Gamma -aminobutyric acid ameliorates neurological impairments in type 1 diabetes mellitus mice by regulating the "gut flora-LPS-TLR4-NF-ΚB" signalling Axis.

This study examined the potential impact of gamma-aminobutyric acid (GABA) supplementation on the progression of type 1 diabetes mellitus (T1DM) through alterations in gut flora and its associated effects on neurological functions. A T1DM mouse model was created using streptozotocin. The study employed flow cytometry to analyze colonic Th17/Treg cells, 16 S rRNA sequencing to analyze microbiota, and western blot to evaluate colonic proteins. Neurological impairments were assessed through various tests. GABA intervention improved blood glucose levels, body weight, and oral glucose tolerance test (OGTT) results in T1DM mice. It also reduced serum LPS, IL-6, and TNF-α levels. GABA mitigated changes in the expressions of Th17 and Treg cells in T1DM mice. GABA-treated mice had more intestinal flora than T1DM mice. TLR4, MyD88, and NF-κB levels decreased with GABA, while Occludin and ZO-1 expressions increased. GABA improved neurological assessments, reduced neuronal damage and apoptosis, and lowered hippocampal LPS, IL-6, and TNF-α levels in T1DM mice. These findings indicated that GABA can manage T1DM by ameliorating hyperglycemia, reducing inflammation, regulating intestinal microbiota, modulating colonic protein expression, and alleviating neurological impairment.