Kim, Bong-Soo
(Department of Life Science, Hallym University)
,
Choi, Chong Won
(Department of Dermatology, Seoul National University College of Medicine)
,
Shin, Hyoseung
(Department of Dermatology, Seoul National University College of Medicine)
,
Jin, Seon-Pil
(Department of Dermatology, Seoul National University College of Medicine)
,
Bae, Jung-Soo
(Department of Dermatology, Seoul National University College of Medicine)
,
Han, Mira
(Department of Dermatology, Seoul National University College of Medicine)
,
Seo, Eun Young
(Department of Dermatology, Seoul National University College of Medicine)
,
Chun, Jongsik
(School of Biological Sciences and Inst. of Molecular Biology and Genetics, Seoul National University)
,
Chung, Jin Ho
(Department of Dermatology, Seoul National University College of Medicine)
Several studies have attempted to identify factors associated with longevity and maintenance of health in centenarians. In this study, we analyzed and compared the gut microbiota of centenarians in longevity villages with the elderly and adults in the same region and urbanized towns. Fecal samples w...
Several studies have attempted to identify factors associated with longevity and maintenance of health in centenarians. In this study, we analyzed and compared the gut microbiota of centenarians in longevity villages with the elderly and adults in the same region and urbanized towns. Fecal samples were collected from centenarians, elderly, and young adults in longevity villages, and the gut microbiota sequences of elderly and young adults in urbanized towns of Korea were obtained from public databases. The relative abundance of Firmicutes was found to be considerably higher in subjects from longevity villages than those from urbanized towns, whereas Bacteroidetes was lower. Age-related rearrangement of gut microbiota was observed in centenarians, such as reduced proportions of Faecalibacterium and Prevotella, and increased proportion of Escherichia, along with higher abundances of Akkermansia, Clostridium, Collinsella, and uncultured Christensenellaceae. Gut microbiota of centenarians in rehabilitation hospitals were also different to those residing at home. These differences could be due to differences in diet patterns and living environments. In addition, phosphatidylinositol signaling system, glycosphingolipid biosynthesis, and various types of N-glycan biosynthesis were predicted to be higher in the gut microbiota of centenarians (corrected p < 0.05). These three metabolic pathways of gut microbiota can be associated with the immune status and healthy gut environment of centenarians. Although further studies are necessary to validate the function of microbiota between groups, this study provides valuable information on centenarians' gut microbiota.
Several studies have attempted to identify factors associated with longevity and maintenance of health in centenarians. In this study, we analyzed and compared the gut microbiota of centenarians in longevity villages with the elderly and adults in the same region and urbanized towns. Fecal samples were collected from centenarians, elderly, and young adults in longevity villages, and the gut microbiota sequences of elderly and young adults in urbanized towns of Korea were obtained from public databases. The relative abundance of Firmicutes was found to be considerably higher in subjects from longevity villages than those from urbanized towns, whereas Bacteroidetes was lower. Age-related rearrangement of gut microbiota was observed in centenarians, such as reduced proportions of Faecalibacterium and Prevotella, and increased proportion of Escherichia, along with higher abundances of Akkermansia, Clostridium, Collinsella, and uncultured Christensenellaceae. Gut microbiota of centenarians in rehabilitation hospitals were also different to those residing at home. These differences could be due to differences in diet patterns and living environments. In addition, phosphatidylinositol signaling system, glycosphingolipid biosynthesis, and various types of N-glycan biosynthesis were predicted to be higher in the gut microbiota of centenarians (corrected p < 0.05). These three metabolic pathways of gut microbiota can be associated with the immune status and healthy gut environment of centenarians. Although further studies are necessary to validate the function of microbiota between groups, this study provides valuable information on centenarians' gut microbiota.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
문제 정의
Further studies are needed to validate the function of the gut microbiota of the centenarians and the influences of diet in longevity villages on the formation of the gut microbiota in centenarians. This study provides information on the gut microbiota of centenarians and helps to identify characteristics of gut microbiota that enable healthy aging in human beings.
Therefore, in this study, we analyzed the gut microbiota of centenarians living in these four regions and compared the results to those of healthy elderly individuals and adults in the same regions and urbanized towns. This study will provide comprehensive information of the gut microbiota of centenarians in longevity villages and help to characterize the role of gut microbiota in healthy aging.
가설 설정
(C) The average composition of gut microbiota obtained from two groups. (D) Frequently detected genera were compared between groups. The significance of the differences between groups was tested using the Mann-Whitney test.
제안 방법
In addition, subjects who had used systemic antibiotics within one month were also excluded. A written consent form and completed questionnaire regarding the age, gender, past medical history, use of antibiotics, and characteristics of diet were obtained from each of the subjects. The study protocol was approved by the Ethical Community of Seoul National University Hospital (IRB No: H-1210-091-435).
The dietary data of the subjects were collected through a food frequency questionnaire including the status of appetite, the numbers of meals and snacks per day, and the consumption frequency of each food group per month (Table 1). The number of meals and snacks was higher among centenarians and the elderly group compared with that of the adult group (p < 0.
3). The difference in gut microbiota between centenarians from rehabilitation hospitals and community-dwelling subjects was analyzed. The diversity indices (observed OTUs and Shannon diversity) of the community-dwelling centenarians were higher than that of the centenarians in rehabilitation hospitals (Figs.
The gut microbiome might be one of the important factors in the prevalence of centenarians in these regions. Therefore, in this study, we analyzed the gut microbiota of centenarians living in these four regions and compared the results to those of healthy elderly individuals and adults in the same regions and urbanized towns. This study will provide comprehensive information of the gut microbiota of centenarians in longevity villages and help to characterize the role of gut microbiota in healthy aging.
대상 데이터
0) [33]. All raw sequence reads obtained in this study are available in the EMBL SRA database under study number PRJEB7507 (http://www.ebi.ac.uk/ena/data/view/PRJEB7507).
Thirty centenarians (aged 95 to 108 years; average 98.9 ± 3.4), 17 elderly (aged 67 to 79 years; average 73.6 ± 3.6), and 9 adults (aged 26 to 43 years; average 34.3 ± 6.5) in longevity villages were enrolled in this study.
데이터처리
Clustering analysis was conducted using the Spearman rank correlation. Yellow green indicates centenarians, blue indicates the elderly, red indicates adults, yellow indicates community-dwelling (CD), and gray indicates rehabilitation hospital (RH).
The differences of bacterial taxa among groups were tested by Kruskal-Wallis rank-sum test in R software. Mann-Whitney U-test was performed to identify statistically significant pairwise differences between the groups. Significantly different predicted KEGG pathways were determined using the Kruskal-Wal l is H-test, and a post-hoc test was performed using the Tukey-Kramer method [34].
The differences of bacterial taxa among groups were tested by Kruskal-Wallis rank-sum test in R software. Mann-Whitney U-test was performed to identify statistically significant pairwise differences between the groups.
The decreased proportions of Faecalibacterium and Prevotella were also detected in subjects of urbanized towns according to aging. The heatmap analysis of genera was used to compare the gut microbiota among centenarians, the elderly, and adults in longevity villages using the Spearman rank correlation (Fig. 3). Although the microbiota of centenarians, the elderly, and adults were not separated clearly, microbiota of centenarians in rehabilitation hospitals were clustered together, apart from those of communitydwelling centenarians.
이론/모형
Sequences were separated by unique barcodes, and low-quality reads (average quality score < 25 or read length < 300 bp) and primer sequences were removed using USEARCH program [26]. Chimeric sequences were removed using the UPARSE tool [27]. Sequences were clustered into operational taxonomic units (OTUs) at 97% similarity, and representative sequences in each cluster were identified using RDP classifier [28] with the EzTaxon-e database [29].
Mann-Whitney U-test was performed to identify statistically significant pairwise differences between the groups. Significantly different predicted KEGG pathways were determined using the Kruskal-Wal l is H-test, and a post-hoc test was performed using the Tukey-Kramer method [34]. The multiple test corrections were made using Benjamini-Hochberg False Discovery Rate.
The LEfSe (linear discriminant analysis coupled with effect size measurements) was used to find potential markers among different groups [32]. The functional prediction of microbiota was performed using the PICRUSt (ver. 1.0.0) [33]. All raw sequence reads obtained in this study are available in the EMBL SRA database under study number PRJEB7507 (http://www.
Significantly different predicted KEGG pathways were determined using the Kruskal-Wal l is H-test, and a post-hoc test was performed using the Tukey-Kramer method [34]. The multiple test corrections were made using Benjamini-Hochberg False Discovery Rate. Results with p value< 0.
Sequences were clustered into operational taxonomic units (OTUs) at 97% similarity, and representative sequences in each cluster were identified using RDP classifier [28] with the EzTaxon-e database [29]. The read numbers in each sample were normalized by random sampling, and the diversity indices were calculated using the Mothur program [30]. Principal coordinate analysis (PCoA) was performed to compare the microbiota among groups, based on the Bray-Curtis distance using Calypso [31].
5% of all subjects were selected and compared. The significance of the differences between groups was tested using the Mann-Whitney test. L_C, centenarians in longevity villages; L_E, elderly in longevity villages; L_A, adults in longevity villages; U_E, elderly in urbanized town; U_A, adults in urbanized town.
The proportion of environmental information processing was higher in the gut microbiomes of centenarians and the elderly than that in adults. The significantly different metabolic pathway was selected using Kruskal-Wallis H-test with Benjamini-Hochberg correction (Table S4). A total of 26 categories were selected by corrected p value < 0.
Two metabolic pathways were selected by KruskalWallis H-test with Benjamini-Hochberg correction (p < 0.1) (Table S5).
성능/효과
In conclusion, we identified the different members of gut microbiota in centenarians compared with those in the elderly and adults in longevity villages and urbanized towns. The dietary characteristics of the centenarians in longevity villages showed that the centenarians had regular dietary habits with diverse food intake.
5C). The proportions of Firmicutes (67.0%) and Tenericutes (3.0%) were higher in gut microbiota of community-dwelling subjects than those (61.2% and 1.1%) in rehabilitation hospitals, whereas Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia were higher in the centenarians in rehabilitation hospitals. The significantly different genera between community-dwelling subjects and rehabilitation hospital subjects were detected (Fig.
004). The questionnaire about the status of appetite also showed no differences between the groups as (72.0% (18/25) of centenarians, 53.8% (7/13) of elderly, and 77.8% (7/9) of adults had good appetite, p = 0.411). The frequencies of intake of each food group (meat, eggs, fish, bean curd, fermented soybean pastes, dairy products, and fruits) were compared and it was found that adults (17.
S2). The relative abundances of Faecalibacterium and Prevotella were lower in centenarians compared with other groups, and Escherichia within Proteobacteria was increased along with aging (Fig. 2). This result was similar to the age-related rearrangement of gut microbiota in previous studies [12, 14, 15, 17, 18].
The relative abundances of Proteobacteria (8.05%), Actinobacteria (2.17%), and Verrucomicrobia (2.52%) were significantly higher in centenarians than those of adults (0.06% with p < 0.001, 0.61% with p < 0.05, and 0.00% with p < 0.01, respectively).
후속연구
These functions of gut microbiota can be related to the healthy gut environment of centenarians. Further studies are needed to validate the function of the gut microbiota of the centenarians and the influences of diet in longevity villages on the formation of the gut microbiota in centenarians. This study provides information on the gut microbiota of centenarians and helps to identify characteristics of gut microbiota that enable healthy aging in human beings.
참고문헌 (57)
Willcox DC, Willcox BJ, He Q, Wang NC, Suzuki M. 2008. They really are that old: a validation study of centenarian prevalence in Okinawa. J. Gerontol. A, Biol. Sci. Med. Sci. 63: 338-349.
Smith DW. 1997. Centenarians: human longevity outliers. Gerontologist 37: 200-206.
Bernstein AM, Willcox BJ, Tamaki H, Kunishima N, Suzuki M, Willcox DC, et al. 2004. First autopsy study of an Okinawan centenarian: absence of many age-related diseases. J. Gerontol. A, Biol. Sci. Med. Sci. 59: 1195-1199.
Evert J, Lawler E, Bogan H, Perls T. 2003. Morbidity profiles of centenarians: survivors, delayers, and escapers. J. Gerontol. A, Biol. Sci. Med. Sci. 58: 232-237.
Franceschi C, Passarino G, Mari D, Monti D. 2017. Centenarians as a 21st century healthy aging model: A legacy of humanity and the need for a world-wide consortium (WWC100+). Mech. Ageing Dev. 165: 55-58.
Kheirbek RE, Fokar A, Shara N, Bell-Wilson LK, Moore HJ, Olsen E, et al. 2017. Characteristics and incidence of chronic illness in community-dwelling predominantly male U.S. Veteran centenarians. J. Am. Geriatr. Soc. 65: 2100-2106.
Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. 2012. Human gut microbiome viewed across age and geography. Nature 486: 222-227.
Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. 2009. Human gut microbiota in obesity and after gastric bypass. Proc. Natl. Acad. Sci. USA 106: 2365-2370.
Wu GD, Lewis JD. 2013. Analysis of the human gut microbiome and association with disease. Clin. Gastroenterol. Hepatol. 11: 774-777.
Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, Cusack S, et al. 2012. Gut microbiota composition correlates with diet and health in the elderly. Nature 488: 178-184.
Candela M, Biagi E, Brigidi P, O'Toole PW, De Vos WM. 2014. Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach. Mech. Ageing Dev. 136-137: 70-75.
Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, et al. 2010. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One 5: e106967.
Wang F, Yu T, Huang G, Cai D, Liang X, Su H, et al. 2015. Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. J. Microbiol. Biotechnol. 25: 1195-1204.
Park SH, Kim KA, Ahn YT, Jeong JJ, Huh CS, Kim DH. 2015. Comparative analysis of gut microbiota in elderly people of urbanized towns and longevity villages. BMC Microbiol. 15: 49.
Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, et al. 2016. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 16: 90.
Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, et al. 2016. Gut microbiota and extreme longevity. Curr. Biol. 26: 1480-1485.
Guigoz Y, Dore J, Schiffrin EJ. 2008. The inflammatory status of old age can be nurtured from the intestinal environment. Curr. Opin. Clin. Nutr. Metab. Care 11: 13-20.
Woodmansey EJ. 2007. Intestinal bacteria and ageing. J. Appl. Microbiol. 102: 1178-1186.
Buford TW. 2017. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome 5: 80.
Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, et al. 2018. Gut microbiota changes in the extreme decades of human l ife: a focus on centenarians. Cell Mol. Life Sci. 75: 129-148.
Hur M, Kim Y, Song HR, Kim JM, Choi YI, Yi H. 2011. Effect of genetically modified poplars on soil microbial communities during the phytoremediation of waste mine tailings. Appl. Environ. Microbiol. 77: 7611-7619.
Jeon YS, Chun J, Kim BS. 2013. Identification of household bacterial community and analysis of species shared with human microbiome. Curr. Microbiol. 67: 557-563.
Kim BS, Bae HS, Lim CY, Kim MJ, Seo JG, Kim JY, et al. 2013. Comparison of gut microbiota between sasang constitutions. Evid. Based Complement. Alternat. Med. 2013: 171643.
Werner JJ, Koren O, Hugenholtz P, DeSantis TZ, Walters WA, Caporaso JG, et al. 2012. Impact of training sets on classification of high-throughput bacterial 16S rRNA gene surveys. ISME J. 6: 94-103.
Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, et al. 2017. Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int. J. Syst. Evol. Microbiol. 67: 1613-1617.
Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, et al. 2009. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75: 7537-7541.
Zakrzewski M, Proietti C, Ellis JJ, Hasan S, Brion MJ, Berger B, et al. 2017. Calypso: a user-friendly web-server for mining and visualizing microbiome-environment interactions. Bioinformatics 33: 782-783.
Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. 2011. Metagenomic biomarker discovery and explanation. Genome Biol. 12: R60.
Lee M. 2005. The dietary habits of the nonagenarian population in longevity belt in Korea. Korean J. Community Nutr. 10: 513-524.
Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, et al. 2015. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528: 262-266.
Gerritsen J, Hornung B, Renckens B, van Hijum S, Martins Dos Santos VAP, Rijkers GT, et al. 2017. Genomic and functional analysis of Romboutsia ilealis CRIB(T) reveal sadaptation to the small intestine. PeerJ. 5: e3698.
Zhong Y, Nyman M, Fak F. 2015. Modulation of gut microbiota in rats fed high-fat diets by processing wholegrain barley to barley malt. Mol. Nutr. Food Res. 59: 2066-2076.
Rode LM, Genthner BR, Bryant MP. 1981. Syntrophic association by cocultures of the methanol-and $CO_2-H_2$ -utilizing species Eubacterium limosum and pectin-fermenting Lachnospira multiparus during growth in a pectin medium. Appl. Environ. Microbiol. 42: 20-22.
Marounek M, Duskova D. 1999. Metabolism of pectin in rumen bacteria Butyrivibrio fibrisolvens and Prevotella ruminicola. Lett. Appl. Microbiol. 29: 429-433.
Lim MY, Rho M, Song YM, Lee K, Sung J, Ko G. 2014. Stability of gut enterotypes in Korean monozygotic twins and their association with biomarkers and diet. Sci. Rep. 4: 7348.
Hobbs ME, Williams HJ, Hillerich B, Almo SC, Raushel FM. 2014. l-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53: 4661-4670.
Renouf M, Hendrich S. 2011. Bacteroides uniformis is a putative bacterial species associated with the degradation of the isoflavone genistein in human feces. J. Nutr. 141: 1120-1126.
Cevenini E, Monti D, Franceschi C. 2013. Inflamm-ageing. Curr. Opin. Clin. Nutr. Metab. Care 16: 14-20.
De Martinis M, Franceschi C, Monti D, Ginaldi L. 2005. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett. 579: 2035-2039.
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. 2007. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128: 92-105.
Jeong JJ, Kim KA, Hwang YJ, Han MJ, Kim DH. 2016. Antiinflammaging effects of Lactobacillus brevis OW38 in aged mice. Benef. Microbes 7: 707-718.
Drago L, Toscano M, Rodighiero V, De Vecchi E, Mogna G. 2012. Cultivable and pyrosequenced fecal microflora in centenarians and young subjects. J. Clin. Gastroenterol. 46 (Suppl): S81-84.
Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A. 2013. Commensal Clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog. 5: 23.
Gomez-Arango LF, Barrett HL, Wilkinson SA, Callaway LK, McIntyre HD, Morrison M, et al. 2017. Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women. Gut Microbes 9: 189-201.
Angelakis E, Yasir M, Bachar D, Azhar EI, Lagier JC, Bibi F, et al. 2016. Gut microbiome and dietary patterns in different Saudi populations and monkeys. Sci. Rep. 6: 32191.
Thakur PC, Davison JM, Stuckenholz C, Lu L, Bahary N. 2014. Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress-mediated intestinal mucosal injury and inflammation in zebrafish. Dis. Model Mech. 7: 93-106.
Bourassa MW, Alim I, Bultman SJ, Ratan RR. 2016. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? Neurosci. Lett. 625: 56-63.
An D, Oh SF, Olszak T, Neves JF, Avci FY, Erturk-Hasdemir D, et al. 2014. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156: 123-133.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.