Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.
Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.
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DOI：
10.33696/immunology.4.132
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Lin, Ai-Ling
中科院分区：
文献类型：
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作者：
Yanckello, Lucille M;Fanelli, Brian;McCulloch, Scott;Xing, Xin;Sun, McKenna;Hammond, Tyler C;Colwell, Rita;Gu, Zezong;Ericsson, Aaron C;Chang, Ya-Hsuan;Bachstetter, Adam D;Lin, Ai-Ling
轻度创伤性脑损伤（mTBI）已被证明会严重改变肠道微生物群的多样性和组成，即所谓的生态失调，这可能进一步加剧人类和啮齿动物大脑中的代谢和血管变化。然而，目前尚不清楚mTBI如何影响慢性恢复期（损伤后一周）的肠道微生物群。目前还不清楚是否可以通过减轻生态失调来改善损伤恢复。这项研究的目的是填补知识空白。首先，我们的目标是了解mTBI如何通过慢性恢复期（损伤后3个月）改变肠道微生物群。此外，由于肠道微生物组可以通过饮食调节，我们还研究了益生元菊粉（一种促进有益菌和代谢物生长的发酵纤维）在闭合性脑损伤（CHI）后3个月给予是否会减轻生态失调，改善全身代谢，并保护脑结构和血管完整性。我们发现，雄性小鼠在4月龄时给予CHI可引起肠道生态失调，这种失调在损伤后1.5个月达到顶峰，脑血流量（CBF）减少，脑白质完整性改变。有趣的是，我们还发现Sham小鼠有短暂的生态失调，在损伤后24小时达到峰值，然后恢复正常。饲喂菊粉8周后，与CHI对照组和Sham组相比，CHI小鼠的有益/抗炎细菌丰度增加，致病性细菌丰度降低，短链脂肪酸水平增加，海马和左丘脑的CBF恢复。通过机器学习，我们进一步确定了区分Sham和CHI小鼠的顶级细菌种类。我们的结果表明，CHI和Sham小鼠之间存在损伤依赖性和时间依赖性的生态失调；菊粉能有效减轻CHI小鼠的生态失调，促进脑损伤恢复。由于目前尚无有效的mTBI治疗方法，因此该研究可能对未来开发治疗方法或预防性干预措施具有深远的意义。
Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.