Probiotics Improve Cognitive Impairment by Decreasing Bacteria-Related Pattern Recognition Receptor-Mediated Inflammation in the Gut-Brain Axis of Mice.

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. 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. 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. 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.

Yang XQ ，Zhao Y ，Xue L ，Wang HS ，Zeng J ，Du JR ，Xu Z ... -  《Journal of Integrative Neuroscience》

Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice.

ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus acidophilus. This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor-α at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-κB (NF-κB) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of γ-H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.

Yang X ，Yu D ，Xue L ，Li H ，Du J ... -  《-》

Multi-strain probiotics ameliorate Alzheimer's-like cognitive impairment and pathological changes through the AKT/GSK-3β pathway in senescence-accelerated mouse prone 8 mice.

Alzheimer's disease (AD), the most prevalent type of dementia, still lacks disease-modifying treatment strategies. Recent evidence indicates that maintaining gut microbiota homeostasis plays a crucial role in AD. Targeted regulation of gut microbiota, including probiotics, is anticipated to emerge as a potential approach for AD treatment. However, the efficacy and mechanism of multi-strain probiotics treatment in AD remain unclear. In this study, 6-month-old senescence-accelerated-mouse-prone 8 (SAMP8) and senescence-accelerated-mouse-resistant 1 (SAMR1) were utilized. The SAMP8 mice were treated with probiotic-2 (P2, a probiotic mixture of Bifidobacterium lactis and Lactobacillus rhamnosus) and probiotic-3 (P3, a probiotic mixture of Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus rhamnosus) (1 × 109 colony-forming units) once daily for 8 weeks. Morris water maze (MWM) and novel object recognition (NOR) tests were employed to assess the memory ability. 16S sequencing was applied to determine the composition of gut microbiota, along with detecting serum short-chain fatty acids (SCFAs) concentrations. Neural injury, Aβ and Tau pathology, and neuroinflammation level were assessed through western blot and immunofluorescence. Finally, potential molecular mechanisms was explored through transcriptomic analysis and western blotting. The MWM and NOR test results indicated a significant improvement in the cognitive level of SAMP8 mice treated with P2 and P3 probiotics compared to the SAMP8 control group. Fecal 16S sequencing revealed an evident difference in the α diversity index between SAMP8 and SAMR1 mice, while the α diversity of SAMP8 mice remained unchanged after P2 and P3 treatment. At the genus level, the relative abundance of ten bacteria differed significantly among the four groups. Multi-strain probiotics treatment could modulate serum SCFAs (valeric acid, isovaleric acid, and hexanoic acid) concentration. Neuropathological results demonstrated a substantial decrease in neural injury, Aβ and Tau pathology and neuroinflammation in the brain of SAMP8 mice treated with P3 and P2. Transcriptomic analysis identified the chemokine signaling pathway as the most significantly enriched signaling pathway between SAMP8 and SAMR1 mice. Western blot test indicated a significant change in the phosphorylation level of downstream AKT/GSK-3β between the SAMP8 and SAMR1 groups, which could be reversed through P2 and P3 treatment. Multi-strain probiotics treatment can ameliorate cognitive impairment and pathological change in SAMP8 mice, including neural damage, Aβ and Tau pathology, and neuroinflammation. This effect is associated with the regulation of the phosphorylation of the AKT/GSK-3β pathway.

Xiao-Hang Q ，Si-Yue C ，Hui-Dong T 《-》

Citation: Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with Colitis in Mice.

Ma XY ，Son YH ，Yoo JW ，Joo MK ，Kim DH ... -  《Nutrients》

Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer's disease.

Cui B ，Su D ，Li W ，She X ，Zhang M ，Wang R ，Zhai Q ... -  《Journal of Neuroinflammation》