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. 2025 Mar 14;14(6):989.
doi: 10.3390/foods14060989.

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

Qiaoqiao Sun  1 , Jiajia Fan  1 , Lina Zhao  1   2 , Zhen Qu  1 , Yao Dong  3 , Ying Wu  1   2 , Shaobin Gu  1   2   3
Affiliations

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

Qiaoqiao Sun et al. Foods. .

Abstract

Weizmannia coagulans BC99, a Gram-positive, spore-forming, lactic acid-producing bacterium is renowned for its resilience and health-promoting properties, W. coagulans 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 W. coagulans 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. W. coagulans 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 Olsenella, increased the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, and promoted the production of short-chain fatty acids (SCFAs). W. coagulans 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 NLRP3 signaling pathway in the jejunum, thereby inhibiting the NLRP3 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 W. coagulans BC99 ameliorated cognitive impairment in chronic sleep-deprived mice by improving gut microbiota, especially by promoting SCFAs production and inhibiting the NLRP3 signaling pathway in the jejunum and brain. These findings may help guide the treatment of insomnia or other sleep disorders through dietary strategies.

Keywords: NLRP3 signaling pathway; W. coagulans; chronic sleep disorder; cognitive deficits; inflammation.

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Conflict of interest statement

The authors Yao Dong were employed by the company of Wecare Probiotics Co., Ltd., Suzhou, China. The three authors participated in the sample testing and formal analysis in the study. The role of the company was as a research participating unit. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Experiment timeline.
Figure 2
Figure 2
Effects of BC99 on behavioral and physiological indices of chronic sleep deprivation mice (n = 6). (A) Discrimination index. (B) Recognition index. (C) Latency to reach the platform. (D) Time spent in the target zone. (E) Number of entries into the target zone. (F) New arm time. (G) Weight. (H) Cardiac weight index. (I) Renal weight index. Note: NOR—new object recognition experiment; MWM—Morris water maze experiment. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.001.
Figure 3
Figure 3
Effect of BC99 on biochemical indices in chronic sleep deprivation mice (n = 3). (A) The level of CORT in the plasma. (B) The level of NE in the plasma. (C) The level of 5-HT in the hippocampus. (D) The level of DA in the hippocampus. (E) The level of MT in the plasma. (F) The level of blood sugar in the plasma. Note: CORT—corticosterone, NE—norepinephrine, 5-HT—5-Hydroxytryptamine, DA—dopamine, and MT—melatonin. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.001.
Figure 4
Figure 4
Effect of BC99 on the inflammation of brain and plasma in chronic sleep deprivation mice (n = 3). (A) The level of IL-6 in the plasma. (B) The level of TNF-α in the plasma. (C) The level of IL-10 in the plasma. (D) The level of IL-6 in the brain. (E) The level of IL-10 in the brain. Note: (A,D)-interleukin-6; (B)-Tumor necrosis factor-α; (C,E)-interleukin-10. * p < 0.05; ** p < 0.01.
Figure 5
Figure 5
Effect of BC99 on intestinal barrier in chronic sleep deprivation mice. (A) The level of LPS in the plasma. (B) Relative expression of tight junction protein Occludin-1 in the jejunum. (C) Relative expression of tight junction protein ZO-1 in the jejunum. * p < 0.05, ** p < 0.01.
Figure 6
Figure 6
Effects of BC99 on intestinal flora and functional prediction in chronic sleep deprivation mice. α and β diversity in the intestinal flora of mice in each group (A–E). (A) Chao1 index. (B) Shannon index. (C) Goods_coverage. (D) PCA. (E) PCOA. Figure 5 Composition of the mouse intestinal flora at the phylum and genus levels in each group (F,G). (F) Column-stacked plot at the phylum level for relative abundance of TOP30. (G) Heatmap of relative abundance of TOP30 at the genus level. (H) B/F. (I) Venn diagram. Note: (D)—principal component analysis, (E)—principal coordinate analysis, (H)—Hyphomycetes/Phyllobacteriophage, and (I)—Wayne diagram. ** p < 0.01; *** p < 0.001.
Figure 7
Figure 7
Differential effects of BC99 on LEfSe and prediction of PICRUSt2 function in chronic sleep deprivation mice. (A–C): (A) Evolutionary branching diagram. (B) Histogram of LDA distribution. (C) PICRUSt2 function prediction.
Figure 8
Figure 8
Effects of BC99 on short-chain fatty acids and in chronic sleep deprivation mice. (A) The level of acetic acid in the feces. (B) The level of propionic acid in the feces. (C) The level of butyric acid in the feces. (D) The level of isobutyric acid in the feces. (E) The level of valeric acid in the feces. (F) The level of isovaleric acid in the feces. * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 9
Figure 9
Effect of BC99 on NLRP3/ASC inflammasome signaling pathway in the brain and jejunum of chronic sleep-deprived mice. (A–F). (A) Relative expression of NLRP3 in the jejunum. (B) Relative expression of ASC in the jejunum. (C) Relative expression of Caspase-1 in the jejunum. (D) Relative expression of NLRP3 in the brain. (E) Relative expression of ASC in the brain. (F) Relative expression of Caspase-1 in the brain. Note: (A)—crypto thermal protein, (B)—apoptosis-associated speck-like protein, and (C)—cysteinyl aspartate specific proteinase-1. * p < 0.05, ** p < 0.01.
Figure 10
Figure 10
Spearman correlation analysis was used to analyze the correlation between gut microbiota and behavioral tests, SCFAs, brain inflammatory factors, intestinal tight junction proteins, and LPS. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Figure 11
Figure 11
Diagram of the mechanism by which Weizmannia coagulans BC99 improves cognitive impairment in chronic sleep-deprived mice.
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