Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Liu, Zhigang; Dai, Xiaoshuang; Zhang, Hongbo; Shi, Renjie; Hui, Yan; Jin, Xin; Zhang, Wentong; Wang, Luanfeng; Wang, Qianxu; Wang, Danna; Jia, Weiping; Tan, Xiao Di; Ren, Bo; Liu, Xiaoning; Zhao, Tong; Wang, Jiamin; Pan, Junru; Tian, Yuan; Chu, Chuanqi; Lan, Lei; Yin, Fei; Cadenas, Enrique; Shi, Lin; Zhao, Shancen; Liu, Xuebo

doi:10.1038/s41467-020-14676-4

Cited by 332 publications

(380 citation statements)

References 66 publications

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“…We also found that increased Enterococcaceae were part of the small cluster of taxa that corelated with impaired insulin secretion. This result is consistent changes in Enterococcaceae regulating insulin, since intermittent fasting lowers blood insulin and glucose and improved insulin sensitivity, coincident with a decreased relative abundance of Enterococcaceae in obese, diabetic, db/db mice [21]. Furthermore, while bacterial LPS has been shown to impair insulin clearance, we have recently shown that members of the Enterococcaceae family compartmentalize in the tissues of individuals with T2D, independently of obesity [22].…”

Section: Discussionsupporting

confidence: 78%

Gut microbiota impairs insulin clearance during obesity

Foley

Duggan

Barra

et al. 2020

Preprint

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Hyperinsulinemia can be a cause and consequence of obesity and insulin resistance. Increased insulin secretion and reduced insulin clearance can contribute to hyperinsulinemia. The triggers for changes in insulin clearance during obesity are ill-defined. We found that oral antibiotics mitigated impaired insulin clearance in mice fed a high fat diet (HFD) for 12 weeks or longer.Short-term HFD feeding and aging did not alter insulin clearance in mice. Germ-free mice colonized with microbes from HFD-fed mice had impaired insulin clearance, but not C-peptide clearance, and only after mice were colonized for 6 weeks and then HFD-fed. Five bacterial taxa predicted >90% of the variance in insulin clearance. Our data indicate that gut microbes are an independent and transmissible factor that regulates obesity-induced changes in insulin clearance.A small cluster of microbes may be a target for mitigating defects in insulin clearance and the progression of obesity and Type 2 Diabetes. We propose that a small community in the gut microbiota can impair insulin clearance and increase insulin load and the risk of complications from hyperinsulinemia.

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Section: Discussionsupporting

confidence: 78%

Gut microbiota impairs insulin clearance during obesity

Foley

Duggan

Barra

et al. 2020

Preprint

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“…Calorie restriction (CR) has been well documented to mitigate obesity-related metabolic diseases and enhance cognitive performance, promote hippocampal neurogenesis, and regulate clock genes. [17][18][19][20] Methionine (Met), a sulfur-containing amino acid, participates in energy-metabolism homeostasis by acting through several nutritional-response signaling pathways. [21] Notably, Met restriction (MR) represents an improved strategy that produces beneficial effects similar to those induced by CR without the reduction in caloric intake.…”

Section: Introductionmentioning

confidence: 99%

Methionine Restriction Regulates Cognitive Function in High‐Fat Diet‐Fed Mice: Roles of Diurnal Rhythms of SCFAs Producing‐ and Inflammation‐Related Microbes

Wang

Ren

Hui

et al. 2020

Molecular Nutrition Food Res

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Scope Methionine restriction (MR) is known to potently alleviate inflammation and improve gut microbiome in obese mice. The gut microbiome exhibits diurnal rhythmicity in composition and function, and this, in turn, drives oscillations in host metabolism. High‐fat diet (HFD) strongly altered microbiome diurnal rhythmicity, however, the role of microbiome diurnal rhythmicity in mediating the improvement effects of MR on obesity‐related metabolic disorders remains unclear. Methods and results 10‐week‐old male C57BL/6J mice are fed a low‐fat diet or HFD for 4 weeks, followed with a full diet (0.86% methionine, w/w) or a methionine‐restricted diet (0.17% methionine, w/w) for 8 weeks. Analyzing microbiome diurnal rhythmicity at six time points, the results show that HFD disrupts the cyclical fluctuations of the gut microbiome in mice. MR partially restores these cyclical fluctuations, which lead to time‐specifically enhance the abundance of short‐chain fatty acids producing bacteria, increases the acetate and butyric, and dampens the oscillation of inflammation‐related Desulfovibrionales and Staphylococcaceae over the course of 1 day. Notably, MR, which protects against systemic inflammation, influences brain function and synaptic plasticity. Conclusion MR could serve as a potential nutritional intervention for attenuating obesity‐induced cognitive impairments by balancing the circadian rhythm in microbiome‐gut‐brain homeostasis.

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“…Diabetes-induced brain injury manifests as neurodegeneration, cerebral infarction, and progressive cognitive decline. [5][6][7] Evidence arising from diabetic animal models indicates that neuronal death is one of the major factors causing brain injury. 8,9 However, the underlying molecular mechanism of neuronal death in DM is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ‐induced diabetic mice

Che

Yang

et al. 2020

FASEB j.

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Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects against brain damage. However, the effect of melatonin on diabetes‐induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)‐induced diabetic mice and high glucose (HG)‐treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase‐1, GSDMD‐N, IL‐1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA‐214‐3p (miR‐214‐3p) was decreased in DM mice and HG‐treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase‐1 and ATG12. Furthermore, downregulation of miR‐214‐3p abrogated the anti‐pyroptotic and anti‐autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR‐214‐3p/caspase‐1 and miR‐214‐3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.

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Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Cited by 332 publications

References 66 publications

Gut microbiota impairs insulin clearance during obesity

Gut microbiota impairs insulin clearance during obesity

Methionine Restriction Regulates Cognitive Function in High‐Fat Diet‐Fed Mice: Roles of Diurnal Rhythms of SCFAs Producing‐ and Inflammation‐Related Microbes

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ‐induced diabetic mice

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