Role of gut microbiota in aging-related health decline: insights from invertebrate models

Cellular and Molecular Life Sciences

Volumn 75, Issue 1, 2018, Pages 93-101

  Clark, Rebecca I ^a   Walker, David W ^b  

^a DURHAM UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Dysbiosis; Intestinal barrier; Longevity; Microbiome; Mortality

Indexed keywords

AGING; HEALTH; HOST; INTESTINE FLORA; INVERTEBRATE MODEL; LIFESPAN; LONGEVITY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; ANIMAL; ANIMAL MODEL; CAENORHABDITIS ELEGANS; DROSOPHILA; HUMAN; INTESTINE; MICROBIOLOGY; PHYSIOLOGY;

AGING; ANIMALS; CAENORHABDITIS ELEGANS; DROSOPHILA; GASTROINTESTINAL MICROBIOME; HUMANS; INTESTINES; LONGEVITY; MODELS, ANIMAL;

EID: 85031407611     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-017-2671-1     Document Type: Review

References (92)

1. Gems D, Partridge L (2013) Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol 75:621–644. doi:10.1146/annurev-physiol-030212-183712
2. Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512. doi:10.1038/nature08980
3. Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, Curiel TJ, de Cabo R, Franceschi C, Gems D, Ingram DK, Johnson TE, Kennedy BK, Kenyon C, Klein S, Kopchick JJ, Lepperdinger G, Madeo F, Mirisola MG, Mitchell JR, Passarino G, Rudolph KL, Sedivy JM, Shadel GS, Sinclair DA, Spindler SR, Suh Y, Vijg J, Vinciguerra M, Fontana L (2015) Interventions to slow aging in humans: are we ready? Aging Cell 14(4):497–510. doi:10.1111/acel.12338
4. Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350(6265):1191–1193. doi:10.1126/science.aad3267
5. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328(5976):321–326. doi:10.1126/science.1172539
6. Libina N, Berman JR, Kenyon C (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115(4):489–502
7. Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144(1):79–91. doi:10.1016/j.cell.2010.12.016
8. Biteau B, Karpac J, Supoyo S, Degennaro M, Lehmann R, Jasper H (2010) Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet 6(10):e1001159. doi:10.1371/journal.pgen.1001159
9. Guo L, Karpac J, Tran SL, Jasper H (2014) PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 156(1–2):109–122. doi:10.1016/j.cell.2013.12.018
10. Hur JH, Bahadorani S, Graniel J, Koehler CL, Ulgherait M, Rera M, Jones DL, Walker DW (2013) Increased longevity mediated by yeast NDI1 expression in Drosophila intestinal stem and progenitor cells. Aging (Albany NY) 5(9):662–681
11. Rera M, Azizi MJ, Walker DW (2013) Organ-specific mediation of lifespan extension: more than a gut feeling? Ageing Res Rev 12(1):436–444. doi:10.1016/j.arr.2012.05.003
12. Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M, Hur JH, Ansari WS, Lo T Jr, Jones DL, Walker DW (2011) Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab 14(5):623–634. doi:10.1016/j.cmet.2011.09.013
13. Ulgherait M, Rana A, Rera M, Graniel J, Walker DW (2014) AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep 8(6):1767–1780. doi:10.1016/j.celrep.2014.08.006
14. Li H, Qi Y, Jasper H (2016) Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan. Cell Host Microbe 19(2):240–253. doi:10.1016/j.chom.2016.01.008
15. Jasper H (2015) Exploring the physiology and pathology of aging in the intestine of Drosophila melanogaster. Invertebr Reprod Dev 59(sup1):51–58. doi:10.1080/07924259.2014.963713
16. Zoetendal EG, Akkermans ADL, De Vos WM (1998) 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(10):3854–3859
17. Rajilić-Stojanović M, Heilig HGHJ, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM (2009) 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(7):1736–1751. doi:10.1111/j.1462-2920.2009.01900.x
18. Curtis M (2016) An introduction to microbial dysbiosis. In: Henderson B, Nibali L (eds) The human microbiota and chronic disease. Dysbiosis as a cause of human pathology. Wiley, Blackwell Publishing (Holdings) Ltd, Hoboken, New Jersey, United States
19. Clemente JC, Ursell LK, Parfrey LW, Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148(6):1258–1270. doi:10.1016/j.cell.2012.01.035
20. O’Toole PW, Jeffery IB (2015) Gut microbiota and aging. Science 350(6265):1214–1215. doi:10.1126/science.aac8469
21. Belizário JE, Napolitano M (2015) Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol. doi:10.3389/fmicb.2015.01050
22. Consortium TIHiRN (2014) The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16(3):276–289. doi:10.1016/j.chom.2014.08.014
23. McGhee JD (2007) The C. elegans intestine. In: Community TCer (ed) WormBook. doi:10.1895/wormbook.1.133.1
24. Buchon N, Osman D, David FP, Fang HY, Boquete JP, Deplancke B, Lemaitre B (2013) Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep 3(5):1725–1738. doi:10.1016/j.celrep.2013.04.001
25. Lemaitre B, Miguel-Aliaga I (2013) The digestive tract of Drosophila melanogaster. Annu Rev Genet 47:377–404. doi:10.1146/annurev-genet-111212-133343
26. Tissenbaum HA (2015) Using C. elegans for aging research. Invertebr Reprod Dev 59(sup1):59–63. doi:10.1080/07924259.2014.940470
27. Melov S (2016) Geroscience approaches to increase healthspan and slow aging. F1000Res. doi:10.12688/f1000research.7583.1
28. Consortium THMP (2012) Structure, function and diversity of the healthy human microbiome. Nature 486(7402):207–214. doi:10.1038/nature11234
29. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J, Weissenbach J, Ehrlich SD, Bork P (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180. doi:10.1038/nature09944
30. Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A, McDonald D, Knight R (2014) Rethinking “Enterotypes”. Cell Host Microbe 16(4):433–437. doi:10.1016/j.chom.2014.09.013
31. Derrien M, Vlieg JETvH (2015) Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol 23(6):354–366. doi:10.1016/j.tim.2015.03.002
32. Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, Weerd Hd, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, Dv Sinderen, O’Connor M, Harnedy N, O’Connor K, Henry C, O’Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O’Toole PW (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci 108(Supplement 1):4586–4591. doi:10.1073/pnas.1000097107
33. Mariat D, Firmesse O, Levenez F, Guimarăes VD, Sokol H, Doré J, Corthier G, Furet JP (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123. doi:10.1186/1471-2180-9-123
34. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. doi:10.1371/journal.pone.0010667
35. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184. doi:10.1038/nature11319
36. Jeffery IB, Lynch DB, O’Toole PW (2016) Composition and temporal stability of the gut microbiota in older persons. ISME J 10(1):170–182. doi:10.1038/ismej.2015.88
37. van Tongeren SP, Slaets JPJ, Harmsen HJM, Welling GW (2005) Fecal microbiota composition and frailty. Appl Environ Microbiol 71(10):6438–6442. doi:10.1128/AEM.71.10.6438-6442
38. Jackson MA, Jeffery IB, Beaumont M, Bell JT, Clark AG, Ley RE, O’Toole PW, Spector TD, Steves CJ (2016) Signatures of early frailty in the gut microbiota. Genome Med. doi:10.1186/s13073-016-0262-7
39. Langille MGI, Meehan CJ, Koenig JE, Dhanani AS, Rose RA, Howlett SE, Beiko RG (2014) Microbial shifts in the aging mouse gut. Microbiome. doi:10.1186/s40168-014-0050-9
40. Samuel BS, Rowedder H, Braendle C, Félix M-A, Ruvkun G (2016) Caenorhabditis elegans responses to bacteria from its natural habitats. Proc Natl Acad Sci 113(27):E3941–E3949. doi:10.1073/pnas.1607183113
41. Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, Mader S, Petersen C, Kowallik V, Rosenstiel P, Félix M-A, Schulenburg H (2016) The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model. BMC Biol. doi:10.1186/s12915-016-0258-1
42. Wong ACN, Chaston JM, Douglas AE (2013) The inconstant gut microbiota of Drosophila species revealed by 16S rRNA gene analysis. ISME J 7(10):1922–1932. doi:10.1038/ismej.2013.86
43. Chandler JA, Morgan Lang J, Bhatnagar S, Eisen JA, Kopp A (2011) Bacterial communities of diverse Drosophila species: ecological context of a host–microbe model system. PLoS Genet. doi:10.1371/journal.pgen.1002272
44. Corby-Harris V, Pontaroli AC, Shimkets LJ, Bennetzen JL, Habel KE, Promislow DEL (2007) Geographical distribution and diversity of bacteria associated with natural populations of Drosophila melanogaster. Appl Environ Microbiol 73(11):3470–3479. doi:10.1128/AEM.02120-06
45. Cox CR, Gilmore MS (2007) Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis. Infect Immun 75(4):1565–1576. doi:10.1128/IAI.01496-06
46. Wong ACN, Luo Y, Jing X, Franzenburg S, Bost A, Douglas AE (2015) The host as the driver of the microbiota in the gut and external environment of Drosophila melanogaster. Appl Environ Microbiol 81(18):6232–6240. doi:10.1128/AEM.01442-15
47. Storelli G, Defaye A, Erkosar B, Hols P, Royet J, Leulier F (2011) Lactobacillus plantarum promotes drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab 14(3):403–414. doi:10.1016/j.cmet.2011.07.012
48. Shin SC, Kim S-H, You H, Kim B, Kim AC, Lee K-A, Yoon J-H, Ryu J-H, Lee W-J (2011) Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334(6056):670–674. doi:10.1126/science.1212782
49. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161(3):1101–1112
50. Portal-Celhay C, Bradley ER, Blaser MJ (2012) Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans. BMC Microbiol 12:49. doi:10.1186/1471-2180-12-49
51. Gomez F, Monsalve GC, Tse V, Saiki R, Weng E, Lee L, Srinivasan C, Frand AR, Clarke CF (2012) Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli. BMC Microbiol 12:300. doi:10.1186/1471-2180-12-300
52. Erkosar B, Storelli G, Defaye A, Leulier F (2013) Host-intestinal microbiota mutualism: “learning on the fly”. Cell Host Microbe 13(1):8–14. doi:10.1016/j.chom.2012.12.004
53. Broderick NA, Lemaitre B (2012) Gut-associated microbes of Drosophila melanogaster. Gut Microbes 3(4):307–321. doi:10.4161/gmic.19896
54. Clark RI, Salazar A, Yamada R, Fitz-Gibbon S, Morselli M, Alcaraz J, Rana A, Rera M, Pellegrini M, Ja WW, Walker DW (2015) Distinct shifts in microbiota composition during drosophila aging impair intestinal function and drive mortality. Cell Rep 12(10):1656–1667. doi:10.1016/j.celrep.2015.08.004
55. Broderick NA, Buchon N, Lemaitre B (2014) Microbiota-induced changes in Drosophila melanogaster host gene expression and gut morphology. MBio 5(3):e01117–e01214. doi:10.1128/mBio.01117-14
56. Buchon N, Broderick NA, Chakrabarti S, Lemaitre B (2009) Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23(19):2333–2344. doi:10.1101/gad.1827009
57. Ren C, Webster P, Finkel SE, Tower J (2007) Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab 6(2):144–152. doi:10.1016/j.cmet.2007.06.006
58. McGee MD, Weber D, Day N, Vitelli C, Crippen D, Herndon LA, Hall DH, Melov S (2011) Loss of intestinal nuclei and intestinal integrity in aging C. elegans. Aging Cell 10(4):699–710. doi:10.1111/j.1474-9726.2011.00713.x
59. Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3(4):442–455. doi:10.1016/j.stem.2008.07.024
60. Choi N-H, Kim J-G, Yang D-J, Kim Y-S, Yoo M-A (2008) Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell 7(3):318–334. doi:10.1111/j.1474-9726.2008.00380.x
61. Park J-S, Kim Y-S, Yoo M-A (2009) The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila. Aging 1(7):637–651. doi:10.18632/aging.100054
62. Li H, Jasper H (2016) Gastrointestinal stem cells in health and disease: from flies to humans. Dis Models Mech 9(5):487–499. doi:10.1242/dmm.024232
63. Chen H, Zheng X, Zheng Y (2014) Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell 159(4):829–843. doi:10.1016/j.cell.2014.10.028
64. Petkau K, Parsons BD, Duggal A, Foley E (2014) A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila. J Biol Chem 289(41):28719–28729. doi:10.1074/jbc.M114.578708
65. Rera M, Clark RI, Walker DW (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci USA 109(52):21528–21533. doi:10.1073/pnas.1215849110
66. Dambroise E, Monnier L, Ruisheng L, Aguilaniu H, Joly JS, Tricoire H, Rera M (2016) Two phases of aging separated by the Smurf transition as a public path to death. Sci Rep. doi:10.1038/srep23523
67. Gelino S, Chang JT, Kumsta C, She X, Davis A, Nguyen C, Panowski S, Hansen M (2016) Intestinal autophagy improves healthspan and longevity in C. elegans during dietary restriction. PLoS Genet. doi:10.1371/journal.pgen.1006135
68. Kavanagh K, Brown RN, Davis AT, Uberseder B, Floyd E, Pfisterer B, Shively CA (2016) Microbial translocation and skeletal muscle in young and old vervet monkeys. Age (Dordrecht, Netherlands) 38(3):58. doi:10.1007/s11357-016-9924-z
69. Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larché MJ, Davidson DJ, Verdú EF, Surette MG, Bowdish DME (2017) Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21(4):455.e454–466.e454. doi:10.1016/j.chom.2017.03.002
70. Karpac J, Biteau B, Jasper H (2013) Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell reports. doi:10.1016/j.celrep.2013.08.004
71. Houthoofd K, Braeckman BP, Lenaerts I, Brys K, De Vreese A, Van Eygen S, Vanfleteren JR (2002) Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Exp Gerontol 37(12):1371–1378
72. Brummel T, Ching A, Seroude L, Simon AF, Benzer S (2004) Drosophila lifespan enhancement by exogenous bacteria. Proc Natl Acad Sci USA 101(35):12974–12979. doi:10.1073/pnas.0405207101
73. Yamada R, Deshpande SA, Bruce KD, Mak EM, Ja WW (2015) Microbes promote amino acid harvest to rescue undernutrition in Drosophila. Cell Rep. doi:10.1016/j.celrep.2015.01.018
74. Gems D, Riddle DL (2000) Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154(4):1597–1610
75. Larsen PL, Clarke CF (2002) Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 295(5552):120–123. doi:10.1126/science.1064653
76. Saiki R, Lunceford AL, Bixler T, Dang P, Lee W, Furukawa S, Larsen PL, Clarke CF (2008) Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q. Aging Cell 7(3):291–304. doi:10.1111/j.1474-9726.2008.00378.x
77. Virk B, Jia J, Maynard CA, Raimundo A, Lefebvre J, Richards SA, Chetina N, Liang Y, Helliwell N, Cipinska M, Weinkove D (2016) Folate acts in E. coli to accelerate C. elegans aging independently of bacterial biosynthesis. Cell Rep 14(7):1611–1620. doi:10.1016/j.celrep.2016.01.051
78. Sanchez-Blanco A, Kim SK (2011) Variable pathogenicity determines individual lifespan in Caenorhabditis elegans. PLoS Genet 7(4):e1002047. doi:10.1371/journal.pgen.1002047
79. Khanna A, Kumar J, Vargas MA, Barrett L, Katewa S, Li P, McCloskey T, Sharma A, Naude N, Nelson C, Brem R, Killilea DW, Mooney SD, Gill M, Kapahi P (2016) A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans. Sci Rep 6:38764. doi:10.1038/srep38764
80. Virk B, Correia G, Dixon DP, Feyst I, Jia J, Oberleitner N, Briggs Z, Hodge E, Edwards R, Ward J, Gems D, Weinkove D (2012) Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model. BMC Biol 10:67. doi:10.1186/1741-7007-10-67
81. Heintz C, Mair W (2014) You are what you host: microbiome modulation of the aging process. Cell 156(3):408–411. doi:10.1016/j.cell.2014.01.025
82. Gusarov I, Gautier L, Smolentseva O, Shamovsky I, Eremina S, Mironov A, Nudler E (2013) Bacterial nitric oxide extends the lifespan of C. elegans. Cell 152(4):818–830. doi:10.1016/j.cell.2012.12.043
83. Liu H, Wang X, Wang HD, Wu J, Ren J, Meng L, Wu Q, Dong H, Wu J, Kao TY, Ge Q, Wu ZX, Yuh CH, Shan G (2012) Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans. Nat Commun 3:1073. doi:10.1038/ncomms2071
84. Burkewitz K, Zhang Y, Mair WB (2014) AMPK at the nexus of energetics and aging. Cell Metab 20(1):10–25. doi:10.1016/j.cmet.2014.03.002
85. Gelino S, Hansen M (2012) Autophagy—an emerging anti-aging mechanism. J Clin Exp Pathol (Suppl 4):006
86. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11(6):453–465. doi:10.1016/j.cmet.2010.05.001
87. Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G (2009) Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev 23(4):496–511. doi:10.1101/gad.1775409
88. Pang S, Curran SP (2014) Adaptive capacity to bacterial diet modulates aging in C. elegans. Cell Metab 19(2):221–231. doi:10.1016/j.cmet.2013.12.005
89. Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cocheme HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D (2013) Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153(1):228–239. doi:10.1016/j.cell.2013.02.035
90. Craven M, Egan CF, Dowd SE, McDonough SP, Dogan B, Denkers EY, Bowman D, Scherl EJ, Simpson KW (2012) Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn’s disease. PLoS One 7(7):e41594. doi:10.1371/journal.pone.0041594
91. Dantoft W, Lundin D, Esfahani S, Engstrom Y (2016) The POU/Oct transcription factor Pdm1/nub Is necessary for a beneficial gut microbiota and normal lifespan of Drosophila. J Innate Immun 8(4):412–426. doi:10.1159/000446368
92. Lewis James D, Chen Eric Z, Baldassano Robert N, Otley Anthony R, Griffiths Anne M, Lee D, Bittinger K, Bailey A, Friedman Elliot S, Hoffmann C, Albenberg L, Sinha R, Compher C, Gilroy E, Nessel L, Grant A, Chehoud C, Li H, Wu Gary D, Bushman Frederic D (2015) Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18(4):489–500. doi:10.1016/j.chom.2015.09.008