metabolomic profiling reveals media- and host-dependent responses to <i>Staphylococcus hominis</i> in cell models.

Overview

Authors: Wenxiu Liu1,2,3, Tiansheng Zhang4, Qian Wang1,2,3, Zhunduo Li1,2,3, Yanrui Bai1,2,3, Han Xiao1,2,3, Yan Wang1,2,3, Ruihong Xiao1,2,3, Liyu Tong1,2,3, Yana Li5, Xueli Qu4, Xu Zhao6, Zhengchao Zhang7, Hui Sun1,2,3,4
  1. The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China
  2. Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China
  3. Lanzhou University, Lanzhou, China
  4. Research and Translational Center for Immunological Disorders, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
  5. Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai, China
  6. Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China
  7. Department of Urology, Yantai Affiliated Hospital of Binzhou Medical University, The Second Clinical Medical College of Binzhou Medical University, Yantai, China
Institutions: Lanzhou University Second Hospital (China); Lanzhou University (China); Binzhou Medical University (China); Chinese Academy of Agricultural Sciences (China)
Journal: PeerJ, volume 14, article e20899
Dates: received 30 June 2025; accepted 16 January 2026; published online 12 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7717/peerj.20899 · PMID 41841123 · PMCID PMC12989153 · OpenAlex W7135041364
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), cellular / molecular (subfield)
Methods: Statistics, Machine learning
Keywords: Gut-derived S. hominis, BHI and GAM media, Cell line models, Metabolome, RNA sequencing
MeSH: Culture Media*, Metabolomics*, Transcriptome*, Cell Line, Gene Expression Profiling, HEK293 Cells, Humans, Metabolome, Multiomics (* major topic)
Topic: Gut microbiota and health (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Yale University; Lanzhou University; National Natural Science Foundation of China (32070138, 82060105); National Science and Technology Major Project; Fundamental Research Funds for the Central Universities (lzujbky‐2023‐eyt04)
Citations: not cited yet (Europe PMC); 63 references in the paper

Abstract

Background/aims: Host-microbiota co-evolution maintains homeostasis via metabolic, immune, and neuroendocrine pathways. Diverse culture media and host cell models are widely used in microbiota research, but how these variables shape host transcriptional responses remains unclear. This study combined metabolomic, transcriptomic, and functional analyses to investigate how microbial culture medium and host cell type influence responses to a gut-derived Staphylococcus hominis isolate.

Methods: S. hominis was cultured for 96 h in Brain Heart Infusion (BHI) or Gifu Anaerobic Medium (GAM). Culture supernatants were collected for untargeted metabolomics and epithelial cell stimulation. Metabolomic profiling identified differentially expressed metabolites (—log2FC— >0, p < 0.05, variable importance in projection, VIP >1). RNA sequencing assessed transcriptional responses in four cell lines (MODE-K, NCM460, Henle-407, HEK-293T) treated with BHI- or GAM-derived supernatants. Differentially expressed genes (DEGs; —log2FC— >1, adjusted p < 0.05) were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and principal component and correlation analyses were used to characterize transcriptional changes under different treatments. Functional assays quantified interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion, intracellular triglyceride levels, and the lactate/pyruvate ratio.

Results: Metabolomics revealed medium-dependent remodeling of the exometabolome: BHI-derived supernatants were enriched in fatty acyls, glycerophospholipids, and pathways related to carbohydrate, energy, and lipid metabolism, whereas GAM-derived supernatants contained higher levels of sphingolipids and organic carbonic acids linked to purine and polyunsaturated fatty acid metabolism. Across four cell lines, DEGs induced by BHI-derived supernatants were mainly enriched in metabolic pathways, while GAM-derived supernatants more often engaged immune- and inflammation-related pathways. DEG overlap between cell types was limited, and KEGG enrichment and multivariate analyses supported cell type-specific transcriptional patterns. Functionally, GAM-derived supernatants significantly increased IL-6 and IL-8 secretion, whereas BHI-derived supernatants were more closely associated with changes in intracellular triglycerides and the lactate/pyruvate ratio in a cell-dependent manner (p < 0.05).

Conclusion: Metabolomic, transcriptomic, and functional data demonstrate that microbial culture conditions and host cell identity critically shape in vitro readouts of host–microbe interactions and should therefore be carefully considered when designing and interpreting microbiota-host interaction studies.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data Availability

The following information was supplied regarding data availability:

The datasets generated in this study are available in the NCBI Sequence Read Archive (SRA): PRJNA1226736 (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1226736) and PRJNA1226357 (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1226357).

The metabolomic data are available in the GSA-OMIX database: OMIX013095 (https://ngdc.cncb.ac.cn/omix/release/OMIX013095/).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 14 authors, 5 keywords, 9 MeSH terms, 5 funders, 62 references.

Cite

This paper

Liu, W., Zhang, T., Wang, Q., Li, Z., Bai, Y., Xiao, H., Wang, Y., Xiao, R., Tong, L., Li, Y., Qu, X., Zhao, X., Zhang, Z., & Sun, H. (2026). Transcriptomic and metabolomic profiling reveals media- and host-dependent responses to &lt;i&gt;Staphylococcus hominis&lt;/i&gt; in cell models. PeerJ, 14, e20899. https://doi.org/10.7717/peerj.20899

BibTeX

@article{liu2026transcriptomic,
author = {Liu, Wenxiu and Zhang, Tiansheng and Wang, Qian and Li, Zhunduo and Bai, Yanrui and Xiao, Han and Wang, Yan and Xiao, Ruihong and Tong, Liyu and Li, Yana and Qu, Xueli and Zhao, Xu and Zhang, Zhengchao and Sun, Hui},
title = {{Transcriptomic and metabolomic profiling reveals media- and host-dependent responses to \&lt;i\&gt;Staphylococcus hominis\&lt;/i\&gt; in cell models}},
journal = {PeerJ},
year = {2026},
month = mar,
volume = {14},
pages = {e20899},
publisher = {PeerJ, Inc},
issn = {2167-8359},
doi = {10.7717/peerj.20899},
url = {https://doi.org/10.7717/peerj.20899},
pmid = {41841123},
pmcid = {PMC12989153}
}

RIS

TY - JOUR
AU - Liu, Wenxiu
AU - Zhang, Tiansheng
AU - Wang, Qian
AU - Li, Zhunduo
AU - Bai, Yanrui
AU - Xiao, Han
AU - Wang, Yan
AU - Xiao, Ruihong
AU - Tong, Liyu
AU - Li, Yana
AU - Qu, Xueli
AU - Zhao, Xu
AU - Zhang, Zhengchao
AU - Sun, Hui
TI - Transcriptomic and metabolomic profiling reveals media- and host-dependent responses to &lt;i&gt;Staphylococcus hominis&lt;/i&gt; in cell models
T2 - PeerJ
J2 - PeerJ
PY - 2026
DA - 2026/03/12
VL - 14
SP - e20899
SN - 2167-8359
PB - PeerJ, Inc
DO - 10.7717/peerj.20899
UR - https://doi.org/10.7717/peerj.20899
LA - en
ER -

CSL-JSON

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