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BACKGROUND: Age-related dysbiosis of the microbiota has been linked to various negative health outcomes. This study aims to investigate the effects of a newly discovered dietary fiber compound (DFC) on aging, intestinal microbiota, and related metabolic processes. The DFC was identified through in vitro fermentation screening experiments, and its dosage and composition were determined based on a longevity dietary pattern. METHODS: Aged SPF C57BL/6 J mice (65 weeks old) and young mice (8 weeks old) were divided into three groups: a subgroup without dietary fiber (NDF), a low DFC dose subgroup (LDF, 10% DFC), and a high DFC dose subgroup (HDF, 20% DFC). The total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity in liver and serum samples of the mice were measured according to the manufacturer's protocol. The expression levels of characteristic bacterial genera and fecal metabolite concentrations in mice were determined using quantitative real-time PCR (qPCR) and nuclear magnetic resonance hydrogen spectroscopy (1H NMR). Metabolomics analysis was further conducted to identify biological functions and potential pathways related to aging. RESULTS: After an 8-weeks dietary intervention, DFC supplementation significantly attenuated age-related weight loss, organ degeneration, and oxidative stress. And promoted the growth of Lactobacillus and Bifidobacterium and inhibited the growth of Escherichia coli (E. coli) and Bacteroides (p < 0.05) in the intestinal tracts of aged mice. Metabolomic analysis identified glycolipid and amino acid metabolic pathway biomarkers associated with aging that were differentially regulated by DFC consumption. Correlation analysis between the identified microbial flora and the biomarkers revealed potential mechanistic links between altered microbial composition and metabolic activity with aging markers. CONCLUSIONS: In conclusion, this study revealed an important mechanism by which DFC consumption impacts healthspan and longevity, shedding light on optimizing dietary fiber or developing fiber-based interventions to improve human health.
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The feces of healthy middle-aged and old people were first transplanted into d-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.
Assuntos
Envelhecimento , Bifidobacterium bifidum , Fezes , Galactose , Microbioma Gastrointestinal , Lacticaseibacillus casei , Probióticos , Animais , Lacticaseibacillus casei/metabolismo , Humanos , Camundongos , Probióticos/administração & dosagem , Probióticos/farmacologia , Bifidobacterium bifidum/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Fezes/química , Masculino , Transplante de Microbiota Fecal , Pessoa de Meia-Idade , Feminino , Idoso , Camundongos Endogâmicos C57BL , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismoRESUMO
With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes, Bacteroides, Blautia, Lachnospiraceae NK4A136 group, and Lactobacillus, were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis, were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.
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Microbioma Gastrointestinal , Probióticos , Humanos , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , China , Envelhecimento/fisiologiaRESUMO
A series of previous studies by our team has shown that the Guangxi longevity dietary pattern contributes to the improvement of human health, but the role of dietary fiber compounds (DFC) in the anti-aging of this dietary pattern has not been studied in depth. Thus, mice were fed with 5%, 15%, and 30% of the characteristic dietary fiber compound (CDFC) (compounded according to the longevity dietary pattern) for 8 weeks, and their learning memory capacity, antioxidant capacity, and inflammatory markers, as well as typical microorganisms in the intestinal tract were analyzed to investigate the anti-aging effects of the CDFC under the Guangxi longevity dietary pattern on naturally aging mice. The results showed that CDFC had a bidirectional effect on body weight regulation; increased brain, spleen, and cardiac indices, of which the medium dose was the best. Meanwhile, CDFC also had a maintenance and improvement effect on learning and memory ability in aging mice, as well as improved antioxidant capacity and reduced inflammation level. The neuronal cell necrosis in the hippocampus of mice was effectively alleviated. The expression of Escherichia coli and Bacteroides was significantly reduced, and the expression of Bifidobacterium and Lactobacillus increased. In addition, the optimal amount of CDFC added from the level of experimental animals was in a certain interval above and below 15%. The combined results indicated that CDFC mediated by the Guangxi longevity dietary pattern had significant anti-aging effects, thus theoretically proving that dietary fiber compound contributes to human longevity.
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Antioxidantes , Longevidade , Envelhecimento , Animais , Antioxidantes/farmacologia , China , Fibras na Dieta/farmacologia , Humanos , CamundongosRESUMO
The purpose of this study was to investigate the effects of different dietary fiber compounds (DFCs) on characteristic human flora and their metabolites mediated by the longevity dietary pattern analyzed by in vitro fermentation. The results show that DFC1 (cereal fiber) increased the level of Lactobacillus (p < 0.05), DFC2 (fruit and vegetable and cereal fiber) promoted the growth of Lactobacillus and Bifidobacterium more significantly than DFC3 (fruit and vegetable fiber) (p < 0.01), and all three DFCs decreased the level of Escherichia coli (p < 0.05). The metabolomic analysis showed that there was variability in the metabolites and the metabolic pathways of different DFCs. The redundancy analysis revealed that the fiber content was positively correlated with Lactobacillus, Bifidobacterium, Bacteroides, acetic acid, butyric acid, propionic acid, lactic acid, and betaine, and negatively correlated with Escherichia coli, succinic acid, alanine, choline, aspartic acid, and α-glucose. Overall, this study found that different DFCs have different positive correlations on characteristic human flora and metabolites, and DFC2 is more favorable to the proliferation of the intestinal beneficial genera Lactobacillus and Bifidobacterium after in vitro fermentation, having a probiotic role in glucose, amino acid, and lipid metabolisms. This study may provide a theoretical reference for the search of optimal dietary fiber combination strategies mediated by longevity dietary pattern.
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Fibras na Dieta , Ácidos Graxos Voláteis , Humanos , Ácidos Graxos Voláteis/metabolismo , Fibras na Dieta/análise , Fermentação , Bifidobacterium/metabolismo , Lactobacillus/metabolismo , Escherichia coli/metabolismo , Glucose/metabolismoRESUMO
The phenomenon of longevity in Guangxi of China proved to be closely relevant to its specific dietary habits, but the exact effects of this diet on health remain to be explored. In this work, fourteen screened volunteers with cardiovascular disease (CVD) risk followed a novel dietary pattern derived from centenarians of Guangxi, China for 2 weeks, then the effects of diet on human health were explored by measuring the health metrics and fecal metabolites. The results showed that the short-term dietary intervention significantly decreased the body weight, body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), mean systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, while it significantly increased high-density lipoprotein cholesterol (HDL-c) levels. Orthogonal partial least squares discriminant analysis (OPLS-DA) indicated a distinct separation in the fecal metabolic profiles of volunteers before and after the intervention. Nine of these metabolites showed significant differences, including two metabolites increased (butyrate and citrulline), seven metabolites decreased (threonine, choline, glycine, aspartate, alanine, N-acetylglutamic acid and lysine). Pathway and enrichment analysis showed that the reduction in CVD risk by dietary intervention mainly affected five pathways, which include arginine biosynthesis; aminoacyl-tRNA biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and valine, leucine and isoleucine biosynthesis. Herein, the Guangxi longevity dietary pattern can provide a feasible healthy diet strategy for reducing the CVD risk and human beings. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR220 0058216].
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In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman's correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.