Partially hydrolyzed guar gum alleviates neurological deficits and gastrointestinal dysfunction in mice with...

Traumatic brain injury (TBI)-associated neuroinflammation and neurotoxicity can induce gastrointestinal dysfunction through the brain-gut axis. Partially hydrolyzed guar gum (PHGG) was demonstrated to exert beneficial health effects by altering gut microbiota and short-chain fatty acids (SCFAs) production. Our study aimed to explore the effects of PHGG on gastrointestinal dysfunction in TBI mouse models. Controlled cortical impact (CCI)-induced TBI mouse models were administrated with PHGG (600 mg/kg/d) for 21 consecutive days. Behavioral tests (modified neurological severity score and beam walk test) and Y‑maze assay were performed to evaluate neurological functions and cognitive impairment. Enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and western blotting examined the levels of inflammatory cytokines, intestinal mucosal damage markers, intestinal tight junction proteins, and NLRP3 inflammasome-related molecules in the serum, cerebral cortex, and colon tissues. The histological changes in the cerebral cortex and colon tissues were observed through hematoxylin and eosin and Nissl staining. Liquid chromatography/mass spectrometry analyzed SCFA amounts in the cecum contents and bile acid levels in the serum. PHGG administration alleviated neurological deficits and cognitive perturbations, reduced neuroinflammation, and attenuated cortical tissue damage and neuron loss in TBI mice. PHGG ameliorated intestinal barrier impairment, upregulated intestinal production of SCFAs, and elevated serum bile acid levels in TBI mice. Besides, PHGG treatment repressed NLRP3 inflammasome activation in TBI mice. Overexpressing NLRP3 reversed the beneficial effects of PHGG against TBI in mice. PHGG ameliorates neuroinflammation and gastrointestinal dysfunction in TBI murine models by inhibiting NLRP3 inflammasome activation.