Probiotic therapy modulates the brain-gut-liver microbiota axis in a mouse model of traumatic brain injury

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1870; no. 8; p. 167483
• Main Authors: Amaral, Wellington Z., Kokroko, Natalie, Treangen, Todd J., Villapol, Sonia, Gomez-Pinilla, Fernando
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2024
• Subjects: Animals; Brain - metabolism; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - microbiology; Brain Injuries, Traumatic - therapy; Brain injury; Brain-Gut Axis; Disease Models, Animal; Gastrointestinal Microbiome - drug effects; Gut; Hippocampus - metabolism; Lipidomics; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Microbiota; Probiotics; Probiotics - administration & dosage; Probiotics - pharmacology; Probiotics - therapeutic use; Probiotics; Lipidomics; Microbiota; Brain injury; Gut
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167483

The interplay between gut microbiota and host health is crucial for maintaining the overall health of the body and brain, and it is even more crucial how changes in the bacterial profile can influence the aftermath of traumatic brain injury (TBI). We studied the effects of probiotic treatment after TBI to identify potential changes in hepatic lipid species relevant to brain function. Bioinformatic analysis of the gut microbiota indicated a significant increase in the Firmicutes/Bacteroidetes ratio in the probiotic-treated TBI group compared to sham and untreated TBI groups. Although strong correlations between gut bacteria and hepatic lipids were found in sham mice, TBI disrupted these links, and probiotic treatment did not fully restore them. Probiotic treatment influenced systemic glucose metabolism, suggesting altered metabolic regulation. Behavioral tests confirmed memory improvement in probiotic-treated TBI mice. While TBI reduced hippocampal mRNA expression of CaMKII and CREB, probiotics reversed these effects yet did not alter BDNF mRNA levels. Elevated pro-inflammatory markers TNF-α and IL1-β in TBI mice were not significantly affected by probiotic treatment, pointing to different mechanisms underlying the probiotic benefits. In summary, our study suggests that TBI induces dysbiosis, alters hepatic lipid profiles, and preemptive administration of Lactobacillus helveticus and Bifidobacterium longum probiotics can counter neuroplasticity deficits and memory impairment. Altogether, these findings highlight the potential of probiotics for attenuating TBI's detrimental cognitive and metabolic effects through gut microbiome modulation and hepatic lipidomic alteration, laying the groundwork for probiotics as a potential TBI therapy. •TBI changes the bacterial composition of the gut.•TBI affects hepatic lipid species and systemic glucose metabolism.•Probiotic administration influences bacterial composition.•Probiotic treatment restores select plasticity markers in the hippocampus associated with cognition.