Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Peng, Weijun; Yi, Pan; Yang, Jingjing; Xu, Panpan; Wang, Yang; Zhang, Zheyu; Huang, Siqi; Wang, Zhe; Zhang, Chunhu

doi:10.18632/aging.101693

Cited by 64 publications

(56 citation statements)

References 44 publications

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“…Multiple researches indicate that microbial colonization of the gut is linked to dementia pathogenesis via detrimental effects on metabolic disorders or low-grade inflammation progress, leading to damage to the brain [33] . Consistent with previous studies [34] , our findings provided further evidence that the microbiota-gut-brain axis may be involved in AD-like pathogenesis in SAMP8. PCoA and microbiota composition analysis revealed that the cluster from salidroside-treated SAMP8 was more similar to that of SAMR1, whereas the cluster from untreated SAMP8 was the most distinct.…”

Section: Discussionsupporting

confidence: 92%

Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) and Modulating Inflammation on the Gut-brain Axis

Xie

Lü

Yang

et al. 2020

Preprint

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Background Alzheimer’s disease (AD), as the most prime cause of dementia, is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, A range of therapeutic approaches have shown unsatisfactory outcomes in clinical setting. Thus, it is critical to develop alternative therapies for the treatment of AD. Salidroside(SAL), a herb-derived phenylpropanoid glycoside compound, has been shown to attenuate LPS-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here we show a therapeutic effect of SAL in a reliable and stable mouse model of AD, Senescence-Accelerated Mice Prone 8 (SAMP8).Methods SAMP8 were treated with salidroside, donepezil or saline, cognitive behavioral impairments were assessed using the Morris water maze, Y-maze, and open-field tests. Fecal samples were collected and analyzed by 16S rRNA sequencing, performed on the Illumina MiSEq. Brain samples were analyzed by immunohistochemistry and western blot to detect Beta Amyloid 1–42 deposition. Activation in microglia and neuroinflammatory cytokines was detected by immunofluorescence, Western blot and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel and performed on the Luminex-MAGPIX multiplex immunoassay system.Results Our results suggested that SAL effectively alleviated hippocampus-dependent memory impairment in SAMP8, and showed no significant difference compared with the donepezil-administration group. SAL significantly (1) reduced toxic beta-amyloid (Abeta) 1–42 deposition; (2) reduced activation of microglia and attenuated proinflammatory factors, IL-1β, IL-6, and TNF-α, in the brain; (3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes, and eliminated Clostridiales and Streptococcaceae, which may have been associated with cognitive deficits); and (4) decreased the levels of proinflammatory cytokines in the peripheral circulation, IL-1α, IL-6, IL-17A and IL-12 in particular, according to a multiplex immunoassay.Conclusion In summary, SAL reversed AD-related changes in SAMP8 potentially through the regulation of the microbiota-gut-brain axis and by modulating inflammation in both peripheral circulation and central nervous system. Our results strongly suggest a therapeutic effect of SAL on cognition-related changes in SAMP8 and highlight its value as a potential source for drug development.

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Section: Discussionsupporting

confidence: 92%

Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) and Modulating Inflammation on the Gut-brain Axis

Xie

Lü

Yang

et al. 2020

Preprint

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“…Similarly to SCZ, the inflammatory patterns in BD are characterised by increased levels of TNF-α, the soluble TNF receptor type 1 (sTNF-R1) and the soluble IL-2 receptor (sIL-2R) compared with HC 48. Of note, there are intriguing findings, although still at the level of experimental preclinical data, suggesting that perturbations of the gut microbiota composition and the functional metagenome may be associated with accelerated ageing in animal models 49. In summary, the literature shows that: (1) there is a plausible interaction between inflammation and TS in modulating the risk of severe psychiatric disorders, and (2) this association might reflect (or be modulated) by specific detrimental alterations of the microbiota.…”

Section: Discussionmentioning

confidence: 99%

A multidisciplinary approach to mental illness: do inflammation, telomere length and microbiota form a loop? A protocol for a cross-sectional study on the complex relationship between inflammation, telomere length, gut microbiota and psychiatric disorders

et al. 2020

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IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.

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“…cardiovascular diseases, tumors, Alzheimer's disease, CKD etc.) which may also in uence abundance and diversity of gut microbiota [7,[25][26][27][28]. The correlation between gut microbiota composition and lifestyle or speci c medications need to be further clari ed at the same time.…”

Section: Discussionmentioning

confidence: 99%

“…Disruption of this stable ecosystem, characterized by increased potential pathogens or decreased "bene cial" bacteria, probably implies imbalance induced by disease. Accumulating researches have suggested that potential function of gut microbiome is closely related to fatty acid metabolism, oxidative stress resistance, regulation of insulin sensitivity in diabetes, as well as arteriosclerosis and thrombosis in atherosclerotic diseases [5][6][7][8]. Moreover, approach using microbial markers for diseases identi cation has been proposed and proven feasible.…”

mentioning

confidence: 99%

Gut microbiome alterations predict diabetic kidney disease in general population

Zhao¹,

Zhang²,

Guo³

et al. 2020

Preprint

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Background Diabetic kidney disease (DKD) is increasingly prevalent owing to worldwide epidemic of diabetes mellitus (DM). The relationship between gut microbiome and chronic kidney disease (CKD) has attached wide attention during recent years. While the role of gut microbiome in diagnosis of DKD remains unclear. Methods We collected fecal samples of 180 patients with DKD and 179 healthy controls (Con) and characterized microbial profile using 16S rRNA gene sequencing approach. Microbial communities between the two groups were compared by Wilcoxon test. Two microbial models were identified by cross-validation preformed on random forest analysis. Diagnostic value of the two models was assessed in the training set including 118 DKDs and 132 healthy controls and validated in testing set composed of 62 DKDs and 47 healthy controls. PICRUSt was exploited to compare the potential metabolic function of microbiota between two groups. Results Compared with healthy controls, bacterial diversity in DKDs was decreased. Beta diversity showed markedly separating distribution between DKDs and Con groups. At the phylum level, DKD patients showed higher proportion of Proteobacteria, Verrucomicrobia and lower proportion of Bacteroidetes. In more details at the genus level, increase of opportunistic pathogens (including Escherichia-Shigella, Klebsiella, Enterococcus, Erysipelotrichaceae_incertae_sedis, Peptostreptococcaceae_incertae_sedis, Streptococcus) and mucin-degrading bacteria (including Akkermansia, Lactobacillus),as well as reduction of bacteria producing short-chain fatty acids (SCFA) such as Blautia༌Faecalibacterium were also observed in DKDs. The optimal prediction model consisting of 5 OTUs could distinguish DKD from healthy controls with an area under the ROC curve of 83.71% in training set and 81.56% in testing set, while another 22 OTUs couldn’t significantly improve diagnostic efficiency. Genomic metabolism associated with lipid and aromatic amino acids was over-expressed in DKD vs. Con. Conclusion Gut microbiome was altered in DKD patients. Our study suggested that gut microbiome may provide a potential tool for DKD diagnosis, especially those who could not accept or afford renal biopsy.

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Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Cited by 64 publications

References 44 publications

Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) and Modulating Inflammation on the Gut-brain Axis

Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) and Modulating Inflammation on the Gut-brain Axis

A multidisciplinary approach to mental illness: do inflammation, telomere length and microbiota form a loop? A protocol for a cross-sectional study on the complex relationship between inflammation, telomere length, gut microbiota and psychiatric disorders

Gut microbiome alterations predict diabetic kidney disease in general population

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