Hungatella hathewayi may mitigate post-mTBI cognitive impairment by boosting butyrate production, which alleviates intestinal inflammation, shifts microglia toward the protective M2 phenotype, reduces neuroinflammation, and supports neuroprotection.
Key Findings
Results
mTBI patients who developed cognitive impairment showed decreased Hungatella hathewayi, while those without cognitive impairment showed an increase in this bacterium.
This was a clinical observational finding in mTBI patients stratified by cognitive outcome
The divergent pattern of Hungatella hathewayi abundance distinguished cognitively impaired from non-impaired mTBI patients
The study was registered with the Chinese Clinical Trial Registry (ChiCTR2300072000) on May 31, 2023
Results
Microbiota transplantation with higher Hungatella hathewayi levels enriched beneficial short-chain fatty acid (SCFA)-producing bacteria and reduced harmful bacteria in mTBI rats.
The experiment was conducted using a microbiota transplantation model in mTBI rats
Higher Hungatella hathewayi levels were associated with enrichment of beneficial SCFA-producing bacterial populations
Harmful bacterial populations were concurrently reduced following transplantation
Results
Elevated Hungatella hathewayi improved spatial learning and memory performance in mTBI rats as measured by Morris water maze and novel object recognition tests.
Two behavioral paradigms were used: Morris water maze (spatial learning and memory) and novel object recognition test
Improved performance on both tests indicated enhanced cognitive function in animals with higher Hungatella hathewayi levels
This finding was demonstrated in the mTBI rat microbiota transplantation model
Results
Elevated Hungatella hathewayi 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.
Inflammatory markers assessed included TNF-α and IL-6 mRNA expression in both gut and brain tissue
M2 microglia polarization, representing the protective anti-inflammatory phenotype, was promoted in the peri-lesional cortex
These findings suggest Hungatella hathewayi exerts anti-neuroinflammatory effects through microglial phenotype modulation
Results
Metabolomics analysis identified increased fecal and serum butyrate levels associated with elevated Hungatella hathewayi following mTBI.
Both fecal and serum butyrate levels were elevated, indicating systemic availability of this SCFA
Butyrate is characterized in the paper as a SCFA with anti-neuroinflammatory properties
Metabolomics was used as the analytical approach to identify this metabolic change
Discussion
The proposed mechanism by which Hungatella hathewayi mitigates post-mTBI cognitive impairment involves a butyrate-mediated gut-brain axis pathway.
The proposed pathway involves boosting butyrate production, which alleviates intestinal inflammation
Butyrate is hypothesized to shift microglia toward the protective M2 phenotype and reduce neuroinflammation
The pathway ultimately supports neuroprotection and lowers cognitive impairment risk after mTBI
Du Q, Li Q, Ullah H, Wei Y, Liao G, Xiao X, et al.. (2026). Harnessing gut microbiota for brain health: protective role of Hungatella hathewayi for post-mTBI cognitive impairment.. NPJ biofilms and microbiomes. https://doi.org/10.1038/s41522-026-00922-y