Abstract
Cognitive impairment (CI) following mild traumatic brain injury (mTBI) poses a clinical challenge, with emerging evidence implicating gut microbiota. This study found that mTBI patients who developed CI exhibited decreased Hungatella hathewayi, while those without CI showed an increase. Microbiota transplantation in mTBI rats revealed that higher Hungatella hathewayi levels enriched beneficial, short-chain fatty acid (SCFA) -producing bacteria and reduced harmful ones. Elevated Hungatella hathewayi improved performance in the Morris water maze and novel object recognition tests, indicating enhanced spatial learning and memory. It also reduced gut and brain inflammation, shown by lower TNF-α and IL-6 mRNA expression, and promoted M2 microglia polarization in the peri-lesional cortex. Metabolomics identified increased fecal and serum butyrate, a SCFA with anti-neuroinflammatory properties. Thus, Hungatella hathewayi may mitigate Post-mTBI CI by boosting butyrate production, which alleviates intestinal inflammation, shifts microglia toward the protective M2 phenotype, reduces neuroinflammation, and supports neuroprotection, ultimately lowering CI risk after mTBI. This study was registered with the Chinese Clinical Trial Registry (ChiCTR) on May 31, 2023 (Registration number: ChiCTR2300072000, URL: https://www.chictr.org.cn/showproj.html?proj=197867).
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Data availability
The data supporting this study cannot be made publicly available due to ethicaland privacy concerns, as they contain sensitive information that could compromise the confidentiality of human subjects. Access to the data is restricted to protect participant anonymity and comply with institutional and legal requirements. Requests for limited, anonymized data may be considered on a case-by-case basis, subject to approval by the relevant ethics committee.
Code availability
The underlying code for this study is not publicly available but may be made available to qualified researchers on reasonable request from the corresponding author.
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Acknowledgements
We would like to acknowledge the National Natural Science Foundation of China and the Sichuan Provincial Department of Science and Technology for their financial support of this research. (Grant number: U22A20334, 2024NSFSC0592, and 2025ZNSFSC1691).
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D.Q., L.Q., and L.K. conducted the entire experiment and wrote the manuscript; L.Q. and L.K. are responsible for the paper; W.Y., L.G., X.X., and Y.J. prepared Figs. 1–7 and Tables 1–3; H.U. polished the language of the paper. All authors have read and approved the final version of the manuscript.
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Du, Q., Li, Q., Ullah, H. et al. Harnessing gut microbiota for brain health: protective role of Hungatella hathewayi for post-mTBI cognitive impairment. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00922-y
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DOI: https://doi.org/10.1038/s41522-026-00922-y
