BACKGROUND: Recent advances in gut-brain axis research have provided new insights into traumatic brain injury (TBI) treatment. Bifidobacterium longum subsp. infantis (B. infantis) has been demonstrated to reduce neuronal damage and alleviate cognitive symptoms in neurodegenerative diseases, yet its protective effect against TBI-induced cognitive impairment remains unclear.
OBJECTIVE: To investigate whether B. infantis can alleviate TBI-induced cognitive impairment in mice and explore its underlying mechanisms.
METHODS: Ninety SPF-grade C57BL/6 mice were randomly divided into sham-operated, TBI + saline, and TBI + B. infantis groups. A mild TBI model was established via controlled cortical impact (CCI). Mice in the TBI + B. infantis group received 150 μL of B. infantis suspension (10 CFU/mL) by gavage for 14 days before and 14 days after TBI; the other two groups received normal saline. Neurological function, pain sensitivity, and cognitive function were evaluated using behavioral tests. Histological, molecular biological, and biochemical analyses were performed to detect blood-brain barrier (BBB) integrity, hippocampal oxidative stress/inflammation, intestinal barrier function, and levels of trimethylamine N-oxide (TMAO) and methionine sulfoxide reductase A (MsrA). 9
RESULTS: B. infantis significantly improved TBI-induced neurological deficits, hyperalgesia, and cognitive impairment. Mechanistically, it directly protected the central nervous system by maintaining BBB integrity (promoting the expression of tight junction proteins occludin and ZO-1) and inhibiting hippocampal oxidative stress (reducing ROS levels) and inflammation (suppressing IL-1β, IL-6, and TNF-α expression). Indirectly, it repaired intestinal barrier integrity (reducing serum D-lactate levels and upregulating occludin expression), inhibited intestinal inflammation (suppressing IL-6 expression), regulated TMAO metabolism (reducing serum and cerebrospinal fluid TMAO levels), and restored hippocampal MsrA expression.
CONCLUSIONS: B. infantis exerts a protective effect against TBI through direct protection of the central nervous system and indirect regulation of intestinal homeostasis, providing a new candidate for adjuvant treatment of TBI and advancing gut-brain axis research in neurological diseases.
