| Longevity and healthy are the eternal theme of human beings,human life expectancy increases year by year,however,the extra years of life is not always equal to healthy life years,older population likely to suffer from many chronic diseases such as diabetes,hypertension,high cholesterol,cardiovascular disease,cognitive decline,which influence the quality of the elderly in later life.Studies show that diet is considered to be the most important factor affecting healthy and longevity.Diet can change the structure of intestinal flora of host,regulate the metabolic function of host,and thus affect the health of host.Adjusting dietary factors to change intestinal microbial structure and its metabolites may be a convenient,economic and effective means to prevent and treat chronic diseases and improve the health of the elderly.Hechi region of Guangxi,China is famous for its high proportion of long-lived population,and most of the local long-lived elderly are healthy and live a long life.In this study,healthy people from longevity families in Hechi region of Guangxi were selected as the research objects.Starting from the dietary survey,the intestinal microflora structure and metabolic characteristics related to diet were explored,and the dietary,intestinal microflora and metabolite factors related to longevity were explored.Further experiments on volunteers’ diet intervention and animal model intervention were carried out to verify the anti-aging effect and explore the mechanism of anti-aging.The main contents,methods and conclusions of the study are as follows:(1)The gut microbiota structure of subjects from longevity families in Hechi region was analyzed by high-throughput sequencing,and the structural characteristics of gut microbiota related to longevity were explored.It was found that the gut microbiota of the long-lived elderly had higher species diversity than that of their young offspring.The core microbiota of different age groups in longevity families were dominated by Ruminococcaceae,Lachnospiraceae,Enterobacteraceae and Bacteroidaceae.The accumulative abundance remained stable between groups.But the structure of the core microbiota had profound changes,for example,the relative abundance of Oscillospira in Ruminococcaceae was significantly higher in the long-lived elderly group than that in the offspring group.However,Butyricicoccus and Faecalibacterium in Ruminococcaceae were significantly lower in the long-lived elderly group than those in the offspring group.The relative abundance of Lachnospiraceae,Prevotellaceae,Roseburia,Blautia and Prevotella were dramatically decreased with age.Based on the functional prediction of gut microbiota,the proportion of gene associated with short chain fatty acid metabolic and amino acid metabolic pathways were significantly higher than younger descendants.(2)The gut microbiota compositions of healthy middle-aged and elderly people from longevity area and non-longevity area(control group)were compared.Compared with the control group,the relative abundance of Lachnospiraceae,Roseburia,Ruminococcus,and Lactobacillus in longevity families were significantly increased,but the abundance of Bacteroidaceae was significantly decreased.(3)The diet information of the long-lived population and the control group was evaluated.It was found that the intake of whole grains and tuberous crops in the long-lived family group was significantly higher than that in the control group.At the nutrient level,the intake of dietary fibers and carbohydrate in the long-lived family group was significantly greater than that in the control group.Spearman correlation analysis between diet and gut microbiota showed that dietary fibers and carbohydrate intake were dramatically positively correlated with the abundances of Lachnospiraceae,Prevotellaceae,Roseburia,Lachnospira,Faecalibacterium and Prevotella.The intake of protein and fat was significantly positively correlated with Bacteroidaceae,Porphyromonadaceae,Bacteroides and Parabacteroides.The intake of vegetables and fruits was significantly positively correlated with Christensenellaceae and Oscillospira.(4)The fecal metabolites of the long-lived population and the control group were detected.Multivariate statistical analysis was used to excavate the characteristic metabolites associated with longevity,and the correlation between characteristic metabolites and intestinal microbes was analyzed.It was found that six metabolites(including acetic acid,etc.)in the feces of the long-lived elderly group were significantly down-regulated compared with the young offspring group,while eleven metabolites(including isoleucine,etc.)were significantly up-regulated.Compared with the control group,the fecal metabolites of SCFAs were significantly up-regulated in offspring group of long-lived ederly.Spearman correlation analysis showed that the abundance olf Lachnospiraceae,Roseburia,Lachnospira,Faecalibacterium were significantly positive related with acetic acid,butyric acid and valeric acid;Prevotellaceae and Prevotella were positively correlated with propionic acid and isobutyric acid.Christensenellaceae,Oscillospira,Eubacterium have significant positive correlation with alanine,glutamic acid,phenylalanine,leucine,methionine,isoleucine,etc.(5)The effects of special dietary fiber intake and probiotic mix supplementation dietary intervention on blood parameters and gut microbiota in elderly volunteers were studied using whole foods supply dietary intervention.Probiotics combined with a high-fiber diet were found to improve health-related parameters,such as reduced serum cholesterol and triglycerides,and significantly reduced fasting blood glucose in elderly.After dietary intervention,the fecal abundance of Lachnospiraceae,Lachnospiracea＿incertae＿sedis and Lactobacillus were significantly increased in the sub-healthy elderly.The abundance of Bacteroides,Prevotella and Faecalibacterium increased in feces of healthy elderly.After dietary intervention,the content of SCFAs in feces of the elderly was significantly increased.Correlation analysis showed that SCFAs was significantly correlated with fasting blood glucose,body weight,body mass index creatinine,uric acid and other health indicators.(6)In this study,the effefts of a special dietary fiber complex derived from the diet of the long-lived population combined with three strains of centenarian source lactobacillus(including L.casei LTL1361,L.fermentum LTP1332 and L.reuteri LTR1318 on the cognitive ability,antioxidant capacity and inflammation in aging mice were investigated.A common commercial L.casei strain was used as positive control.Three strains of lactobacillus combined with dietary fiber complex significantly improved the performance of aging mice in the water maze test,significantly reduced the escape latency,and enhanced the number of platform crossing and the time spend in the target quadrant.L.casei LTL1361,L.fermentum LTP1332 and L.reuteri LTR1318 combined with dietary fiber complex decreased the levels of oxidative stress and inflammation in serum of aging mice by significantly increased the serum total antioxidant capacity,SOD activity and IL-10 concentration,and decreased the concentrations of MDA and TNF-α.There were no significant differences between the combined probiotics group and the single probiotics group,and the anti-oxidation effect of L.casei LTL1361 was significantly better than control strains.The intervention with the combination of probiotics and dietary fibers increased the content of SCFAs,especially butyric acid.Correlation analysis showed that butyric acid and acetic acid concentrations were significantly positively correlated with serum total antioxidant capacity and IL-10,and significantly negatively correlated with pro-inflammatory marker TNF-α.(7)The effects of L.casei LTL1361 or dietary fiber complex and their combination on the cognitive ability of naturally aging mice were investigated,and the hippocampal cell morphology,antioxidant level and aging-related gene expression in the brain were investigated to explore the related mechanism.L.casei LTL1361 and dietary fiber complex significantly improved spatial learning and memory in aged mice,and the effect was significantly better with the combination of L.casei LTL1361 and dietary fiber complex.L.casei LTL1361 and dietary fiber complex improved the morphology of pyramidal nerve cells in hippocampal CA1 region in the brain of aged mice,significantly improved the antioxidant capacity.The m RNA expressions of pro-apoptotic factors caspase-3and Bax were down-regulated,and the gene expression of anti-apoptotic protein Bcl-2 was up-regulated.The relative expression levels of amyloid precursor(APP),presenin 1(PS1)and p53 genes in mouse brain tissues were significantly down-regulated,and the relative expression levels of SIRT1 gene,an anti-aging gene,were significantly up-regulated.(8)L.casei LTL1361 and dietary fiber complex improved intestinal barrier function by regulating gut microbiota structure,increasing SCFAs contents,and down-regulating inflammatory level.L.casei LTL1361 and dietary fiber complex improve intestinal cell morphology,decreased the concentration of pro-inflammatory cytokines TNF-α and increased the concentration of anti-inflammatory cytokines IL-10.The relative m RNA expression of p38 and JNK in MAPK inflammatory signaling pathway were significantly down-regulated.The intestinal barrier function of aging mice was improved by significantly increasing the relative expression levels of claudin-1,ZO-1 and Muc1 genes in small intestine and colon tissues.It significantly increased the content of SCFAs in feces and the relative expression levels of SCFAs receptor proteins GPR41 and GPR43 in tissues.Dietary fiber complex up-regulated the relative abundance of SCFAs producing bacteria Roseburia and Faecalibacterium,while L.casei LTL1361 up-regulated the abundance of Lactobacillus and Ruminococcus.In conclusion,the high dietary fibers intake of the long-lived population in Hechi region of Guangxi was related to the high abundance of SCFAs producing bacteria in gut microbiota and the high SCFAs content in feces.The special dietary fibers derived from the diet characteristics of long-lived people and centenarian-sourced probiotics can improve the health indicators and intestinal microflora structure of elderly volunteers,and improve the intestinal barrier function and cognitive ability of naturally aging mice,and reduce the levels of oxidative stress and inflammation.This explains the mechanism of anti-aging effect of the special dietary fiber complex derived from longevity and centenarian-sourced lactobacillus strain in different aspects. |
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