Pre-traumatic antibiotic-induced microbial depletion reduces neuroinflammation in acute murine traumatic brain injury

The connection between dysbiosis of the gut microbiome and diseases and injuries of the brain has attracted considerable interest in recent years. Interestingly, antibiotic-induced microbial dysbiosis has been implicated in the pathogenesis of traumatic brain injury (TBI), while early administration of antibiotics associates with improved survival in TBI patients. In animal models of TBI, short- or long-term administration of antibiotics, both peri- or post-operatively, were shown to induce gut microbiome dysbiosis but also anti-inflammatory and neuroprotective effects. However, the acute consequences of microbial dysbiosis on TBI pathogenesis after discontinuation of antibiotic treatment are elusive. In this study, we tested whether pre-traumatic antibiotic-induced microbial depletion by vancomycin, amoxicillin, and clavulanic acid affects pathogenesis during the acute phase of TBI in adult male C57BL/6 mice. Pre-traumatic microbiome depletion did not affect neurological deficits over 72 h post injury (hpi) and brain histopathology, including numbers of activated astrocytes and microglia, at 72 hpi. However, astrocytes and microglia were smaller after pre-traumatic microbiome depletion compared to vehicle treatment at 72 hpi, indicating less inflammatory activation. Accordingly, TBI-induced gene expression of the inflammation markers Interleukin-1β, complement component C3, translocator protein TSPO and the major histocompatibility complex MHC2 was attenuated in microbiome-depleted mice along with reduced Immunoglobulin G extravasation as a proxy of blood-brain barrier (BBB) impairment. These results suggest that the gut microbiome contributes to early neuroinflammatory responses to TBI but does not have a significant impact on brain histopathology and neurological deficits. This article is part of the Special Issue on “Microbiome & the Brain: Mechanisms & Maladies”. •Pre-traumatic antibiosis to achieve microbiome dysbiosis during acute murine TBI.•Microbiome dysbiosis contributes to neuroinflammatory responses in acute murine TBI.•No significant impact on brain histopathology and neurological deficits.