Closed Head Injury Inulin Mouse Stool Samples Raw sequence reads

Mild traumatic brain injury has been shown to negatively alter bacterial diversity and composition within the gut, known as dysbiosis, in rodents and humans. These changes cause secondary consequences systemically through decreased bacterial metabolites such as short-chain fatty acids which play a role in inflammation and metabolism. The goal of the study was to identify if giving prebiotic inulin before closed head injury could mitigate gut dysbiosis, increase SCFAs, and improve recovery outcomes, including protecting cerebral blood flow and white matter integrity in young mice. We fed mice at 2 months of age with either inulin or control diet (with cellulous as fiber source) for two months before the CHI and continued for another 4 months. We analyzed gut microbiome composition and diversity, determined SCFAs levels, and measured CBF and WMI using MRI. We compared the results with Naive and Sham-injury mice at 24 hours, 1.5 months, and 3 months post-injury. We found that both CHI and Sham mice had gut dysbiosis after surgery but peaked at different time points. Inulin significantly reduced the abundance of pathobiont bacteria, such as E. Coli, Desulfovibrio spp and Pseudomonas aeruginosa, in Sham and CHI mice compared to mice fed with control diet. On the other hand, inulin increased SCFAs-producing bacteria, such as Bifidobacterium spp and Lactobacillus spp, increased levels of SCFAs, including butyrate and propionate, and significantly altered beta diversity as early as 24 hours post-injury, up to 3 months post-injury. The mitigation of dysbiosis is associated with protection of WMI in fimbria, internal and external capsule, and CBF in the right hippocampus of CHI mice, suggesting protection of memory and cognitive functions. The results indicate that inulin given prior to CHI could promote recovery outcome through gut microbiome modulation. As inulin, microbiome analysis and MRI are readily to be used in humans, the findings from the study may pave a way for a cost-effective, accessible intervention for those at risk of sustaining a head injury, such as military personnel or athletes in contact sports.