27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction

Wang, Ying; An, Yu; Ma, Weiwei; Yu, Huiyan; Lu, Yanhui; Zhang, Xiaona; Wang, Yushan; Li, Wen; Wang, Tao; Xiao, Rong

doi:10.1186/s12974-020-01873-7

Cited by 69 publications

(51 citation statements)

References 49 publications

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“…Moreover, it has been reported that an altered gut microbiota composition can influence gut barrier dysfunction, which facilitates the translocation of gut bacteria-derived pathogens and toxins such as lipopolysaccharide (LPS) into the systemic circulation. Consistent with this notion, recent studies showed gut barrier dysfunction and increased gut permeability in mouse models of AD and dementia patients [66][67][68]. Moreover, the integrity of the epithelial gut barrier is reduced with aging and neurodegenerative conditions [69][70][71].…”

Section: Discussionmentioning

confidence: 60%

Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer’s Disease

Shukla

Delotterie

Xiao

et al. 2021

Cells

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Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, is a major cause of death and disability among the older population. Despite decades of scientific research, the underlying etiological triggers are unknown. Recent studies suggested that gut microbiota can influence AD progression; however, potential mechanisms linking the gut microbiota with AD pathogenesis remain obscure. In the present study, we provided a potential mechanistic link between dysbiotic gut microbiota and neuroinflammation associated with AD progression. Using a mouse model of AD, we discovered that unfavorable gut microbiota are correlated with abnormally elevated expression of gut NLRP3 and lead to peripheral inflammasome activation, which in turn exacerbates AD-associated neuroinflammation. To this end, we observe significantly altered gut microbiota compositions in young and old 5xFAD mice compared to age-matched non-transgenic mice. Moreover, 5xFAD mice demonstrated compromised gut barrier function as evident from the loss of tight junction and adherens junction proteins compared to non-transgenic mice. Concurrently, we observed increased expression of NLRP3 inflammasome and IL-1β production in the 5xFAD gut. Consistent with our hypothesis, increased gut–microbial–inflammasome activation is positively correlated with enhanced astrogliosis and microglial activation, along with higher expression of NLRP3 inflammasome and IL-1β production in the brains of 5xFAD mice. These data indicate that the elevated expression of gut–microbial–inflammasome components may be an important trigger for subsequent downstream activation of inflammatory and potentially cytotoxic mediators, and gastrointestinal NLRP3 may promote NLRP3 inflammasome-mediated neuroinflammation. Thus, modulation of the gut microbiota may be a potential strategy for the treatment of AD-related neurological disorders in genetically susceptible hosts.

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Section: Discussionmentioning

confidence: 60%

Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer’s Disease

Shukla

Delotterie

Xiao

et al. 2021

Cells

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“…A complete intestinal mucosal barrier can prevent DAO and D-LA from entering the blood circulation ( Zheng et al., 2020 ). Therefore, the intestinal barrier function can be assessed indirectly by assessing plasma DAO activity and D-LA concentration ( Wang et al., 2020 ). Improving the intestinal mucosal barrier function can reduce DAO activity and D-LA concentration in blood, which has been confirmed by a previous study ( Wu et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

The combined impact of xylo-oligosaccharides and gamma-irradiated Astragalus polysaccharides on growth performance and intestinal mucosal barrier function of broilers

Wang

Xing

et al. 2021

Poultry Science

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This study was conducted to investigate the individual and combined effects of xylo-oligosaccharides ( XOS ) and gamma-irradiated Astragalus polysaccharides ( IAPS ) on the growth performance and intestinal mucosal barrier function of broiler chickens. A total of 240 1-day-old Ross-308 chicks were allocated into 5 groups for 21 d: control group (basal diet), antibiotic growth promoter ( AGP ) group (basal diet supplemented with 50 mg/kg chlortetracycline), XOS group (basal diet supplemented with 100 mg/kg XOS), IAPS group (basal diet supplemented with 600 mg/kg IAPS), and XOS + IAPS group (basal diet supplemented with 100 mg/kg XOS and 600 mg/kg IAPS). The results showed that birds in the XOS + IAPS group showed higher ADG and lower feed-to-gain ratio than those in the control group ( P < 0.05). The XOS, IAPS, and XOS + IASP treatments significantly increased villus height ( VH ) of all intestine segments, jejunal goblet cell numbers, and VH–to–crypt depth ratio ( VH/CD ) of broilers than those of the control group ( P < 0.05). Birds in the XOS + IAPS group had higher jejunal VH/CD ratio and goblet cell numbers than those from the XOS or IAPS groups ( P < 0.05). In addition, there was a synergy effect between XOS and IAPS on increasing duodenal goblet cell numbers and improving ileal morphology (higher VH and VH/CD ratio) ( P < 0.05). The XOS, IAPS and XOS + IAPS treatments increased the mRNA expression of zonula occludens-1 and occludin of the jejunum as compared with the control group ( P < 0.05). Simultaneously, birds in the XOS + IAPS group showed lower plasma D-lactic acid concentration and higher mRNA expression of claudin-1, claudin-3, and occludin in the jejunum than those in the control or IAPS groups ( P < 0.05). Moreover, there was no significant difference in growth performance, intestinal morphology, and intestinal barrier function of broilers between the AGP and XOS + IAPS groups. In conclusion, the combination of XOS and IAPS had a better potential as chlortetracycline substitute for improving the growth performance, intestinal morphology, and intestinal barrier function of broilers.

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“…[30][31][32] When the permeability of the intestine is abnormally increased, the DAO and FITC-dextran in the lumen will pass through the intestinal mucosa easily and go into the peripheral blood. [33][34][35][36] Thus, they are now 3202 usually used to show changes about intestinal permeability. 37 In this study, we have successfully constructed an intestinal barrier dysfunction rats model through burns.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Potential Molecular Targets of Dexmedetomidine in the Intestinal Repair of Burnt Rats

Qin¹,

Jiang²,

Yu³

et al. 2021

JIR

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Background: More and more burn survivors were suffering from varying degrees of damage to the intestinal barrier. Dexmedetomidine (Dex) was frequently used as sedative in more cases, but it was found to have repair effect on intestinal barrier dysfunction recently. This study aimed to explore the potential specific targets of Dex in intestinal barrier repair in burn rats model. Methods: Male adult SD rats were used to establish 40% TBSA III degree scald model in our study. The samples were divided into four groups: burn rats (Burn), burn rats with Dex medication (Burn-Dex), sham rats (Sham) and sham rats with Dex medication (Sham-Dex). And plasma FITC-dextran and diamine oxidase (DAO) were detected to determine the intestinal permeability. Differentially expressed proteins were further adopted to proteinprotein interaction network analysis, Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: It showed that 40% TBSA III degree scald model was successfully constructed. And plasma FITC-dextran and DAO decreased significantly after Dex administration. Additionally, differentially expressed genes Psmb10, Psmb7 among the experimental groups were screened, which were significantly enriched in proteasome and other several pathways. Conclusion:The results above suggested that Q4KM35 and Q9JHW0, which are encoded by Psmb10 and Psmb7, respectively, are two possible protein targets of Dex in intestinal barrier repair.

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27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction

Cited by 69 publications

References 49 publications

Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer’s Disease

Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer’s Disease

The combined impact of xylo-oligosaccharides and gamma-irradiated Astragalus polysaccharides on growth performance and intestinal mucosal barrier function of broilers

Exploration of Potential Molecular Targets of Dexmedetomidine in the Intestinal Repair of Burnt Rats

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