Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14.
Ramakrishna BS. Role of the gut microbiota in human nutrition and metabolism. J Gastroenterol Hepatol. 2013;28 Suppl 4:9–17.
Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787–803.
Dubos R. Man adapting. New Haven: Yale University Press; 1965.
Dubos R, Savage D, Schaedler R. Biological Freudianism. Lasting effects of early environmental influences. Pediatrics. 1966;38(5):789–800.
Pearce N, Ebrahim S, McKee M, Lamptey P, Barreto ML, Matheson D, et al. Global prevention and control of NCDs: limitations of the standard approach. J Public Health Policy. 2015;36(4):408–25.
Trojan TD, Khan DA, Defina LF, Akpotaire O, Goodwin RD, Brown ES. Asthma and depression: the Cooper Center Longitudinal Study. Ann Allergy Asthma Immunol. 2014;112(5):432–6.
Prescott SL. Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases. J Allergy Clin Immunol. 2013;131(1):23–30.
West CE, Renz H, Jenmalm MC, Kozyrskyj AL, Allen KJ, Vuillermin P, et al. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol. 2015;135(1):3–13. A recent summary of the multisystem implications of dysbiosis on long-term health and the particular importance of establishment of the microbiota in early life.
Rook GA. Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc Natl Acad Sci U S A. 2013;110(46):18360–7.
Relman D. The human microbiome and the future practice of medicine. JAMA. 2015;314(11):1127–8.
Fugmann SD. The origins of the RAG genes—from transposition to V(D)J recombination. Semin Immunol. 2010;22:10–6.
Rebollo R, Horard B, Hubert B, Vieira C. Jumping genes and epigenetics: towards new species. Gene. 2010;454:1–7.
Zeh DW, Zeh JA, Ishida Y. Transposable elements and an epigenetic basis for punctuated equilibria. Bioessays. 2009;31:715–26.
Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 2007;8(4):272–85.
Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–73.
Salvucci E. Microbiome, holobiont and the net of life. Crit Rev Microbiol. 2014;28:1–10.
Weaver CT, Hatton RD. Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol. 2009;9(12):883–9.
Prescott S, Macaubas C, Smallacombe T, Holt B, Sly P, Loh R, et al. Development of allergen-specific T-cell memory in atopic and normal children. Lancet. 1999;353(9148):196–200.
Tulic MK, Hodder M, Forsberg A, McCarthy S, Richman T, D’Vaz N, et al. Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny. J Allergy Clin Immunol. 2011;127:470–8. e1.
Tulic MK, Andrews D, Crook ML, Charles A, Tourigny MR, Moqbel R, et al. Changes in thymic regulatory T-cell maturation from birth to puberty: differences in atopic children. J Allergy Clin Immunol. 2012;129:199–206. e1-4.
Prescott S, Macaubas C, Holt B, Smallacombe T, Loh R, Sly P, et al. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T-cell responses towards Th-2 cytokine profile. J Immunol. 1998;160:4730–7.
West CE, Jenmalm MC, Prescott SL. The gut microbiota and its role in the development of allergic disease: a wider perspective. Clin Exp Allergy. 2015;45:43–53.
Schaub B, Liu J, Hoppler S, Schleich I, Huehn J, Olek S, et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol. 2009;123:774–82. e5.
Riedler J, Eder W, Oberfeld G, Schreuer M. Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy. 2000;30:194–200.
Ege MJ, Bieli C, Frei R, van Strien RT, Riedler J, Ublagger E, et al. Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol. 2006;117:817–23.
Wlasiuk G, Vercelli D. The farm effect, or: when, what and how a farming environment protects from asthma and allergic disease. Curr Opin Allergy Clin Immunol. 2012;12:461–6.
Michel S, Busato F, Genuneit J, Pekkanen J, Dalphin JC, Riedler J, et al. Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Allergy. 2013;68(3):355–64.
Lluis A, Depner M, Gaugler B, Saas P, Casaca VI, Raedler D, et al. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood. J Allergy Clin Immunol. 2014;133:551–9.
Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol. 2012;129:434–40. 40 e1-2.
Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014;44:842–50.
Blumer N, Herz U, Wegmann M, Renz H. Prenatal lipopolysaccharide-exposure prevents allergic sensitisation and airway inflammation, but not airway responsiveness in a murine model of experimental asthma. Clin Exp Allergy. 2005;35:397–402.
Blumer N, Sel S, Virna S, Patrascan CC, Zimmermann S, Herz U, et al. Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clin Exp Allergy. 2007;37:348–57.
Conrad ML, Ferstl R, Teich R, Brand S, Blumer N, Yildirim AO, et al. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med. 2009;206:2869–77.
Brand S, Teich R, Dicke T, Harb H, Yildirim AO, Tost J, et al. Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes. J Allergy Clin Immunol. 2011;128:618–25. e1-7.
Rautava S, Collado MC, Salminen S, Isolauri E. Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology. 2012;102:178–84.
Thorburn AN, McKenzie CI, Shen S, Stanley D, Macia L, Mason LJ, et al. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat Commun. 2015;6:7320. An elegant demonstration of that maternal dietary fibre in pregnancy can prevent an allergic phenotype in the offspring, and these effects are mediated by altered gut microbiota and short-chain fatty acid (SCFA) production. Moreover, the same effects can be achieved by SCFA directly.
Yu DH, Gadkari M, Zhou Q, Yu S, Gao N, Guan Y, et al. Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome. Genome Biol. 2015;16(1):21. Demonstrates that the gut microbiome shapes the epigenetic development of intestinal stem cells with potential lifelong implications for health.
Heindel JJ, Balbus J, Birnbaum L, Brune-Drisse MN, Grandjean P, Gray K, et al. Developmental origins of health and disease: integrating environmental influences. Endocrinology. 2015;156(10):3416–21.
Rodríguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. Summarises the developmental patterns of the gut microbiota, the early life influences, and the long term implications.
Moles L, Gómez M, Heilig H, Bustos G, Fuentes S, de Vos W, et al. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013;8(6):e66986.
Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65.
Zijlmans MA, Korpela K, Riksen-Walraven JM, de Vos WM, de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–45.
Hollister EB, Riehle K, Luna RA, Weidler EM, Rubio-Gonzales M, Mistretta TA, et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome. 2015;3:36. Shows that the gut microbiome may undergo a more prolonged development than previously suspected with persistent compositional and functional differences in the healthy pre-adolescent gut compared with healthy adults.
Avershina E, Rudi K. Confusion about the species richness of human gut microbiota. Benefic Microbes. 2015;6(5):657–9.
Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015;33(9):496–503. Healthy human gut flora normally include only a minor proportion of Proteobacteria. This review explores how abnormal expansion of this phylum compromises the ability to maintain a balanced gut microbial community, as a potential diagnostic signature of dysbiosis and risk of disease.
Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2015 Sep 2.
Albenberg LG, Wu GD. Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology. 2014;146(6):1564–72.
Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015;7(307):307ra152. Identifies a potential ‘critical window’ in the first 100 days in which reduced abundance of protective genera (notably Lachnospira, Veillonella, Faecalibacterium and Rothia) increased risk of subsequent asthma in children, and associated with reduced levels of faecal acetate and dysregulation of enterohepatic metabolites which have recognised immunomodulatory properties.
Segata N. Gut microbiome: westernization and the disappearance of intestinal diversity. Curr Biol. 2015;25(14):R611–3.
Furney EE. Culture: a modern method. St. Louis: Nixon Jones Printing Co; 1890.
Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16:1024.
Logan AC. Dysbiotic drift: mental health, environmental grey space, and microbiota. J Physiol Anthropol. 2015;34(1):23.
Logan AC, Jacka FN. Nutritional psychiatry research: an emerging discipline and its intersection with global urbanization, environmental challenges and the evolutionary mismatch. J Physiol Anthropol. 2014;33:22.
Azzini E, Polito A, Fumagalli A, Intorre F, Venneria E, Durazzo A, et al. Mediterranean diet effect: an Italian picture. Nutr J. 2011;10:125.
Rice JL, Romero KM, Galvez Davila RM, Meza CT, Bilderback A, Williams DL. Association between adherence to the Mediterranean diet and asthma in Peruvian children. Lung. 2015;193(6):893–9. 78,79.
Sánchez-Villegas A, Henríquez-Sánchez P, Ruiz-Canela M, Lahortiga F, Molero P, Toledo E, et al. A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. BMC Med. 2015;13:197.
Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–90.
De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2015 Sep 28. Compares gut microbiota and metabolome in individuals habitually following omnivore, vegetarian or vegan diets, and detected significant associations between consumption of vegetable-based diets and increased levels of faecal SCFA, Prevotella and fibre-degrading Firmicutes. Demonstrates the effects of dietary patterns on beneficial microbiome-related metabolomic profiles.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63. Demonstrates that the human gut microbiome can rapidly respond to dietary changes (e.g. plant-based versus animal-based diet) with compositional and metabolic changes within days.
Xu Z, Knight R. Dietary effects on human gut microbiome diversity. Br J Nutr. 2015;113(Suppl):S1–5.
Tap J, Furet JP, Bensaada M, Philippe C, Roth H, Rabot S, et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ Microbiol. 2015. A 6-week nutritional trial: healthy adults consumed diet supplemented with varying amounts of dietary fibre followed washout periods, showing that short-term dietary change did not have the same impact for all individuals, but generally increased microbiota richness and microbiota stability, and modulated the expression of numerous microbiota metabolic pathways.
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–8.
Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6.
Herlitz GN, Arlow RL, Cheung NH, Coyle SM, Griffel B, Macor MA, et al. Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin. Shock. 2015;43(2):133–9.
Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58(5):445–52.
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci U S A. 2015;112(40):12468–73. The first humans study using positron emission tomography (PET) to demonstrate that the increase in blood levels of inflammatory cytokines induced by a systemic LPS challenge acutely induces microglial activation in the brain.
Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, et al. Intestinal permeability—a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189.
Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392.
Yirmiya R, Rimmerman N, Reshef R. Depression as a microglial disease. Trends Neurosci. 2015;38(10):637–58.
Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–77. Demonstrates substantial contributions of the gut microbiota to microglia homeostasis, maturation and function in the brain, and how this can be temporally modulated by eradication of host microbiota or by dietary changes. Also shows that some of these effects are mediated via SCFA metabolites.
Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2015 Jun 22.
Cani PD, Everard A. Talking microbes: when gut bacteria interact with diet and host organs. Mol Nutr Food Res. 2015.
Ghosh SS, Bie J, Wang J, Ghosh S. Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR−/− mice—role of intestinal permeability and macrophage activation. PLoS One. 2014;9(9):e108577.
Kaliannan K, Wang B, Li XY, Kim KJ, Kang JX. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-6 fatty acids on metabolic endotoxemia. Sci Rep. 2015;5:11276.
Kelly CJ, Colgan SP, Frank DN. Of microbes and meals: the health consequences of dietary endotoxemia. Nutr Clin Pract. 2012;27(2):215–25.
Cardinale BJ, Duffy JE, Gonzalez A, Hooper DU, Perrings C, Venail P, et al. Biodiversity loss and its impact on humanity. Nature. 2012;486(7401):59–67.
Watts N, Adger WN, Agnolucci P, Blackstock J, Byass P, Cai W, et al. Health and climate change: policy responses to protect public health. Lancet. 2015 Jun 24.
Lovell R, Wheeler BW, Higgins SL, Irvine KN, Depledge MH. A systematic review of the health and well-being benefits of biodiverse environments. J Toxicol Environ Health B Crit Rev. 2014;17(1):1–20.
Haahtela T, Holgate S, Pawankar R, Akdis CA, Benjaponpitak S, Caraballo L, et al. The biodiversity hypothesis and allergic disease: world allergy organization position statement. World Allergy Organ J. 2013;6(1):3.
von Hertzen L, Beutler B, Bienenstock J, Blaser M, Cani PD, Eriksson J, et al. Helsinki alert of biodiversity and health. Ann Med. 2015;47(3):218–25.
Valkonen M, Wouters IM, Täubel M, Rintala H, Lenters V, Vasara R, et al. Bacterial exposures and associations with atopy and asthma in children. PLoS One. 2015;10(6):e0131594.
McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci U S A. 2012;109 Suppl 2:17281–8.
Hospodsky D, Pickering AJ, Julian TR, Miller D, Gorthala S, Boehm AB, et al. Hand bacterial communities vary across two different human populations. Microbiology. 2014;160(Pt 6):1144–52.
Ruokolainen L, von Hertzen L, Fyhrquist N, Laatikainen T, Lehtomäki J, Auvinen P, et al. Green areas around homes reduce atopic sensitization in children. Allergy. 2015;70(2):195–202.
Hanski I, von Hertzen L, Fyhrquist N, Koskinen K, Torppa K, Laatikainen T, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci U S A. 2012;109(21):8334–9.
Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL. The microbiome extends to subepidermal compartments of normal skin. Nat Commun. 2013;4:1431.
Wislicenus GA. Oneness of life, fundamentals III. Contact Point. 1933;10(5):137–40.
Ueda P, Tong L, Viedma C, Chandy SJ, Marrone G, et al. Food marketing towards children: brand logo recognition, food-related behavior and BMI among 3-13-year-olds in a south Indian town. PLoS One. 2012;7(10):e47000.
Sarris J, Logan AC, Akbaraly TN, Amminger GP, Balanzá-Martínez V, Freeman MP. Lancet Psychiatry. 2015;2(3):271–4.
Dominguez-Bello MG, Blaser MJ. Asthma: undoing millions of years of coevolution in early life? Sci Transl Med. 2015;7(307):307fs39.
Galley JD, Bailey M, Kamp Dush C, Schoppe-Sullivan S, Christian LM. Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS One. 2014;9(11):e113026.
Goyal MS, Venkatesh S, Milbrandt J, Gordon JI, Raichle ME. Feeding the brain and nurturing the mind: linking nutrition and the gut microbiota to brain development. Proc Natl Acad Sci U S A. 2015;112(46):14105–12.