Weizmannia coagulans BC99 Improve Cognitive Impairment Induced by Chronic Sleep Deprivation via Inhibiting the Brain and Intestine’s NLRP3 Inflammasome

<i>Weizmannia coagulans</i> BC99, a Gram-positive, spore-forming, lactic acid-producing bacterium is renowned for its resilience and health-promoting properties, <i>W. coagulans</i> BC99 survives harsh environments, including high temperatures and gastric acidity, enabling effective delivery to the intestines. The consequences of chronic sleep deprivation (SD) include memory deficits and gastrointestinal dysfunction. In this study, a chronic sleep deprivation cognitive impairment model was established by using a sleep deprivation instrument and <i>W. coagulans</i> BC99 was given by gavage for 4 weeks to explore the mechanism by which BC99 improves cognitive impairment in sleep-deprived mice. BC99 improved cognitive abnormalities in novel object recognition tests induced by chronic sleep deprivation and showed behavior related to spatial memory in the Morris water maze test. <i>W. coagulans</i> BC99 reduced the heart mass index of sleep-deprived mice, increased the sleep-related neurotransmitters 5-HT and DA, decreased corticosterone and norepinephrine, and increased alpha diversity and community similarity. It reduced the abundance of harmful bacteria such as <i>Olsenella</i>, increased the abundance of beneficial bacteria such as <i>Lactobacillus</i> and <i>Bifidobacterium</i>, and promoted the production of short-chain fatty acids (SCFAs). <i>W. coagulans</i> BC99 also inhibits LPS translocation and the elevation of peripheral inflammatory factors by maintaining the integrity of the intestinal barrier and inhibiting the expression of the <i>NLRP3</i> signaling pathway in the jejunum, thereby inhibiting the <i>NLRP3</i> inflammasome in the brain of mice and reducing inflammatory factors in the brain, providing a favorable environment for the recovery of cognitive function. The present study confirmed that <i>W. coagulans</i> BC99 ameliorated cognitive impairment in chronic sleep-deprived mice by improving gut microbiota, especially by promoting SCFAs production and inhibiting the <i>NLRP3</i> signaling pathway in the jejunum and brain. These findings may help guide the treatment of insomnia or other sleep disorders through dietary strategies.