Short-Chain Fatty Acid Supplementation After Traumatic Brain Injury Attenuates Neurologic Injury Via the...

Area of Science:

• Neuroscience
• Microbiome research
• Traumatic Brain Injury (TBI) research

Background:

• Traumatic brain injury (TBI) is a significant public health issue with limited treatment options.
• Previous research demonstrated fecal microbiome transplantation (FMT) efficacy in mitigating TBI effects in mice.
• Gut microbiome dysbiosis is increasingly recognized as a factor in TBI pathology.

Purpose of the Study:

• To investigate the therapeutic potential of Short Chain Fatty Acids (SCFAs) supplementation in attenuating neurologic injury following TBI in a mouse model.
• To determine if SCFA administration could reverse TBI-induced gut microbiome alterations and improve neurological outcomes.
• To explore the impact of SCFAs on neuroinflammation and brain structural integrity post-TBI.

Main Methods:

• Mice with controlled cortical impact TBI were treated with SCFAs (acetate, butyrate, propionate) or a saline vehicle.
• Gut microbial composition was analyzed using 16S rRNA gene sequencing.
• Neurocognitive function was assessed via open-field and zero-maze tests.
• Brain structural changes (ventricular volume, white matter connectivity) were evaluated using MRI.
• Microglial transcriptional responses were profiled using single-cell RNA sequencing (scRNAseq).

Main Results:

• SCFA supplementation preserved gut microbial diversity and reduced TBI-induced bacterial loss.
• SCFAs attenuated ventricular volume expansion and preserved white matter connectivity post-TBI.
• TBI mice supplemented with SCFAs exhibited improved anxiety-like behaviors and cognitive function.
• Microglial analysis revealed a shift towards a neuroprotective transcriptional profile, with increased heat shock proteins and decreased neurodegeneration markers.

Conclusions:

• Post-TBI SCFA supplementation effectively attenuated neurological deficits, reduced brain volume loss, and preserved white matter integrity in mice.
• The neuroprotective effects may stem from direct SCFA action, restoration of butyrate-producing bacteria, and modulation of microglial inflammatory responses.
• Dietary interventions targeting the gut microbiome, such as SCFA supplementation, represent a promising therapeutic strategy for TBI management.