Functional metagenomic profiling of intestinal microbiome in extreme ageing

Abstract

Age-related alterations in human gut microbiota composition have been thoroughly described, but a detailed functional description of the intestinal bacterial coding capacity is still missing. In order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity, we applied shotgun sequencing to total fecal bacterial DNA in a selection of samples belonging to a well-characterized human ageing cohort. The age-related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential, while proteolytic functions were more abundant than in the intestinal metagenome of younger adults. This altered functional profile was associated with a relevant enrichment in "pathobionts", i.e. opportunistic pro-inflammatory bacteria generally present in the adult gut ecosystem in low numbers. Finally, as a signature for long life we identified 116 microbial genes that significantly correlated with ageing. Collectively, our data emphasize the relationship between intestinal bacteria and human metabolism, by detailing the modifications in the gut microbiota as a consequence of and/or promoter of the physiological changes occurring in the human host upon ageing.

References 52

1. 1.

   Weinert BT, Timiras PS. Invited review: Theories of aging. J Appl Physiol. 2003;95:1706-1716.

   Not in our library10.1152/japplphysiol.00288.2003

2. 2.

   Lovat LB. Age related changes in gut physiology and nutritional status. Gut. 1996;38:306-309.

   Not in our library10.1136/gut.38.3.306

3. 3.

   Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474:327-336.

   Not in our library10.1038/nature10213

4. 4.

   Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220-230.

   Not in our library10.1038/nature11550

5. 5.

   Faith JJ, McNulty NP, Rey FE, Gordon JI. Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science. 2011;333:101-104.

   Not in our library10.1126/science.1206025

6. 6.

   Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65-80.

   Not in our library10.1053/j.gastro.2008.10.080

7. 7.

   Biagi E, Candela M, Fairweather-Tait Tait, Franceschi C, Brigidi P. Aging of the human metaorganism: the microbial counterpart. Age. 2012;34:247-267.

   Not in our library10.1007/s11357-011-9217-5

8. 8.
   Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians · 2010

   Corrected
9. 9.

   Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz Diniz, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O'Connor M, Harnedy N, O'Connor K, Henry C, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A. 2011;1(108 Suppl):4586-4591.

   Not in our library10.1073/pnas.1000097107

10. 10.

    Bartosch S, Fite A, Macfarlane GT, McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004;70:3575-3581.

    Not in our library10.1128/aem.70.6.3575-3581.2004

11. 11.

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

    Not in our library10.1128/aem.70.10.6113-6122.2004

12. 12.

    Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T, Cresci A, Silvi S, Orpianesi C, Verdenelli MC, Clavel T, Koebnick C, Zunft HJ, Doré J, Blaut M. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006;72:1027-1033.

    Not in our library10.1128/aem.72.2.1027-1033.2006

13. 13.
    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 · 2009

    No notice
14. 14.

    Biagi E, Candela M, Turroni S, Garagnani P, Franceschi C, Brigidi P. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69:11-20.

    Not in our library10.1016/j.phrs.2012.10.005

15. 15.

    Cheng J, Palva AM, de Vos WM, Satokari R. Contribution of the intestinal microbiota to human health: from birth to 100 years of age. Curr Top Microbiol Immunol. 2013;358:323-346.

    Not in our library10.1007/82_2011_189

16. 16.

    Cevenini E, Monti D, Franceschi C. Inflamm-ageing. Curr Opin Clin Nutr Metab Care. 2013;16:14-20.

    Not in our library10.1097/mco.0b013e32835ada13

17. 17.

    Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244-254.

    Not in our library10.1111/j.1749-6632.2000.tb06651.x

18. 18.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello Bello, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222-227.

    Not in our library10.1038/nature11053

19. 19.

    Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O'Sullivan O, Fitzgerald GF, Deane J, O'Connor M, Harnedy N, O'Connor K, O'Mahony D, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178-284.

    Not in our library10.1038/nature11319

20. 20.

    Hugenholtz P, Tyson GW. Microbiology: metagenomics. Nature. 2008;455:481-483.

    Not in our library10.1038/455481a

21. 21.

    Franceschi C, Motta L, Valensin S, Rapisarda R, Franzone A, Berardelli M, Motta M, Monti D, Bonafè M, Ferrucci L, Deiana L, Pes GM, Carru C, Desole MS, Barbi C, Sartoni G, et al. Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians (IMUSCE). Aging. 2000;12:77-84.

    Not in our library10.1007/bf03339894

22. 22.
    Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism · 2013

    Corrected
23. 23.

    Gupta NK, Thaker AI, Kanuri N, Riehl TE, Rowley CW, Stenson WF, Ciorba MA. Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity. Inflamm Bowel Dis. 2012;18:1214-1220.

    Not in our library10.1002/ibd.21849

24. 24.
    Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer · 2002

    No notice
25. 25.

    Thomas DE, Chung-A-On KO, Dickerson JW, Tidmarsh SF, Shaw DM. Tryptophan and nutritional status of patients with senile dementia. Psychol Med. 1986;16:297-305.

    Not in our library10.1017/s0033291700009119

26. 26.

    Widner B, Leblhuber F, Walli J, Tilz GP, Demel U, Fuchs D. Degradation of tryptophan in neurodegenerative disorders. Adv Exp Med Biol. 1999;467:133-138.

    Not in our library10.1007/978-1-4615-4709-9_19

27. 27.

    Porter RJ, Lunn BS, Walker LL, Gray JM, Ballard CG, O'Brien JT. Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease. Am J Psychiatry. 2000;157:638-640.

    Not in our library10.1176/appi.ajp.157.4.638

28. 28.

    Noristani HN, Verkhratsky A, Rodríguez JJ. High tryptophan diet reduces CA1 intraneuronal β-amyloid in the triple transgenic mouse model of Alzheimer's disease. Aging Cell. 2012;11:810-822.

    Not in our library10.1111/j.1474-9726.2012.00845.x

29. 29.

    Smith EA, Macfarlane GT. Formation of Phenolic and Indolic Compounds by Anaerobic Bacteria in the Human Large Intestine. Microb Ecol. 1997;33:180-188.

    Not in our library10.1007/s002489900020

30. 30.

    Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242-249.

    Not in our library10.1038/nature11552

31. 31.

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

    Not in our library10.1111/j.1574-6968.2002.tb11467.x

32. 32.

    Koropatkin NM, Cameron EA, Martens EC. How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol. 2012;10:323-335.

    Not in our library10.1038/nrmicro2746

33. 33.

    Chassard C, Bernalier-Donadille A. H2 and acetate transfers during xylan fermentation between a butyrate-producing xylanolytic species and hydrogenotrophic microorganisms from the human gut. FEMS Microbiol Lett. 2006;254:116-122.

    Not in our library10.1111/j.1574-6968.2005.00016.x

34. 34.

    Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73:1073-1078.

    Not in our library10.1128/aem.02340-06

35. 35.

    Smith EA, Macfarlane GT. Dissimilatory amino Acid metabolism in human colonic bacteria. Anaerobe. 1997;3:327-337.

    Not in our library10.1006/anae.1997.0121

36. 36.

    Beck HC, Hansen AM, Lauritsen FR. Catabolism of leucine to branched-chain fatty acids in Staphylococcus xylosus. J Appl Microbiol. 2004;96:1185-1193.

    Not in our library10.1111/j.1365-2672.2004.02253.x

37. 37.

    Kaneda T. Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance. Microbiol Rev. 1991;55:288-302.

    Not in our library10.1128/mr.55.2.288-302.1991

38. 38.

    Gorąca A, Huk-Kolega Kolega, Piechota A, Kleniewska P, Ciejka E, Skibska B. Lipoic acid – biological activity and therapeutic potential. Pharmacol Rep. 2011;63:849-858.

    Not in our library10.1016/s1734-1140(11)70600-4

39. 39.

    Jones DD, Stott KM, Howard MJ, Perham RN. Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase complex of Escherichia coli. Biochemistry. 2000;39:8448-8459.

    Not in our library10.1021/bi992978i

40. 40.

    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65.

    Not in our library10.1038/nature08821

Cited by papers we hold 23

• The human gut microbiome and aging · 2024
  No notice
• Effect of metformin on sepsis-associated acute lung injury and gut microbiota in aged rats with sepsis · 2023
  Not checked
• The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases · 2023
  Corrected
• Metformin attenuated sepsis-related liver injury by modulating gut microbiota · 2022
  No notice
• Gut microbiota as the key controllers of “healthy” aging of elderly people · 2021
  No notice
• Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation · 2020
  No notice
• The Gut Microbiome, Aging, and Longevity: A Systematic Review · 2020
  No notice
• Gut microbiota and cardiovascular disease: opportunities and challenges · 2020
  No notice
• A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians · 2019
  No notice
• Precision Nutrition and the Microbiome, Part I: Current State of the Science · 2019
  No notice
• Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target · 2019
  No notice
• Counting the Countless: Bacterial Quantification by Targeting rRNA Molecules to Explore the Human Gut Microbiota in Health and Disease · 2018
  Not checked
• Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism · 2018
  No notice
• The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates · 2018
  No notice
• Changes of Colonic Bacterial Composition in Parkinson’s Disease and Other Neurodegenerative Diseases · 2018
  No notice
• (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease · 2017
  No notice
• Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut–Muscle Axis? · 2017
  No notice
• Gut microbiota changes in the extreme decades of human life: a focus on centenarians · 2017
  No notice
• Regulation of life span by the gut microbiota in the short-lived African turquoise killifish · 2017
  No notice
• Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition · 2015
  No notice

and 3 more

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.