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Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline.

ABSTRACT: The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer's pathology in mouse models. To elucidate the molecular mechanisms underlying the preventive effects of fermented dairy products, we screened peptides from digested milk protein for their potential to regulate the activation of microglia. We identified dipeptides of tryptophan-tyrosine (WY) and tryptophan-methionine that suppressed the microglial inflammatory response and enhanced the phagocytosis of amyloid-? (A?). Various fermented dairy products and food materials contain the WY peptide. Orally administered WY peptide was smoothly absorbed into blood, delivered to the brain, and improved the cognitive decline induced by lipopolysaccharide via the suppression of inflammation. Intake of the WY peptide prevented microglial inflammation, hippocampal long-term potential deficit, and memory impairment in aged mice. In an Alzheimer's model using 5×FAD mice, intake of the WY peptide also suppressed microglial inflammation and accumulation of A?, which improved cognitive decline. The identified dipeptides regulating microglial activity could potentially be used to prevent cognitive decline and dementia related to inflammation.

SUBMITTER: Ano Y

PROVIDER: S-EPMC6555451 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline.

Ano Yasuhisa Y Yoshino Yuka Y Kutsukake Toshiko T Ohya Rena R Fukuda Takafumi T Uchida Kazuyuki K Takashima Akihiko A Nakayama Hiroyuki H

Aging 20190501 10

The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer's pathology in mouse models. To elucidate the molecular mechanisms underlying the preventive effects of fermented dairy products, we screened peptides from digested milk ...[more]

PMID: 31121563

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Project description:Fermented dairy foods (FDFs) and probiotics are promising tools for the prevention and management of cardiometabolic diseases (CMDs), respectively. The relation between the regular consumption of FDFs and CMD risk factors was assessed by prospective cohort studies (PCSs), and the effect of probiotic supplementation added into a dairy matrix on CMD parameters was evaluated by randomized controlled trials (RCTs). Moreover, the effects of probiotic supplementation added into a dairy matrix were compared with those administered in capsule/powder form. Twenty PCSs and 52 RCTs met the inclusion criteria for the systematic review and meta-analysis. In PCSs, fermented milk was associated with a 4% reduction in risk of stroke, ischemic heart disease, and cardiovascular mortality [RR (95% CI); 0.96 (0.94, 0.98)]; yogurt intake was associated with a risk reduction of 27% [RR (95% CI); 0.73 (0.70, 0.76)] for type 2 diabetes (T2D) and 20% [RR (95% CI); 0.80 (0.74, 0.87)] for metabolic syndrome development. In RCTs, probiotic supplementation added into dairy matrices produced a greater reduction in lipid biomarkers than when added into capsules/powder in hypercholesterolemic subjects, and probiotic supplementation by capsules/powder produced a greater reduction in T2D biomarkers than when added into dairy matrices in diabetic subjects. Both treatments (dairy matrix and capsules/powder) resulted in a significant reduction in anthropometric parameters in obese subjects. In summary, fermented milk consumption is associated with reduced cardiovascular risk, while yogurt intake is associated with a reduced risk of T2D and metabolic syndrome development in the general population. Furthermore, probiotic supplementation added into dairy matrices could be considered beneficial for lowering lipid concentrations and reducing anthropometric parameters. Additionally, probiotic capsule/powder supplementation could contribute to T2D management and reduce anthropometric parameters. However, these results should be interpreted with caution due to the heterogeneity of the studies and the different probiotic strains used in the studies. This trial is registered with PROSPERO (CRD42018091791) and the protocol can be accessed at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018091791.

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Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline.

Publications

Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline.

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