Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease

Zhang, Ling; Wang, Ying; Xia, Xiayu; Shi, Changhua; Chen, Wei; Song, Nan; Fu, Xinjing; Zhou, Rui; Xu, Yanfeng; Huang, Lan; Zhu, Hua; Han, Yunlin; Qin, Chuan

doi:10.3233/jad-170020

Cited by 365 publications

(221 citation statements)

References 66 publications

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“…Interestingly, amyloid deposition was also observed in the gut tissue of murine AD models and it correlated with dysbiosis 46. In a recent observational study, mice genetically prone to AD exhibited a distinct fecal microbiota composition than healthy controls, with reduced biodiversity and altered functionality 47. Especially, the production of SCFAs by the gut microbiota was reduced, with possible negative effects on amyloid deposition in both the brain and the gut 47…”

Section: Resultsmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

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Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

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Section: Resultsmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

View full text Add to dashboard Cite

show abstract

“…Quantification analysis of fecal SCFAs was performed using an Agilent 7890A gas chromatography coupled with an Agilent 5975C mass spectrometric detector (Agilent Technologies, USA) equipped with an HP-5MS column (0.25 × 30 mm, 0.25 μm particlesize) (Suzhou Bionovogene Co., Ltd) as described previously [21]. Helium was used as a carrier gas at a constant flow rate of 1 mL/min.…”

Section: Fecal Scfas Quantification By Gas Chromatography-mass Spectrmentioning

confidence: 99%

Dietary flaxseed oil rich in omega-3 suppresses severity of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in rats

et al. 2020

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Background: Type 2 diabetes mellitus (T2DM) is closely associated with hyperglycemia, abnormal lipid profiles, chronic low-grade inflammation and gut dysbiosis. Dietary intervention plays a crucial role in the control of diabetes. Flaxseed oil (FO), a plant-derived omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), is rich in α-linolenic acid (ALA) which has been proved to benefit for chronic metabolic disease. However, the exact effects of dietary FO on T2DM remains largely unclear.Methods: In the present study, SD rats were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); DM with CO group (DM/CO); PF with FO group (PF/FO); DM with FO group (DM/FO). A diabetic rat model was generated by a single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NA). After 5 weeks of intervention, rats were euthanized and associated indications were investigated.Results: Dietary FO significantly reduced fasting blood glucose (FBG), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-17A and malondialdehyde (MDA), compared to control group, respectively. Moreover, body mass (BM) and superoxide dismutase (SOD) in DM/FO group were dramatically increased respectively, compared with those in DM/CO group. But insulin (INS) and homeostasis model assessment of insulin resistance (HOMA-IR) remained no significant difference between DM/CO group and DM/FO group. Sequencing analysis of gut microbiota showed a reduction in the relative abundance of Firmicutes and Blautia, as well as a reduction in the ratio of Bacteroidetes-Firmicutes in DM/FO group compared to DM/CO group. An elevation in the relative abundance of Bacteroidetes and Alistipes were detected in DM/FO group. Acetic acid, propionic acid and butyric acid belonging to short chain fatty acids (SCFAs) as gut microbiota metabolites, were dramatically increased after FO intervention. Correlation analysis revealed that the relative abundance of Firmicutes and Blautia were positively correlated with IL-1β, TNF-α, IL-6, IL-17A or LPS, respectively. Additionally, Bacteroidetes and Alistipes were negatively correlated with LPS.Conclusions: Taken together, dietary FO ameliorated T2DM via suppressing inflammation and modulating gut microbiota, which may potentially contribute to dietary control of diabetes.

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“…In addition, other extra-gastrointestinal diseases such as atherosclerosis, metabolic syndrome, hypertension, type 2 diabetes, and neuromusculoskeletal diseases (i.e., cachexia and frailty) are also associated with gut dysbiosis (3,11,(17)(18)(19)(20)(21). Imbalance of the gut microbiome is also associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease (22)(23)(24)(25) and multiple sclerosis (26,27) (Figure 1). Remarkably, some of these diseases are involved in the onset of cognitive frailty (3,4).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

et al. 2020

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Cognitive frailty is a geriatric condition defined by the coexistence of cognitive impairment and physical frailty. This "composite" aging phenotype is associated with a higher risk of several adverse health-related outcomes, including dementia. In the last decade, cognitive frailty has gained increased attention from the scientific community that has focused on understanding the clinical impact and the physiological and pathological mechanisms of development and on identifying preventive and/or rehabilitative therapeutic interventions. The emergence of gut microbiome in neural signaling increased the interest in targeting the gut-brain axis as a modulation strategy. Multiple studies on gastroenteric, metabolic, and neurodegenerative diseases support the existence of a wide bidirectional communication network of signaling mediators, e.g., bioactive lipids, that can modulate inflammation, gut permeability, microbiota composition, and the gut-brain axis. This crosstalk between the gut-brain axis, microbiome, and bioactive lipids may emerge as the basis of a promising therapeutic strategy to counteract cognitive frailty. In this review, we summarize the evidence in the literature regarding the link between the gut microbiome, brain, and several families of bioactive lipids. In addition, we also explore the applicability of several bioactive lipid members as a potential routes for therapeutic interventions to combat cognitive frailty.

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Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease

Cited by 365 publications

References 66 publications

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Dietary flaxseed oil rich in omega-3 suppresses severity of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in rats

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

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