Allicin improves motor neuron survival in amyotrophic lateral sclerosis by reducing neuroinflammation and modulating gut microbiota.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons (MNs). Allicin, a defensive molecule in garlic with anti-inflammatory and gut microbiota-modulating properties, has shown therapeutic potential in animal models of various diseases including Alzheimer's disease (AD). However, its possible therapeutic role in ALS remains unclear. The purpose of this study is to investigate the therapeutic effect of allicin in ALS transgenic SOD1G93A mice. Starting at 60 days of age, SOD1G93A mice received oral gavage of allicin (10 mg/kg) on alternate days, while the control group received an equal volume of normal saline (NS) on the same schedule. Twelve mice per group were used for monitoring disease onset and survival. Nissl staining and choline acetyltransferase (ChAT) immunofluorescence were used to quantify MNs in the anterior horn. Microglial activation was analyzed by immunofluorescence staining for Iba1, ARG1, and CD86. The mRNA expression levels of IL-10, TGF-β, IL-1β, and TNF-α were examined using qPCR. Additionally, fecal samples were collected for 16S rDNA sequencing to evaluate changes in gut microbiota composition. We observed that allicin treatment failed to prolong the onset time and survival period of SOD1G93A mice, but it extended the disease duration. Nissl staining analysis revealed that allicin treatment delayed the loss of spinal MNs, a finding corroborated by ChAT immunofluorescence. Furthermore, allicin treatment significantly reduced neuroinflammation and improved gut microbiota. Taken together, although allicin may prolong disease duration in ALS, it did not improve overall survival or delay disease onset. Therefore, its potential disease-modifying effects require further validation.