<i>Lactiplantibacillus plantarum</i> WH021 Alleviates Lipopolysaccharide-Induced Neuroinflammation via Regulating the Intestinal Microenvironment and Protecting the Barrier Integrity

Neuroinflammation is one of the major pathological factors leading to neurodegenerative diseases (NDs). Currently, drug treatment is the main strategy for controlling NDs, but long-term drug use has many side effects. Studies have shown that probiotics can regulate neuroinflammation via the microbiota-gut-brain axis, thereby preventing and alleviating NDs. Our early studies screened several strains with antineuroinflammatory properties through the established microglia-zebrafish fast-screening model, and preliminary animal experiments demonstrated that <i>Lactiplantibacillus plantarum</i> WH021 has good antineuroinflammatory activity. Still, its specific effects and mechanisms need to be further explored. Therefore, this study aimed to investigate the effects of three doses of <i>L. plantarum</i> WH021 on behavioral disorders, brain and intestinal inflammation, and their possible mechanism in model mice with lipopolysaccharide (LPS)-induced neuroinflammation. The results showed that <i>L. plantarum</i> WH021 significantly improved the depression-like state caused by neuroinflammation, inhibited brain inflammation and neuronal damage, and enhanced synaptic function and blood-brain barrier integrity after 28 days of intervention in the high-dose group (10⁹ CFU/day). In addition, pathological damage and inflammation in the colon tissue were effectively alleviated, and the function of the intestinal barrier was improved. From the perspective of gut microbiota and serum metabolites, <i>L. plantarum</i> WH021 was also found to regulate intestinal homeostasis and increase serum metabolic levels of neuroactive components and neurotransmitter metabolites. Ultimately, 5-hydroxytryptaminergic synapses, GABAergic synapses, and the arachidonic acid pathway were identified as potential mechanisms exerting their ability to alleviate neuroinflammation. These findings may provide a possible strategy for preventing neuroinflammation-related diseases.