The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

Xu, Youhua; Zhou, Hua; Zhu, Quan

doi:10.3389/fnagi.2017.00106

Cited by 49 publications

(40 citation statements)

References 214 publications

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“…However, the gut–brain axis also mediates the neuroinflammatory response after a vascular injury, such as ischemic stroke 124. Additionally, diabetes mellitus and obesity, which are among the main conditions predisposing to vascular dementia, are both associated with gut microbiota alterations and/or dysbiosis 125,126. Thus, the gut microbiota may also be involved in vascular cognitive impairment, mainly through modulation of local neural and systemic inflammation and insulin sensitivity 127…”

Section: Discussionmentioning

confidence: 99%

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

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

159

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: Discussionmentioning

confidence: 99%

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

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

159

133

View full text Add to dashboard Cite

show abstract

“…In one recently published study the authors found also lower levels of ghrelin in T2DM patients with MCI compared to those with healthy cognition [9]. Other researchers found that ghrelin is an important predictor of executive function impairment in patients with type 2 diabetes [10]. Both studies mention above Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment were performed in much younger population than our study, which the first examine serum ghrelin levels in elderly subjects.…”

Section: Discussionmentioning

confidence: 64%

“…The executive function could be a sensitive indication of diabetic cognitive decline among diabetes population. The author proposed that serum ghrelin level might be a biomarker of executive function in patients with type 2 diabetes mellitus [10].…”

Section: Discussionmentioning

confidence: 99%

“…The chronic inflammation could be provoked and sustained by changes in the gut microbiota composition. This phenomenon is called "gut-brain axis" and it incorporates bidirectional communication between the central nervous system and the gastrointestinal system [9,10]. Strong objective evidence of a linkage between gut bacteria and brain function comes from several human and animal studies [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Both dysbacteriosis in the gut and higher systemic inflammation in diabetic population can lead to the intestinal barrier and blood brain barrier dysfunction. Thus harmful substances such as advanced glycation end products, pathogens, endoxin with easy access to neurons, can cause neuroinflammation and the development of cognitive decline [10].…”

Section: Introductionmentioning

confidence: 99%

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Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

Górska-Ciebiada¹,

Cypryk²,

Borkowska³

et al. 2018

Neuropsychiatry

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Objective:The etiology of cognitive impairment in diabetes is unknown, but probably associated with many factors. One of the recent hypotheses suggests that ghrelin could be involved in cognitive impairment in diabetic patients. It has been reported that ghrelin signaling occurs in the hippocampus and improves memory and spatial learning. The aim of this study was to evaluate serum levels of ghrelin in elderly, diabetic patients with and without mild cognitive impairment (MCI) and to determine the predictors of having MCI in elderly diabetics. Methods:The cross-sectional study was conduct among 276 elderly subjects with type 2 diabetes. 87 patients with MCI and 189 controls were selected according to the criteria proposed by the MCI Working Group of the European Consortium on Alzheimer's Disease (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. The serum levels of ghrelin were assessed using ELISA kit. Results:Serum levels of ghrelin were significantly lower in patients with MCI compared to controls. In MCI patients serum ghrelin levels were positively correlated with MoCA score and negatively correlated with HbA1c and BMI. The logistic regression models revealed that variables which increased the likelihood of diagnosis of MCI in elderly diabetic patients were: lower levels of ghrelin, higher levels of HbA1c, hypertension, previous cardiovascular disease, increased number of co-morbidities, and less years of formal education. Conclusion:In summary, serum levels of ghrelin were decreased in MCI elderly diabetic patients compared to controls and associated with poor MoCA score. The results indicated that lower ghrelin levels may be a risk factor for a cognitive impairment in diabetic, elderly patients. Further prospective larger studies are needed to confirm the role of this marker in the progression to dementia.

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Cognitive protection of sinomenine in type 2 diabetes mellitus through regulating the EGF/Nrf2/HO‐1 signaling, the microbiota‐gut‐brain axis, and hippocampal neuron ferroptosis

Chen

Guo

Han

et al. 2023

Phytotherapy Research

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Recent years have witnessed a growing research interest in traditional Chinese medicine as a neuroprotective nutrient in the management of diabetic cognitive dysfunction. However, the underlying molecular mechanisms of sinomenine in mediating ferroptosis of hippocampal neurons have been poorly understood. This study sought to decipher the potential effect and molecular mechanism of sinomenine in the cognitive dysfunction following type 2 diabetes mellitus (T2DM). Multi-omics analysis was conducted to identify the microbiota-gut-brain axis in T2DM patient samples obtained from the publicly available database. In HT-22 cells, erastin was utilized to create a ferroptosis model, and streptozotocin was injected intraperitoneally to create a rat model of DM. It was noted that intestinal flora imbalance occurred in patients with T2DM-associated cognitive dysfunction. Sinomenine could reduce Erastin-induced hippocampus neuronal ferroptosis by increasing EGF expression.EGF protected hippocampal neurons against ferroptosis by activating the Nrf2/HO-1 signaling pathway. Furthermore, in vivo results confirmed that sinomenine blocked ferroptosis of hippocampal neurons and alleviated cognitive dysfunction in T2DM rats. Collectively, these results suggest that sinomenine confers neuroprotective effects by curtailing hippocampal neuron ferroptosis via the EGF/Nrf2/HO-1 signaling and microbiota-gut-brain axis. It may be a candidate for the treatment of diabetic cognitive dysfunction.

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The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

Cited by 49 publications

References 214 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

Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

Cognitive protection of sinomenine in type 2 diabetes mellitus through regulating the EGF/Nrf2/HO‐1 signaling, the microbiota‐gut‐brain axis, and hippocampal neuron ferroptosis

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