TBI is regarded as a chronic disease that may affect multiple functional domains. Studies have shown that brain function impairment caused by TBI may gradually worsen over time, and many TBI patients still remain in a state of moderate to severe disability five years after injury (Dams-O'Connor et al., 2023; Li et al., 2025). TBI can induce a variety of neurological complications, ranging from simple headache in mild cases to permanent memory impairment and cognitive dysfunction in severe cases. Cognitive impairment is a common and important sequela that affects patients' daily life and social functions, mainly manifested as memory impairment, inattention, executive dysfunction, and slowed information processing speed. In brain injury, the cerebral cortex and hippocampus are the two brain structures most susceptible to impacts (Tong et al., 2002). Since hippocampal neurons play a key role in learning and memory functions, their damage may lead to an increased risk of cognitive dysfunction (Ozdemir et al., 2005).

Despite advances in healthcare and research, gaps remain in gaining a comprehensive understanding of the disease's burden, particularly when it comes to enhancing treatments to achieve better outcomes. In fact, the U.S. Food and Drug Administration (FDA) has not yet approved any definitive therapy for treating secondary brain injury following TBI that can modify the disease course. Given the remarkable research progress achieved in the field of the gut-brain axis, exploring gut microbiota-targeted interventions has become a promising direction for TBI treatment.

Bifidobacteria are key members of the human microbiome with crucial roles in gastrointestinal health throughout lifespan (Arboleya et al., 2016). Among them, B. infantis exhibits prominent probiotic properties, including modulating immune responses, suppressing inflammation, enhancing intestinal barrier function, and promoting metabolite production (Sela and Mills, 2010; Underwood et al., 2015). Multiple studies have demonstrated that B. infantis—alone or in combination with other probiotics—can reduce neuronal damage and alleviate cognitive-related symptoms in neurodegenerative diseases (Reiriz et al., 2025).

Despite the well-reported benefits of B. infantis in supporting gut health, modulating immunity, and alleviating neuronal damage in neurodegenerative diseases, its potential role in mitigating TBI-induced cognitive impairment remains unclear. Therefore, the present study aims to investigate whether B. infantis can alleviate TBI-induced cognitive impairment in mice and clarify its potential protective mechanisms.