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Probiotics Improve Cognitive Impairment by Decreasing Bacteria-Related Pattern Recognition Receptor-Mediated
Xue-Qin Yang1, Yang Zhao1, Li Xue2
1Department of Pharmacy, Guangyuan Central Hospital, Affiliated Hospital of North Sichuan Medical College, 628000 Guangyuan, Sichuan, China.
Introduction:
Some studies have found that probiotics can improve cognitive impairment in Alzheimer's disease, although the specific molecular mechanism by which this occurs has not been reported. Our previous research found that probiotics inhibited bacteria-related Toll-like receptor 4- and retinoic-acid-inducible gene-I-mediated nuclear factor-κB signaling pathways to improve cognitive impairment. However, it is unclear whether probiotics have similar effects on other pattern recognition receptors that respond to bacteria.
Methods:
Nine-month-old senescence-accelerated mouse prone 8 (SAMP8) mice received ProBiotic-4 (a mixture of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus casei, and Bifidobacterium lactis) orally for 12 weeks. The effects on other bacteria-related pattern recognition receptors were then investigated.
Results:
ProBiotic-4-treated SAMP8 mice showed improvement in memory deficits, synaptic and cerebral neuronal injuries, and microglial activation. ProBiotic-4 also markedly increased the expression of intestinal tight junction proteins (i.e., claudin-1, occludin, and zonula occluden-1), decreased the expression of interleukin-1β at both the mRNA and protein levels, and reduced the expression of caspase-11, cleaved caspase-1, and α-kinase 1 (ALPK1) in the intestine and brain.
Conclusions:
These findings suggest that probiotics may have therapeutic potential for the treatment of inflammation in the gut-brain axis and for cognitive impairment. The mechanism of action of probiotics appears to be related to inhibition of the caspase-11/caspase-1 pathway and reduction of ALPK1 expression.
Insights
Probiotics improved cognitive impairment in mice by reducing gut-brain axis inflammation. This therapeutic potential involves inhibiting the caspase-11/caspase-1 pathway and decreasing alpha-kinase 1 expression.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Emerging research suggests probiotics may alleviate cognitive impairment in Alzheimer's disease.
- Previous studies linked probiotics to improved cognition via Toll-like receptor 4 and retinoic-acid-inducible gene-I pathways.
- The impact of probiotics on other bacterial pattern recognition receptors remains largely unexplored.
Purpose of the Study:
- To investigate the effects of probiotics on cognitive impairment in senescence-accelerated mice.
- To elucidate the molecular mechanisms underlying probiotic-mediated improvements in cognitive function.
- To explore probiotic interactions with various bacteria-related pattern recognition receptors.
Main Methods:
- Senescence-accelerated mouse prone 8 (SAMP8) mice were administered ProBiotic-4 (a mix of four bacterial strains) orally for 12 weeks.
- Cognitive function, synaptic integrity, neuronal injury, and microglial activation were assessed.
- Expression levels of intestinal tight junction proteins, inflammatory cytokines (interleukin-1β), and key signaling molecules (caspase-11, caspase-1, and α-kinase 1) were analyzed.
Main Results:
- ProBiotic-4 treatment significantly improved memory deficits and reduced neuronal damage and microglial activation in SAMP8 mice.
- Probiotic administration enhanced intestinal barrier function by increasing tight junction protein expression.
- Key inflammatory markers, including interleukin-1β, caspase-11, cleaved caspase-1, and α-kinase 1 (ALPK1), were significantly downregulated in both the intestine and brain.
Conclusions:
- Probiotics demonstrate therapeutic potential for managing gut-brain axis inflammation and cognitive impairment.
- The observed benefits are associated with the inhibition of the caspase-11/caspase-1 signaling pathway.
- Probiotic-induced reduction in ALPK1 expression is a key mechanism contributing to cognitive improvement.
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