Composition, variability, and temporal stability of the intestinal microbiota of the elderly

Proceedings of the National Academy of Sciences of the United States of America - Tập 108 Số supplement_1 - Trang 4586-4591 - 2011
Marcus J. Claesson1,2, Siobhán Cusack3, Órla O’Sullivan4, Rachel Greene-Diniz3, Heleen de Weerd5, Edel Flannery6, Julian R. Marchesi2,7, Daniel Falush8, Timothy G. Dinan1,9, Gerald F. Fitzgerald1,2, Catherine Stanton2,4, Douwe van Sinderen1,2, Michael O’Connor10,11, Norma Harnedy10,11, Kieran O’Connor12,13,14, Colm Henry13,14, Denis O’Mahony15,11,16, Anthony J. Fitzgerald17,18, Fergus Shanahan1,15, C. Twomey15,11,16, Colin Hill1,2, R. Paul Ross2,4, Paul W. O’Toole1,2
1Alimentary Pharmabiotic Centre, University College Cork, Ireland
2bAlimentary Pharmabiotic Centre, University College, Cork, Ireland;
3aDepartment of Microbiology, University College, Cork, Ireland;
4cTeagasc, Moorepark Food Research Centre, Moorepark, Fermoy, County Cork, Ireland;
5dWageningen University and Research Centre for Plant Breeding, 6708 PB, Wageningen, The Netherlands;
6eDepartment of Statistics, University College, Cork, Ireland;
7fSchool of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom;
8gEnvironmental Research Institute, University College, Cork, Ireland;
9Department of Psychiatry, University College, Cork, Ireland
10St Finbarr’s Hospital, Cork, Ireland
11iCork University Hospital, Wilton, Cork, Ireland;
12Mercy University Hospital, Cork, Ireland
13South Infirmary Victoria University Hospital, Cork, Ireland
14lSouth Infirmary, Victoria University Hospital, Cork, Ireland;
15Department of Medicine, University College, Cork, Ireland; and
16mDepartment of Medicine, University College, Cork, Ireland; and
17Department of Epidemiology and Public Health, University College Cork, Ireland
18nDepartment of Epidemiology and Public Health, University College, Cork, Ireland

Tóm tắt

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides , with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria , Actinobacteria , and Faecalibacteria . The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

Từ khóa


Tài liệu tham khảo

EG Zoetendal, M Rajilic-Stojanovic, WM de Vos, High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57, 1605–1615 (2008).

C Palmer, EM Bik, DB DiGiulio, DA Relman, PO Brown, Development of the human infant intestinal microbiota. PLoS Biol 5, e177 (2007).

PW O'Toole, MJ Claesson, Gut microbiota: Changes throughout the lifespan from infancy to elderly. Int Dairy J 20, 281–291 (2010).

L Dethlefsen, S Huse, ML Sogin, DA Relman, The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6, e280 (2008).

J Raes, KU Foerstner, P Bork, Get the most out of your metagenome: Computational analysis of environmental sequence data. Curr Opin Microbiol 10, 490–498 (2007).

CF Favier, EE Vaughan, WM De Vos, AD Akkermans, Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol 68, 219–226 (2002).

EG Zoetendal, AD Akkermans, WM De Vos, Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl Environ Microbiol 64, 3854–3859 (1998).

J Tap, et al., Towards the human intestinal microbiota phylogenetic core. Environ Microbiol 11, 2574–2584 (2009).

M Rajilić-Stojanović, H Smidt, WM de Vos, Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol 9, 2125–2136 (2007).

PJ Turnbaugh, et al., An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

DN Frank, et al., Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104, 13780–13785 (2007).

A Kassinen, et al., The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133, 24–33 (2007).

PJ Turnbaugh, et al., A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

SH Duncan, et al., Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond) 32, 1720–1724 (2008).

A Schwiertz, et al., Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190–195 (2010).

PJ Turnbaugh, et al., The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1, 6–14 (2009).

P Louis, HJ Flint, Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 294, 1–8 (2009).

SE Pryde, SH Duncan, GL Hold, CS Stewart, HJ Flint, The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett 217, 133–139 (2002).

C Manichanh, et al., Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205–211 (2006).

M Martinez-Medina, X Aldeguer, F Gonzalez-Huix, D Acero, LJ Garcia-Gil, Abnormal microbiota composition in the ileocolonic mucosa of Crohn's disease patients as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. Inflamm Bowel Dis 12, 1136–1145 (2006).

H Sokol, et al., Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105, 16731–16736 (2008).

A Darfeuille-Michaud, et al., High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127, 412–421 (2004).

R Kotlowski, CN Bernstein, S Sepehri, DO Krause, High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut 56, 669–675 (2007).

K Kinsella, W He US Census Bureau. An Aging World: 2008 (International Population Reports, Washington, DC, 2009).

B Kleessen, B Sykura, HJ Zunft, M Blaut, Effects of inulin and lactose on fecal microflora, microbial activity, and bowel habit in elderly constipated persons. Am J Clin Nutr 65, 1397–1402 (1997).

M Camilleri, JS Lee, B Viramontes, AE Bharucha, EG Tangalos, Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people. J Am Geriatr Soc 48, 1142–1150 (2000).

C Franceschi, et al., Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908, 244–254 (2000).

A Salminen, et al., Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 7, 83–105 (2008).

T Mitsuoka Intestinal Bacteria and Health (Harcourt Brace Jovanovich, Tokyo, 1978).

MJ Hopkins, GT Macfarlane, Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol 51, 448–454 (2002).

EJ Woodmansey, Intestinal bacteria and ageing. J Appl Microbiol 102, 1178–1186 (2007).

EJ Woodmansey, ME McMurdo, GT Macfarlane, S Macfarlane, Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects. Appl Environ Microbiol 70, 6113–6122 (2004).

H Hayashi, M Sakamoto, M Kitahara, Y Benno, Molecular analysis of fecal microbiota in elderly individuals using 16S rDNA library and T-RFLP. Microbiol Immunol 47, 557–570 (2003).

S Mueller, et al., Differences in fecal microbiota in different European study populations in relation to age, gender, and country: A cross-sectional study. Appl Environ Microbiol 72, 1027–1033 (2006).

MJ Claesson, et al., Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine. PLoS ONE 4, e6669 (2009).

JR Cole, et al., The Ribosomal Database Project: Improved alignments and new tools for rRNA analysis. Nucleic Acids Res 37, D141–D145 (2009).

MD Collins, et al., The phylogeny of the genus Clostridium: Proposal of five new genera and eleven new species combinations. Int J Syst Bacteriol 44, 812–826 (1994).

H Sokol, et al., Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis 12, 106–111 (2006).

H Sokol, et al., Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15, 1183–1189 (2009).

M Li, et al., Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci USA 105, 2117–2122 (2008).

H Zhang, et al., Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA 106, 2365–2370 (2009).

M Rajilić-Stojanović, et al., Development and application of the human intestinal tract chip, a phylogenetic microarray: Analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol 11, 1736–1751 (2009).

MF De La Cochetière, et al., Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol 43, 5588–5592 (2005).

AF Andersson, et al., Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS ONE 3, e2836 (2008).

PB Eckburg, et al., Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

SR Gill, et al., Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

M Ventura, et al., Genome-scale analyses of health-promoting bacteria: Probiogenomics. Nat Rev Microbiol 7, 61–71 (2009).

J Zwielehner, et al., Combined PCR-DGGE fingerprinting and quantitative-PCR indicates shifts in fecal population sizes and diversity of Bacteroides, bifidobacteria and Clostridium cluster IV in institutionalized elderly. Exp Gerontol 44, 440–446 (2009).

MN Price, PS Dehal, AP Arkin, FastTree: Computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 26, 1641–1650 (2009).

M Hamady, C Lozupone, R Knight, Fast UniFrac: Facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J 4, 17–27 (2010).

DH Huson, et al., Dendroscope: An interactive viewer for large phylogenetic trees. BMC Bioinformatics, 10.1186/1471-2105-8-460. (2007).

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 108 Số supplement_1

4586-4591

Thông tin tác giả