Distinctive subgingival microbial signatures in older adults with different levels of cognitive function.

AIM: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. MATERIALS AND METHODS: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). RESULTS: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. CONCLUSIONS: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.

Investigating the association between inflammation mediated by mushroom consumption and mild cognitive impairment in Chinese older adults.

Background: Chronic inflammatory stimulation is a major risk factor for mild cognitive impairment. Mushroom consumption and inflammatory factors may play an important role in the pathogenesis of mild cognitive impairment. Additionally, consuming mushrooms can reduce the levels of inflammatory cytokines and preserve cognitive function. Therefore, this study aimed to investigate the relationship between mushroom consumption and serum inflammatory cytokines and mild cognitive impairment (MCI). Methods: Binary logistic regression was used to determine the relationship between mushroom consumption and MCI in 550 participants. Subsequently, mediation analysis was used to analyze the relationship between mushroom consumption, inflammatory factors, and the Montreal Cognitive assessment (MoCA) score in 248 participants. Results: Mushroom consumption was associated with MCI (odds ratio = 0.623, 95% confidence interval = 0.542-0.715, P < 0.001). The association between mushroom intake and MCI was mediated by interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP), and the MoCA score was 12.76% and 47.59%, respectively. Conclusion: A high intake of mushrooms was associated with a low risk of MCI. Serum inflammatory factors including IL-6 and hs-CRP play a partial mediating role between mushroom intake and the MoCA score, and the underlying mechanism needs to be further explored.

Energy-adjusted dietary inflammatory index and cognitive function in Chinese older adults: a population-based cross-sectional study.

Diet can regulate systemic inflammation, which may play an important role in the development and progression of cognitive impairment and dementia. To explore the relationship between the dietary inflammatory potential and cognitive ability. A total of 2307 adults aged 60 years or older were recruited from the Fujian Provincial Hospital (Fujian, China). Dietary inflammatory properties were analyzed using the energy-adjusted dietary inflammatory index (E-DII). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. Logistic regression and restricted cubic spline (RCS) were fit to assess the associations between variables. The MCI subjects with the highest E-DII scores had a higher risk of AD compared to subjects with the lowest E-DII scores (OR = 1.98, 95%CI = 1.49-2.64, P for trend < 0.001). Subjects with the highest E-DII levels were at increased risk of cognitive impairment compared to those with the lowest E-DII levels (OR = 1.56, 95%CI = 1.25-1.93, P for trend < 0.001). The link between E-DII and cognitive impairment was significant in a nonlinear dose response analysis (P for nonlinear = 0.001). Higher E-DII scores were associated with an increased risk of developing AD or cognitive impairment. These findings may contribute to the effective prevention of cognitive impairment by constructing a multidisciplinary synergistic prevention strategy and controlling dietary inflammation levels.

Different oral and gut microbial profiles in those with Alzheimer's disease consuming anti-inflammatory diets.

The number of people living with Alzheimer's disease (AD) is increasing alongside with aging of the population. Systemic chronic inflammation and microbial imbalance may play an important role in the pathogenesis of AD. Inflammatory diets regulate both the host microbiomes and inflammatory status. This study aimed to explore the impact of inflammatory diets on oral-gut microbes in patients with AD and the relationship between microbes and markers of systemic inflammation. The dietary inflammatory properties and the oral and gut microorganisms were analyzed using the dietary inflammatory index (DII) and 16S RNA in 60 patients with AD. The α-diversity was not related to the DII (p > 0.05), whereas the ß-diversity was different in the oral microbiomes (R2 = 0.061, p = 0.013). In the most anti-inflammatory diet group, Prevotella and Olsenella were more abundant in oral microbiomes and Alistipes, Ruminococcus, Odoribacter, and unclassified Firmicutes were in the gut microbiomes (p < 0.05). Specific oral and gut genera were associated with interleukin-6 (IL)-6, complement 3 (C3), high-sensitivity C-reactive protein (hs-CRP), IL-1ß, IL-4, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) (p < 0.05). In conclusion, anti-inflammatory diets seem to be associated with increased abundance of beneficial microbes, and specific oral and gut microbial composition was associated with inflammatory markers.

Effects of oral health intervention strategies on cognition and microbiota alterations in patients with mild Alzheimer's disease: A randomized controlled trial.

We explored the effects of an oral health intervention on the oral microbiome and cognitive function of patients with mild Alzheimer's disease (AD) and determined the influence on disease progression. Sixty-six patients with mild AD were randomly assigned to intervention or control groups and received a 24-week oral health intervention and routine care, respectively. Data were collected at baseline and week 24. 16 S rRNA sequencing was used to analyze oral microbiota. After 24 weeks of oral health intervention, Kayser-Jones Brief Oral Health Status Examination (BOHSE), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Nursing Home Adjustment Scale (NHAS), and Alzheimer's Disease Cooperative Study-ADL (ADCS-ADL) scores were different between groups (p < 0.05). Subgingival plaque in patients with AD showed significant differences in the diversity and abundance of oral microbiomes, with a higher abundance of normal oral flora in the intervention group. We found oral health intervention strategies are effective in modifying subgingival microbiota differences and slowing cognitive decline in mild AD patients.

A comparison of the composition and functions of the oral and gut microbiotas in Alzheimer's patients.

Objective: Alterations in the oral or gut microbiotas have been reported in patients with subjective and mild cognitive impairment or AD dementia. However, whether these microbiotas change with the severity of the AD spectrum (mild, moderate, and severe AD) remains unknown. Thus, we compared alterations in the composition and gene functions of the oral and gut microbiota between different phases of AD. Methods: We recruited 172 individuals and classified these into three groups: healthy controls (n = 40), a mild AD group (n = 43) and a moderate AD group (n = 89). Subgingival plaques and fecal samples were collected from all individuals. Then, we conducted 16S ribosomal RNA. sequencing to analyze the microbiotas. Results: In order of the severity of cognition impairment (from normal to mild and to moderate AD), the oral abundances of the phyla Firmicutes and Fusobacteria showed a gradual upwards trend, while the abundance of the Proteobacteria phylum gradually decreased. In contrast, the abundance of the Firmicutes and Bacteroidetes phyla in the gut decreased progressively, while that of the Proteobacteria, Verrucomicrobia and Actinobacteria phyla increased gradually. Key differences were identified in the microbiomes when compared between the mild AD and moderate AD groups when applying the linear discriminant analysis effect size (LEfSe) algorithm. LEfSe analysis revealed alterations that were similar to those described above; furthermore, different bacterial taxa were associated with MMSE scores and age. KEGG analysis showed that the functional pathways associated with the oral microbiota were mainly involved in membrane transport and carbohydrate metabolism, while the gene functions of the fecal microbiota related to metabolism of amino acids, energy, cofactors and vitamins; identified significant differences among the three groups. Venn diagram analysis revealed that the number of genera that were present in both the oral and gut microbiota increased progressively from NC to mild AD and then to moderate AD. Conclusions: This study is the first to report a comparative analysis of the oral and fecal microbiota of patients with mild and moderate AD. The compositions and functions of the oral and gut microbiotas differed when compared between different stages of AD.

High level of lncRNA NR2F1-AS1 predict the onset and progression of diabetic retinopathy in type 2 diabetes.

This study aimed to investigate whether dysregulation of NR2F1-AS1 is associated with the T2D onset and DR progression. A total of 269 individuals diagnosed with T2D were recruited in this study, including 111 individuals with uncomplicated T2D and 158 individuals with nonproliferative diabetic retinopathy (NPDR). A total of 48 among the NPDR individuals developed into proliferative diabetic retinopathy (PDR), excepting that 6 individuals were dropped out. RT-qPCR was used to determine the expression of NR2F1-AS1 level in blood. The correlations between NR2F1-AS1 expression and other parameters were tested by Pearson correlation. Receiver operating characteristic (ROC) curves were plotted for evaluating the diagnostic value of NR2F1-AS1 as a biochemical indicator detecting T2D and PDR. Kaplan-Meier method and Cox multivariable analysis was used to evaluate the predictive power of NR2F1-AS1 for incidence of PDR. A significant increase in blood NR2F1-AS1 in uncomplicated T2D, NPDR, and PDR patients was found when compared to healthy subjects. Significant correlations between NR2F1-AS1 expression and the level of fasting glucose, 2-h postprandial blood glucose, and HbA1c were revealed. Furthermore, NR2F1-AS1 represented distinguishing ability in T2D individuals from healthy subjects and PDR individuals from NPDR individuals. NR2F1-AS1 also showed strong predictive ability for PDR. The examination of blood NR2F1-AS1 may be used as a noninvasive biomarker for screening of T2D and early diagnosis of DR. NR2F1-AS1 may also be used as a promising novel biomarker for prediction PDR. NR2F1-AS1 may play a role in the progression of DR by moderating EndMT.

Dysregulation of miR-210 is involved in the development of diabetic retinopathy and serves a regulatory role in retinal vascular endothelial cell proliferation.

BACKGROUND: Diabetic retinopathy is a common complication of diabetes mellitus (DM). The purpose of this study was to investigate the expression and clinical significance of miR-210 in DR patients and explore the regulatory effect of miR-210 on vascular endothelial cell function under high-glucose condition. METHODS: Quantitative real-time PCR was used to estimate miR-210 expression. A receiver operating characteristics curve (ROC) was plotted to evaluate the diagnostic value of miR-210. Human umbilical vein endothelial cells (HUVECs) were used and treated with high glucose (30 mM), and the cell proliferation was assessed by MTT assay. RESULTS: Serum expression of miR-210 was upregulated in DR patients compared with DM without DR patients and healthy controls. The expression of miR-210 in proliferative DR (PDR) patients was higher than non-proliferative DR (NPDR) patients. The increased serum miR-210 could be used to distinguish DR cases from healthy individuals and also simple DM patients, and can screen PDR cases from NPDR cases. The overexpression of miR-210 promoted HUVEC proliferation, while the knockdown of miR-210 resulted in the opposite effect under a high-glucose condition. CONCLUSION: The data of this study demonstrated that serum increased miR-210 serves as a diagnostic biomarker in DR patients and may have the ability to predict DR development and severity. The regulatory effect of miR-210 on vascular endothelial cell proliferation under high-glucose condition, indicating its therapeutic potential in the treatment of diabetic vascular diseases.