Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury

Abstract

Key roles of the gut−brain axis in brain injury development have been suggested in various mouse models; however, little is known about its functional significance in human mild traumatic brain injury (TBI). Here, we deciphered this axis by profiling the gut microbiota in 98 acute mild TBI patients and 62 matched controls, and subgroup of them also measured circulating mediators and applied neuroimaging. Mild TBI patients had increased α−diversity and different overall microbial compositions compared with controls. 25−microbial genus classifiers distinguished patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.889, while adding serum mediators and neuroimaging features further improved performance even in a small sample size (AUC = 0.969). Numerous correlations existed between gut bacteria, aberrant cortical thickness and cerebrovascular injury. Co−occurrence network analysis revealed two unique gut−brain axes in patients: 1) altered intestinal Lachnospiraceae_NK4A136_group and Eubacterium_ruminantium_group-increased serum GDNF−subcallosal hypertrophy and cerebrovascular injury; 2) decreased intestinal Eubacterium_xylanophilum_group−upregulated IL−6−thinned anterior insula. Our findings provided a new integrated mechanistic understanding and diagnostic model of mild TBI.

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase

“…Reduced cerebral blood flow (CBF) [ 5 , 6 ] and impaired white matter integrity (WMI) [ 7 ] are typical phenotypes of mTBI. Recent studies further show that mTBI significantly alters the balance of microbial communities in the gut of rodents and humans, known as gut dysbiosis [ 8 – 10 ].The effects of neurotrauma radiate to the intestine and alter the composition and diversity of the gut microbiome. This results in reduced levels of putatively beneficial bacteria which in turn leads to the reduction of short-chain fatty acids (SCFAs), bacterial metabolites that play a key role in modulating metabolism, vascular response, and inflammation system-wide [ 11 , 12 ].…”

“…This results in reduced levels of putatively beneficial bacteria which in turn leads to the reduction of short-chain fatty acids (SCFAs), bacterial metabolites that play a key role in modulating metabolism, vascular response, and inflammation system-wide [ 11 , 12 ]. Dysbiosis has been shown to occur in the acute phase as early as one day post injury in rodent models [ 9 ] and humans [ 10 ]. Elucidating that TBI induces dysbiosis pinpoints the gut microbiome as a potential target to protect against the secondary injury cascade known to follow TBI [ 13 ].…”

Dysbiosis of Gut Microbiome Is Associated With Rupture of Cerebral Aneurysms

“…Therefore, we compared the gut microbiome immediately following the rupture with that of long-term stable UIAs in this study. However, brain damage itself, such as ischemic stroke and even mild traumatic brain injury, is already widely known to affect the gut microbiome, 21,22 which would be true in SAH. This is because the communication between gut and brain is regulated by mediators such as immune modulatory metabolites, gut peptides, neurotransmitters, and cytokines.…”