Temporal shifts to the gut microbiome associated with cognitive dysfunction following high-fat diet consumption in a juvenile model of traumatic brain injury.

The gut-brain axis interconnects the central nervous system (CNS) and the commensal bacteria of the gastrointestinal tract. The composition of the diet consumed by the host influences the richness of the microbial populations. Traumatic brain injury (TBI) produces profound neurocognitive damage, but it is unknown how diet influences the microbiome following TBI. The present work investigates the impact of a chow diet versus a 60% fat diet (HFD) on fecal microbiome populations in juvenile rats following TBI. Twenty-day-old male rats were placed on one of two diets for 9 days before sustaining either a Sham or TBI via the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). Fecal samples were collected at both 1- and 9-days postinjury. Animals were cognitively assessed in the novel object recognition tests at 8 days postinjury. Fecal microbiota DNA was isolated and sequenced. Twenty days of HFD feeding did not alter body weight, but fat mass was elevated in HFD compared with Chow rats. TBI animals had a greater percentage of entries to the novel object quadrant than Sham counterparts, P < 0.05. The Firmicutes/Bacteroidetes ratio was significantly higher in TBI than in the Sham, P < 0.05. Microbiota of the Firmicutes lineage exhibited perturbations by both injury and diet that were sustained at both time points. Linear regression analyses were performed to associate bacteria with metabolic and neurocognitive endpoints. For example, counts of Lachnospiraceae were negatively associated with percent entries into the novel object quadrant. Taken together, these data suggest that both diet and injury produce robust shifts in microbiota, which may have long-term implications for chronic health.NEW & NOTEWORTHY Traumatic brain injury (TBI) produces memory and learning difficulties. Diet profoundly influences the populations of gut microbiota. Following traumatic brain injury in a pediatric model consuming either a healthy or high-fat diet (HFD), significant shifts in bacterial populations occur, of which, some are associated with diet, whereas others are associated with neurocognitive performance. More work is needed to determine whether these microbes can therapeutically improve learning following trauma to the brain.

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury.

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

Early depletion of gut microbiota shape oligodendrocyte response after traumatic brain injury.

White matter injury (WMI) is thought to be a major contributor to long-term cognitive dysfunctions after traumatic brain injury (TBI). This damage occurs partly due to apoptotic death of oligodendrocyte lineage cells (OLCs) after the injury, triggered directly by the trauma or in response to degenerating axons. Recent research suggests that the gut microbiota modulates the inflammatory response through the regulation of peripheral immune cell infiltration after TBI. Additionally, T-cells directly impact OLCs differentiation and proliferation. Therefore, we hypothesized that the gut microbiota plays a critical role in regulating the OLC response to WMI influencing T-cells differentiation and activation. Gut microbial depletion early after TBI chronically reduced re-myelination, acutely decreased OLCs proliferation, and was associated with increased myelin debris accumulation. Surprisingly, the absence of T-cells in gut microbiota depleted mice restored OLC proliferation and remyelination after TBI. OLCs co-cultured with T-cells derived from gut microbiota depleted mice resulted in impaired proliferation and increased expression of MHC-II compared with T cells from control-injured mice. Furthermore, MHC-II expression in OLCs appears to be linked to impaired proliferation under gut microbiota depletion and TBI conditions. Collectively our data indicates that depletion of the gut microbiota after TBI impaired remyelination, reduced OLCs proliferation with concomitantly increased OLC MHCII expression, and required the presence of T cells. This data suggests that T cells are an important mechanistic link by which the gut microbiota modulate the oligodendrocyte response and white matter recovery after TBI.

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury.

Objective: The current study sought to clarify the role of lysozyme-regulated gut microbiota and explored the potential therapeutic effects of lysozyme on ileum injury induced by severe traumatic brain injury (sTBI) and bacterial pneumonia in vivo and in vitro experiments. Methods: Male 6-8-week-old specific pathogen-free (SPF) C57BL/6 mice were randomly divided into Normal group (N), Sham group (S), sTBI group (T), sTBI + or Lysozyme-treated group (L), Normal + Lysozyme group (NL) and Sham group + Lysozyme group (SL). At the day 7 after establishment of the model, mice were anesthetized and the samples were collected. The microbiota in lungs and fresh contents of the ileocecum were analyzed. Lungs and distal ileum were used to detect the degree of injury. The number of Paneth cells and the expression level of lysozyme were assessed. The bacterial translocation was determined. Intestinal organoids culture and co-coculture system was used to test whether lysozyme remodels the intestinal barrier through the gut microbiota. Results: After oral administration of lysozyme, the intestinal microbiota is rebalanced, the composition of lung microbiota is restored, and translocation of intestinal bacteria is mitigated. Lysozyme administration reinstates lysozyme expression in Paneth cells, thereby reducing intestinal permeability, pathological score, apoptosis rate, and inflammation levels. The gut microbiota, including Oscillospira, Ruminococcus, Alistipes, Butyricicoccus, and Lactobacillus, play a crucial role in regulating and improving intestinal barrier damage and modulating Paneth cells in lysozyme-treated mice. A co-culture system comprising intestinal organoids and brain-derived proteins (BP), which demonstrated that the BP effectively downregulated the expression of lysozyme in intestinal organoids. However, supplementation of lysozyme to this co-culture system failed to restore its expression in intestinal organoids. Conclusion: The present study unveiled a virtuous cycle whereby oral administration of lysozyme restores Paneth cell's function, mitigates intestinal injury and bacterial translocation through the remodeling of gut microbiota.

Metagenomic sequencing of the skin microbiota of the scalp predicting the risk of surgical site infections following surgery of traumatic brain injury in sub-Saharan Africa.

BACKGROUND: Surgical site infections (SSI) are a significant concern following traumatic brain injury (TBI) surgery and often stem from the skin's microbiota near the surgical site, allowing bacteria to penetrate deeper layers and potentially causing severe infections in the cranial cavity. This study investigated the relationship between scalp skin microbiota composition and the risk of SSI after TBI surgery in sub-Saharan Africa (SSA). METHODS: This was a prospective cohort study, enrolling patients scheduled for TBI surgery. Sterile skin swabs were taken from the surrounding normal skin of the head and stored for analysis at -80°Celcius. Patients were monitored postoperatively for up to three months to detect any occurrences of SSI. 16S rRNA sequencing was used to analyze the skin microbiota composition, identifying different taxonomic microorganisms at the genus level. The analysis compared two groups: those who developed SSI and those who did not. RESULTS: A total of 57 patients were included, mostly male (89.5%) with a mean age of 26.5 years, predominantly from urban areas in Uganda and victims of assault. Graphical visualization and metagenomic metrics analysis revealed differences in composition, richness, and evenness of skin microbiota within samples (α) or within the community (ß), and showed specific taxa (phylum and genera) associated with either the group of SSI or the No SSI. CONCLUSIONS: Metagenomic sequencing analysis uncovered several baseline findings and trends regarding the skin microbiome's relationship with SSI risk. There is an association between scalp microbiota composition (abundancy and diversity) and SSI occurrence following TBI surgery in SSA. We hypothesize under reserve that the scalp microbiota dysbiosis could potentially be an independent predictor of the occurrence of SSI; we advocate for further studies with larger cohorts.