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A. Woolcock, J. Peat (2007)Evidence for the increase in asthma worldwide.
Ciba Foundation symposium, 206
(2017)This study demonstrates the utility of microbiota transfer approaches for the treatment of a neurological disorder of high prevalence and societal cost
M. Kalliomäki, P. Kirjavainen, E. Eerola, P. Kero, S. Salminen, E. Isolauri (2001)Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.
The Journal of allergy and clinical immunology, 107 1
Rishu Dheer, J. Patterson, M. Dudash, E. Stachler, K. Bibby, D. Stolz, S. Shiva, Zeneng Wang, S. Hazen, A. Barchowsky, J. Stolz (2015)Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.
Toxicology and applied pharmacology, 289 3
S. Dogra, O. Sakwinska, S. Soh, C. Ngom-Bru, W. Brück, B. Berger, H. Brüssow, Y. Lee, F. Yap, Y. Chong, K. Godfrey, J. Holbrook (2015)Dynamics of Infant Gut Microbiota Are Influenced by Delivery Mode and Gestational Duration and Are Associated with Subsequent Adiposity
J. Penders, C. Thijs, P. Brandt, I. Kummeling, Bianca Snijders, F. Stelma, H. Adams, R. Ree, E. Stobberingh (2006)Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study
Yvonne Vallè, A. Artacho, A. Pascual-García, Maria Ferrú, M. Gosalbes, Juan Abellá, M. Francino, D. Guttman (2014)Microbial Succession in the Gut: Directional Trends of Taxonomic and Functional Change in a Birth Cohort of Spanish Infants
PLoS Genetics, 10
A. Platt, A. Mowat (2008)Mucosal macrophages and the regulation of immune responses in the intestine.
Immunology letters, 119 1-2
G. Kaplan, J. Hubbard, J. Korzenik, B. Sands, R. Panaccione, Subrata Ghosh, A. Wheeler, P. Villeneuve (2010)The Inflammatory Bowel Diseases and Ambient Air Pollution: A Novel Association
The American Journal of Gastroenterology, 105
M. Collado, S. Rautava, J. Aakko, E. Isolauri, S. Salminen (2016)Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid
Scientific Reports, 6
H. Bisgaard, Nan Li, K. Bønnelykke, B. Chawes, T. Skov, G. Paludan-Müller, J. Stokholm, Birgitte Smith, K. Krogfelt (2011)Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age.
The Journal of allergy and clinical immunology, 128 3
E. Jiménez, M. Marín, Rocío Martín, J. Odriozola, M. Olivares, J. Xaus, L. Fernández, J. Rodríguez (2008)Is meconium from healthy newborns actually sterile?
Research in microbiology, 159 3
J. Madan, A. Hoen, S. Lundgren, S. Farzan, K. Cottingham, H. Morrison, M. Sogin, Hongzhe Li, J. Moore, M. Karagas (2016)Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants.
JAMA pediatrics, 170 3
T. Mosmann, H. Cherwinski, M. Bond, M. Giedlin, R. Coffman (1986)Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
Journal of immunology, 136 7
C. Benn, M. Melbye, J. Wohlfahrt, B. Björkstén, P. Aaby (2004)Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life
BMJ : British Medical Journal, 328
S. Langley-Evans (2015)Fetal nutrition and disease in later life
C. Huttenhower, D. Gevers, R. Knight, Sahar Abubucker, J. Badger, A. Chinwalla, H. Creasy, A. Earl, Michael Fitzgerald, R. Fulton, M. Giglio, Kymberlie Hallsworth-Pepin, E. Lobos, R. Madupu, V. Magrini, John Martin, M. Mitreva, D. Muzny, E. Sodergren, J. Versalovic, A. Wollam, K. Worley, J. Wortman, Sarah Young, Qiandong Zeng, K. Aagaard, Olukemi Abolude, E. Allen-Vercoe, E. Alm, Lucia Alvarado, G. Andersen, S. Anderson, Elizabeth Appelbaum, H. Arachchi, G. Armitage, Cesar Arze, T. Ayvaz, Carl Baker, L. Begg, Tsegahiwot Belachew, Veena Bhonagiri, Monika Bihan, M. Blaser, Toby Bloom, Vivien Bonazzi, J. Brooks, G. Buck, C. Buhay, D. Busam, Joseph Campbell, S. Canon, B. Cantarel, P. Chain, I. Chen, Lei Chen, Shaila Chhibba, Ken Chu, Dawn Ciulla, J. Clemente, S. Clifton, S. Conlan, J. Crabtree, M. Cutting, Noam Davidovics, Catherine Davis, T. DeSantis, C. Deal, Kimberley Delehaunty, F. Dewhirst, E. Deych, Yan Ding, D. Dooling, Shannon Dugan, W. Dunne, A. Durkin, Robert Edgar, R. Erlich, Candace Farmer, R. Farrell, Karoline Faust, M. Feldgarden, Victor Felix, Sheila Fisher, A. Fodor, L. Forney, Les Foster, V. Francesco, Jonathan Friedman, Dennis Friedrich, C. Fronick, L. Fulton, Hongyu Gao, Nathalia Garcia, G. Giannoukos, C. Giblin, Maria Giovanni, J. Goldberg, Johannes Goll, Antonio Gonzalez, Allison Griggs, Sharvari Gujja, S. Haake, B. Haas, Holli Hamilton, Emily Harris, Theresa Hepburn, Brandi Herter, D. Hoffmann, M. Holder, Clinton Howarth, Katherine Huang, S. Huse, J. Izard, J. Jansson, Huaiyang Jiang, Catherine Jordan, Vandita Joshi, J. Katancik, W. Keitel, S. Kelley, C. Kells, N. King, D. Knights, H. Kong, O. Koren, S. Koren, Karthik Kota, C. Kovar, N. Kyrpides, P. Rosa, Sandy Lee, K. Lemon, N. Lennon, Cecil Lewis, L. Lewis, R. Ley, Kelvin Li, K. Liolios, Bo Liu, Yue Liu, C. Lo, C. Lozupone, R. Lunsford, T. Madden, A. Mahurkar, P. Mannon, E. Mardis, V. Markowitz, K. Mavromatis, J. McCorrison, Daniel McDonald, J. Mcewen, A. McGuire, P. Mcinnes, Teena Mehta, K. Mihindukulasuriya, J. Miller, P. Minx, I. Newsham, C. Nusbaum, M. O'Laughlin, Joshua Orvis, I. Pagani, Krishna Palaniappan, Shital Patel, Matthew Pearson, Jane Peterson, M. Podar, C. Pohl, K. Pollard, Mihai Pop, M. Priest, L. Proctor, X. Qin, J. Raes, J. Ravel, J. Reid, Mina Rho, R. Rhodes, Kevin Riehle, M. Rivera, B. Rodriguez-Mueller, Y. Rogers, M. Ross, C. Russ, Ravi Sanka, P. Sankar, J. Sathirapongsasuti, J. Schloss, P. Schloss, T. Schmidt, M. Scholz, L. Schriml, Alyxandria Schubert, N. Segata, J. Segre, W. Shannon, R. Sharp, T. Sharpton, N. Shenoy, N. Sheth, Gina Simone, Indresh Singh, C. Smillie, J. Sobel, Daniel Sommer, P. Spicer, G. Sutton, S. Sykes, D. Tabbaa, M. Thiagarajan, Chad Tomlinson, M. Torralba, T. Treangen, R. Truty, T. Vishnivetskaya, Jason Walker, Lu Wang, Zhengyuan Wang, D. Ward, W. Warren, M. Watson, Christopher Wellington, K. Wetterstrand, J. White, Katarzyna Wilczek-Boney, Yuanqing Wu, K. Wylie, T. Wylie, C. Yandava, Liang Ye, Yuzhen Ye, Shibu Yooseph, Bonnie Youmans, Lan Zhang, Yanjiao Zhou, Yiming Zhu, L. Zoloth, Jeremy Zucker, B. Birren, R. Gibbs, S. Highlander, B. Methé, K. Nelson, J. Petrosino, G. Weinstock, R. Wilson, O. White (2012)Structure, Function and Diversity of the Healthy Human Microbiome
P. Turnbaugh, F. Bäckhed, L. Fulton, J. Gordon (2008)Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome.
Cell host & microbe, 3 4
E. Sepp, K. Julge, M. Mikelsaar, B. Björkstén (2005)Intestinal microbiota and immunoglobulin E responses in 5‐year‐old Estonian children
Clinical & Experimental Allergy, 35
E. Mutius, F. Martinez, C. Fritzsch, T. Nicolai, P. Reitmeir, H. Thiemann (1994)Skin test reactivity and number of siblings
Sharon Herring, Marisa Rose, Helen Skouteris, Emily Oken (2012)Optimizing weight gain in pregnancy to prevent obesity in women and children
Mei Wang, Caroline Karlsson, C. Olsson, I. Adlerberth, A. Wold, D. Strachan, Paolo Martricardi, N. Åberg, M. Perkin, S. Tripodi, A. Coates, B. Hesselmar, R. Saalman, G. Molin, S. Ahrné (2008)Reduced diversity in the early fecal microbiota of infants with atopic eczema.
The Journal of allergy and clinical immunology, 121 1
D. Leitner, G. Frühbeck, V. Yumuk, K. Schindler, D. Micić, E. Woodward, H. Toplak (2017)Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way
Obesity Facts, 10
E. Hsiao, S. Mcbride, S. Hsien, G. Sharon, Embriette Hyde, Tyler McCue, Julian Codelli, J. Chow, S. Reisman, J. Petrosino, P. Patterson, S. Mazmanian (2013)Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders
Whanhee Lee, Jee-Young Choo, J. Son, Ho Kim (2016)Association between long-term exposure to air pollutants and prevalence of cardiovascular disease in 108 South Korean communities in 2008-2010: A cross-sectional study.
The Science of the total environment, 565
S. Duncan, G. Lobley, G. Holtrop, J. Ince, A. Johnstone, P. Louis, H. Flint (2008)Human colonic microbiota associated with diet, obesity and weight loss
International Journal of Obesity, 32
C. Mulligan, J. Friedman (2017)Maternal modifiers of the infant gut microbiota: metabolic consequences.
The Journal of endocrinology, 235 1
Clare Murray, G. Tannock, M. Simon, H. Harmsen, Gjalt Welling, Adnan Custovic, Ashley Woodcock (2005)Fecal microbiota in sensitized wheezy and non‐sensitized non‐wheezy children: a nested case–control study
Clinical & Experimental Allergy, 35
J. Swanson, S. Entringer, C. Buss, P. Wadhwa (2009)Developmental origins of health and disease: environmental exposures.
Seminars in reproductive medicine, 27 5
E. Jiménez, L. Fernández, M. Marín, Rocío Martín, J. Odriozola, Carmen Nueno-Palop, A. Narbad, M. Olivares, J. Xaus, J. Rodríguez (2005)Isolation of Commensal Bacteria from Umbilical Cord Blood of Healthy Neonates Born by Cesarean Section
Current Microbiology, 51
K. Aagaard, Jun Ma, K. Antony, R. Ganu, J. Petrosino, J. Versalovic (2014)The Placenta Harbors a Unique Microbiome
Science Translational Medicine, 6
S. Dogra, O. Sakwinska, S. Soh, C. Ngom-Bru, W. Brück, B. Berger, H. Brüssow, N. Karnani, Y. Lee, F. Yap, Y. Chong, K. Godfrey, J. Holbrook (2015)Rate of establishing the gut microbiota in infancy has consequences for future health
Gut Microbes, 6
T. Gajewski, F. Fitch (1988)Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones.
Journal of immunology, 140 12
P. Pérez, J. Doré, M. Leclerc, F. Levenez, J. Benyacoub, P. Serrant, I. Segura-Roggero, E. Schiffrin, A. Donnet-Hughes (2007)Bacterial Imprinting of the Neonatal Immune System: Lessons From Maternal Cells?
J. Breton, S. Massart, P. Vandamme, E. Brandt, B. Pot, B. Foligné (2013)Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome
BMC Pharmacology & Toxicology, 14
T. Weid, C. Bulliard, E. Schiffrin (2001)Induction by a Lactic Acid Bacterium of a Population of CD4+ T Cells with Low Proliferative Capacity That Produce Transforming Growth Factor β and Interleukin-10
Clinical Diagnostic Laboratory Immunology, 8
D. Strachan (2000)Family size, infection and atopy: the first decade of the 'hygiene hypothesis'
J. Amar, C. Chabo, A. Waget, P. Klopp, C. Vachoux, L. Bermúdez-Humarán, N. Smirnova, M. Bergé, T. Sulpice, S. Lahtinen, A. Ouwehand, P. Langella, N. Rautonen, P. Sansonetti, R. Burcelin (2011)Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment
EMBO Molecular Medicine, 3
I. Kuvaeva, N. Orlova, O. Veselova, G. Kuznezova, T. Borovik (1984)Microecology of the gastrointestinal tract and the immunological status under food allergy.
Die Nahrung, 28 6-7
P. Louis (2012)Does the Human Gut Microbiota Contribute to the Etiology of Autism Spectrum Disorders?
Digestive Diseases and Sciences, 57
I. Sekirov, Shannon Russell, L. Antunes, B. Finlay (2010)Gut microbiota in health and disease.
Physiological reviews, 90 3
Y. Sjögren, M. Jenmalm, M. Böttcher, B. Björkstén, E. Sverremark-Ekström (2009)Altered early infant gut microbiota in children developing allergy up to 5 years of age
Clinical & Experimental Allergy, 39
T. Ball, J. Castro-Rodriguez, Kent Griffith, C. Holberg, F. Martinez, A. Wright (2000)Siblings, day-care attendance, and the risk of asthma and wheezing during childhood.
The New England journal of medicine, 343 8
A. Linneberg, C. Ostergaard, M. Tvede, L. Andersen, N. Nielsen, F. Madsen, L. Frølund, A. Dirksen, T. Jørgensen (2003)IgG antibodies against microorganisms and atopic disease in Danish adults: the Copenhagen Allergy Study.
The Journal of allergy and clinical immunology, 111 4
P. Parronchi, M. Carli, Roberto Manetti, C. Simonelli, S. Sampognaro, M. Piccinni, D. Macchia, E. Maggi, G. Prete, S. Romagnani (1992)IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones.
Journal of immunology, 149 9
John Penders, E. Stobberingh, C. Thijs, Hanne Adams, Cornelis Vink, C. Reevan, A. BrandtvandenPiet (2006)Molecular fingerprinting of the intestinal microbiota of infants in whom atopic eczema was or was not developing
Clinical & Experimental Allergy, 36
S. Romagnani (2004)The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?
R. Inoue, Y. Sakaue, Chihiro Sawai, T. Sawai, Motoyuki Ozeki, G. Romero-Pérez, T. Tsukahara (2016)A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders
Bioscience, Biotechnology, and Biochemistry, 80
Lindsay Parnell, Catherine Briggs, B. Cao, Omar Delannoy-Bruno, Andrew Schrieffer, I. Mysorekar (2017)Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles
Scientific Reports, 7
N. Cattane, J. Richetto, A. Cattaneo (2020)Prenatal exposure to environmental insults and enhanced risk of developing Schizophrenia and Autism Spectrum Disorder: focus on biological pathways and epigenetic mechanisms
Neuroscience & Biobehavioral Reviews, 117
Alexander Carlson, K. Xia, M. Azcárate-Peril, Barbara Goldman, Mihye Ahn, M. Styner, Amanda Thompson, X. Geng, John Gilmore, Rebecca Knickmeyer (2018)Infant Gut Microbiome Associated With Cognitive Development
Biological Psychiatry, 83
(2015)This study shows that factors such as the gestational age and delivery mode strongly influence the acquisition of the early microbiota even in healthy neonates
H. Wopereis, K. Sim, A. Shaw, J. Warner, J. Knol, S. Kroll (2017)Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development
The Journal of Allergy and Clinical Immunology, 141
S. Eaton, M. Konner (1985)Paleolithic nutrition. A consideration of its nature and current implications.
The New England journal of medicine, 312 5
H. Groux, A. O’Garra, M. Bigler, M. Rouleau, S. Antonenko, J. Vries, M. Roncarolo (1997)A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
M. Franchini, P. Mannucci (2012)Air pollution and cardiovascular disease.
Thrombosis research, 129 3
M. Al-Asmakh, F. Anuar, F. Zadjali, J. Rafter, S. Pettersson (2012)Gut microbial communities modulating brain development and function
Gut Microbes, 3
A. Wold (1998)The hygiene hypotheslis revised: is the rising frequency of allergy due to changes in the intestinal flora?
S. Rautava, O. Ruuskanen, A. Ouwehand, S. Salminen, E. Isolauri (2004)The hygiene hypothesis of atopic disease--an extended version.
Journal of pediatric gastroenterology and nutrition, 38 4
X. Cong, M. Judge, Wanli Xu, Ana Diallo, Susan Janton, E. Brownell, K. Maas, J. Graf (2017)Influence of Feeding Type on Gut Microbiome Development in Hospitalized Preterm Infants
Nursing Research, 66
G. Rook, L. Brunet (2005)Microbes, immunoregulation, and the gut
O. Thompson-Chagoyán, Matteo Fallani, J. Maldonado, J. Vieites, S. Khanna, C. Edwards, J. Doré, Á. Gil (2011)Faecal Microbiota and Short-Chain Fatty Acid Levels in Faeces from Infants with Cow‘s Milk Protein Allergy
International Archives of Allergy and Immunology, 156
B. Björkstén (1999)Environment and infant immunity
Proceedings of the Nutrition Society, 58
J. Matson, Alison Kozlowski (2011)The increasing prevalence of autism spectrum disorders
Research in Autism Spectrum Disorders, 5
Masaru Tanaka, Yuki Korenori, M. Washio, Takako Kobayashi, Rie Momoda, C. Kiyohara, Aki Kuroda, Yuka Saito, K. Sonomoto, J. Nakayama (2017)Signatures in the gut microbiota of Japanese infants who developed food allergies in early childhood.
FEMS microbiology ecology, 93 8
S. Romagnani (2006)Regulation of the T cell response
Clinical & Experimental Allergy, 36
A. Kim (2015)Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease.
Journal of clinical gastroenterology, 49 Suppl 1
A. Cassidy-Bushrow, C. Burmeister, S. Havstad, A. Levin, S. Lynch, D. Ownby, A. Rundle, K. Woodcroft, E. Zoratti, C. Johnson, G. Wegienka (2018)Prenatal antimicrobial use and early-childhood body mass index
International Journal of Obesity, 42
R. Heijtz, Shugui Wang, F. Anuar, Y. Qian, B. Björkholm, Annika Samuelsson, M. Hibberd, H. Forssberg, S. Pettersson (2011)Normal gut microbiota modulates brain development and behavior
Proceedings of the National Academy of Sciences, 108
Anna Sandin, L. Bråbäck, E. Norin, B. Björkstén (2009)Faecal short chain fatty acid pattern and allergy in early childhood
Acta Pædiatrica, 98
B. Björkstén, E. Sepp, K. Julge, T. Voor, M. Mikelsaar (2001)Allergy development and the intestinal microflora during the first year of life.
The Journal of allergy and clinical immunology, 108 4
M. Gosalbes, Y. Vallès, Nuria Jimenéz-Hernandéz, Christina Balle, P. Riva, Samuel Miravet-Verde, L. Vries, S. Llop, Y. Agersø, S. Sørensen, F. Ballester, M. Francino (2015)High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples
Journal of Developmental Origins of Health and Disease, 7
M. Laursen, Louise Andersen, K. Michaelsen, C. Mølgaard, E. Trolle, M. Bahl, T. Licht (2016)Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity
K. Mah, Bengt Björkstén, B. Lee, H. Bever, L. Shek, T. Tan, Yuan-Kun Lee, Kaw Chua (2006)Distinct Pattern of Commensal Gut Microbiota in Toddlers with Eczema
International Archives of Allergy and Immunology, 140
M. Yazdanbakhsh, P. Kremsner, R. Ree (2002)Allergy, parasites, and the hygiene hypothesis.
Science, 296 5567
D. Strachan (1989)Hay fever, hygiene, and household size.
British Medical Journal, 299
(2015)This work is important as it not only shows that the early lack of certain GIT microbes and associated metabolites is associated with the risk of developing asthma, but, going further
B. Franklin, R. Brook, C. Pope (2015)Air pollution and cardiovascular disease.
Current problems in cardiology, 40 5
M. Böttcher, EK Nordin, Anna Sandin, Tore Midtvedt, Bengt Björkstén (2000)Microflora‐associated characteristics in faeces from allergic and nonallergic infants
Clinical & Experimental Allergy, 30
M. Perez-Muñoz, M. Arrieta, A. Ramer-Tait, J. Walter (2017)A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome
R. Ley, P. Turnbaugh, S. Klein, J. Gordon (2006)Microbial ecology: Human gut microbes associated with obesity
C. Watkins, C. Stanton, C. Ryan, R. Ross (2017)Microbial Therapeutics Designed for Infant Health
Frontiers in Nutrition, 4
M. Gosalbes, S. Llop, S. Llop, Y. Vallès, A. Moya, A. Moya, F. Ballester, F. Ballester, F. Ballester, M. Francino, M. Francino (2013)Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants
Clinical & Experimental Allergy, 43
E. Mutlu, P. Engen, S. Soberanes, D. Urich, C. Forsyth, R. Niğdelioğlu, S. Chiarella, K. Radigan, Angel Gonzalez, S. Jakate, A. Keshavarzian, G. Budinger, G. Mutlu (2011)Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice
Particle and Fibre Toxicology, 8
Bei Gao, L. Chi, R. Mahbub, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, Kun Lu (2017)Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.
Chemical research in toxicology, 30 4
Dae-Wook Kang, J. Adams, A. Gregory, A. Gregory, T. Borody, Lauren Chittick, Lauren Chittick, A. Fasano, A. Khoruts, Elizabeth Geis, J. Maldonado, Sharon McDonough-Means, Elena Pollard, Simon Roux, Simon Roux, M. Sadowsky, Karen Lipson, M. Sullivan, Matthew Sullivan, J. Caporaso, R. Krajmalnik-Brown (2017)Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study
E. Mutlu, I. Comba, Takugo Cho, P. Engen, Cemal Yazici, S. Soberanes, R. Hamanaka, R. Niğdelioğlu, A. Meliton, A. Ghio, G. Budinger, G. Mutlu (2018)Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome.
Environmental pollution, 240
M. Collado, E. Isolauri, K. Laitinen, S. Salminen (2010)Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy.
The American journal of clinical nutrition, 92 5
P. Wadhwa, C. Buss, S. Entringer, J. Swanson (2009)Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.
Seminars in reproductive medicine, 27 5
J. Bach (2002)The effect of infections on susceptibility to autoimmune and allergic diseases.
The New England journal of medicine, 347 12
K. Korpela, M. Zijlmans, M. Kuitunen, K. Kukkonen, Erkki Savilahti, Anne Salonen, C. Weerth, W. Vos, W. Vos (2017)Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use
M. Arrieta, Leah Stiemsma, P. Dimitriu, L. Thorson, Shannon Russell, Sophie Yurist-Doutsch, B. Kuzeljevic, Matthew Gold, Heidi Britton, D. Lefebvre, P. Subbarao, P. Mandhane, A. Becker, K. McNagny, M. Sears, T. Kollmann, Child Investigators, W. Mohn, S. Turvey, B. Finlay (2015)Early infancy microbial and metabolic alterations affect risk of childhood asthma
Science Translational Medicine, 7
T. Cerdó, Alicia Ruiz, R. Jáuregui, Hatim Azaryah, F. Torres-Espínola, L. García-Valdés, M. Segura, Antonio Suárez, C. Campoy (2018)Maternal obesity is associated with gut microbial metabolic potential in offspring during infancy
Journal of Physiology and Biochemistry, 74
R. Heijtz (2016)Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior.
Seminars in fetal & neonatal medicine, 21 6
P. Eckburg, E. Bik, C. Bernstein, E. Purdom, L. Dethlefsen, Michael Sargent, S. Gill, K. Nelson, D. Relman (2005)Diversity of the Human Intestinal Microbial Flora
Shivani Ghaisas, Joshua Maher, A. Kanthasamy (2016)Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases.
Pharmacology & therapeutics, 158
Y. Borre, G. O’Keeffe, G. Clarke, C. Stanton, T. Dinan, J. Cryan (2014)Microbiota and neurodevelopmental windows: implications for brain disorders.
Trends in molecular medicine, 20 9
L. Kish, N. Hotte, G. Kaplan, R. Vincent, R. Tso, Michael Gänzle, K. Rioux, A. Thiesen, H. Barkema, E. Wine, K. Madsen (2013)Environmental Particulate Matter Induces Murine Intestinal Inflammatory Responses and Alters the Gut Microbiome
PLoS ONE, 8
Mairi Noverr, G. Huffnagle (2005)The ‘microflora hypothesis’ of allergic diseases
Clinical & Experimental Allergy, 35
S. Gilbert (2014)A holobiont birth narrative: the epigenetic transmission of the human microbiome
Frontiers in Genetics, 5
F. Bäckhed, Hao Ding, Ting Wang, L. Hooper, G. Koh, A. Nagy, C. Semenkovich, J. Gordon (2004)The gut microbiota as an environmental factor that regulates fat storage.
Proceedings of the National Academy of Sciences of the United States of America, 101 44
M. Yazdanbakhsh, P. Matricardi (2004)Parasites and the hygiene hypothesis
Clinical Reviews in Allergy & Immunology, 26
M. Kalliomäki, M. Collado, S. Salminen, E. Isolauri (2008)Early differences in fecal microbiota composition in children may predict overweight.
The American journal of clinical nutrition, 87 3
T. Abrahamsson, Hedvig Jakobsson, Anders Andersson, Bengt Björkstén, Lars Engstrand, M. Jenmalm (2012)Low diversity of the gut microbiota in infants with atopic eczema.
The Journal of allergy and clinical immunology, 129 2
P. Turnbaugh, R. Ley, M. Mahowald, V. Magrini, E. Mardis, J. Gordon (2006)An obesity-associated gut microbiome with increased capacity for energy harvest
Hae-Jin Hu, Sin-Gi Park, H. Jang, Min-Gyu Choi, K. Park, J. Kang, Sang-Ick Park, Hye-Ja Lee, Seung-Hak Cho (2015)Obesity Alters the Microbial Community Profile in Korean Adolescents
PLoS ONE, 10
Xuechao Guo, Su Liu, Zhu Wang, Xu-xiang Zhang, Mei Li, Bing Wu (2014)Metagenomic profiles and antibiotic resistance genes in gut microbiota of mice exposed to arsenic and iron.
D. Barker (1997)Maternal nutrition, fetal nutrition, and disease in later life.
Nutrition, 13 9
Kyung Rhee, S. Phelan, J. McCaffery (2012)Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences
International Journal of Pediatrics, 2012
G. Hamra, N. Guha, A. Cohen, F. Laden, O. Raaschou-Nielsen, J. Samet, P. Vineis, F. Forastiere, P. Saldiva, T. Yorifuji, D. Loomis (2014)Outdoor Particulate Matter Exposure and Lung Cancer: A Systematic Review and Meta-Analysis
Environmental Health Perspectives, 122
T. Buie, D. Campbell, George Fuchs, G. Furuta, J. Levy, J. Vandewater, A. Whitaker, D. Atkins, M. Bauman, A. Beaudet, E. Carr, M. Gershon, S. Hyman, P. Jirapinyo, H. Jyonouchi, K. Kooros, R. Kushak, P. Levitt, S. Levy, Jeffery Lewis, Katherine Murray, M. Natowicz, A. Sabrá, B. Wershil, S. Weston, L. Zeltzer, H. Winter (2010)Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report
M. Wills-Karp, Joanna Santeliz, C. Karp (2001)The germless theory of allergic disease: revisiting the hygiene hypothesis
Nature Reviews Immunology, 1
Maggie Stanislawski, D. Dabelea, B. Wagner, M. Sontag, C. Lozupone, M. Eggesbø (2017)Pre-pregnancy weight, gestational weight gain, and the gut microbiota of mothers and their infants
Zhenmin Liu, N. Roy, Yanhong Guo, Hong-xin Jia, Leigh Ryan, L. Samuelsson, Ancy Thomas, J. Plowman, S. Clerens, L. Day, W. Young (2016)Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats.
The Journal of nutrition, 146 2
Purpose of Review We review how an altered microbiome in early life impacts on immune, metabolic, and neurological development, focusing on some of the most widespread diseases related to each of these processes, namely atopic disease, obesity, and autism. Recent Findings The early development of the microbial communities that inhabit the human body is currently challenged by factors that range from reduced exposure to microbes, antibiotic use, and poor dietary choices to widespread environmental pollution. Recent work has highlighted some of the long-term consequences that early alterations in the establishment of these microbiotas can have for different aspects of human development and health. Summary The long-term consequences of early microbiome alterations for human development and health are only beginning to be understood and will require in-depth investigation in the years to come. A solid understanding of how present day environ- mental conditions alter microbiome development, and of how an altered microbiome in early life impacts on life-long health, should inform both public health policies and the development of dietary and medical strategies to counteract early microbiota imbalances. . . . . . Keywords Gut microbiome Infant development Early programming Immune disease Obesity Autism spectrum disorder Introduction industrial revolution, the discovery of antibiotics, the creation of agri-business, and recently the elaboration and massive dis- Human evolution has been punctuated by precise moments tribution of processed foods . These changes appear to have throughout history associated to key changes in lifestyle: the had a profound effect on the evolution of human health and appearance of Homo sapiens sapiens, the shift from nomadic to disease. In the last century, such effects have likely included sedentary lifestyles with the introduction of agriculture, the the emergence and increased prevalence of allergies, asthma, and autoimmune diseases, with a concomitant decrease in the incidence of infectious diseases . In fact, Strachan in 1989 proposed the “hygiene hypothesis”, which stated that lack of exposure to microbes during early infancy was at the source of This article is part of the Topical Collection on Early Life Environmental the observed increased prevalence of allergy and asthma in Health westernized populations [3, 4]. Later on, the “Barker Hypothesis” (also called “Developmental Origins of Health * M. Pilar Francino and Disease (DOHaD)”) postulated that exposure to environ- email@example.com mental factors during both fetus development and immediately Department of Biological and Chemical Sciences, The University of after birth or nutritional deficiencies of the mother during ges- the West Indies, Cave Hill campus, Cave Hill, Barbados tation would result in an early programming for developing Unitat Mixta d’Investigació en Genòmica i Salut, Fundació per al cardiovascular, neurodevelopmental, and metabolic disorders Foment de la Investigació Sanitària i Biomèdica de la Comunitat [5–8]. The latter hypotheses emphasize the notion that infancy Valenciana (FISABIO-Salut Pública)/Institut de Biologia Integrativa is likely to be a critical stage in human development in which de Sistemes (Universitat de València), Avda. Catalunya 21, 46020 València, Spain interventions could potentially prevent or decrease risk factors of latent disorders. Interestingly, there is growing evidence that CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain early microbiome-host interactions during fetus development Curr Envir Health Rpt (2018) 5:512–521 513 and early infancy are critical factors that will determine life- early onset of type 2 diabetes , and, in the latter case, the long health or disease states [9–11]. However, although it is dendritic cells of the immune system have been implicated in clear that the first months of life represent a crucial time win- mediating the increased translocation level. The proposition dow in the establishment of microbiome-host interactions, the that maternal bacteria reach the fetal gut is ground breaking, as precise boundaries of this window and the impact of microbial these organisms could start marking the trajectories of im- changes during later periods of infancy and childhood on life- mune, metabolic, and somatic development in utero, with long disease risks remain to be determined. enormous implications for the health of the individual . Complex endeavors such as those undertaken by the Here, we review several aspects of human development and Human Microbiome Project and the MetaHit Consortium health that are known to be affected by the gut microbiome in have been key in highlighting the significance and complexity early life, as well as the emergent evidence for air pollution as a of the microbiota inhabiting the niches provided by the human hitherto rarely considered environmental factor that likely contrib- body. It is now well accepted that the human’s gastrointestinal utes to altering the establishment of the gut microbiome (Fig. 1). tract (GIT) gathers the most diverse and dense microbiota of the human body, which in turn plays fundamental roles in gut homeostasis [12, 13]. Supporting the hygiene and Barker hy- Air Pollution: an Environmental Factor potheses, there is now a great body of knowledge establishing Recently Associated to Microbiome Dysbiosis that GIT microbiota composition during infancy and child- hood are associated to an incredible array of human diseases, Air pollution is the presence of harmful substances in the air from GIT-related diseases (i.e., metabolic disorders such as that can result from natural causes (i.e., volcano eruptions, diabetes and obesity, inflammatory bowel disease), to immune wind dust) and human activities (i.e., combustion of fuels, diseases and neurological disorders [14–22]. industry, traffic, cooking, smoking). The presence in polluted The advent of sequencing technologies that enable the deep air of larger proportions of CO ,SO , other toxic gases, chem- 2 2 characterization of microbial communities without the need ical compounds, and different sizes of particulate matter (PM) for isolation and culturing of their individual members has constitutes a universal hazard to those organisms exposed to it. revealed the great complexity of the human microbiome, as In fact, correlations of long-term exposures to air pollution well as the presence of rare or unculturable organisms that had and mortality have been addressed in several cohort-based previously escaped detection. Interestingly, these advances studies in different parts of the world [34, 35]. They have have not only led to the discovery of the importance and demonstrated the existence of an association between long- involvement in health and disease of the human microbiome, term exposure to fine PM and an increased risk of cardiovas- but also to surprising breakthroughs challenging long- cular and lung disease, as well as increased risk of lung cancer standing dogmas. In particular, until recently, it was believed . It has also been suggested that air pollution is associated that in health, the placenta was an impenetrable barrier to to gastrointestinal disorders by being potentially involved in bacteria maintaining an in utero sterile environment in which the pathophysiology of inflammatory bowel disease . the fetus developed. However, numerous recent analyses Air pollutants are inhaled into the lungs. The smaller parti- based on the amplification and high-throughput sequencing cles can reach the alveolar space where they can be phagocy- of bacterial 16S-rRNA genes have demonstrated the presence tosed by alveolar macrophages and consequently transported to of bacteria in the placenta [23–25], umbilical cord , am- the oropharynx and into the GIT . In addition, air pollutants niotic fluid , and meconium [27–29]. Moreover, experi- can also enter the body through the oral cavity being directly mental work has confirmed an efflux of bacteria from the ingested with food and liquids in significant amounts. Mutlu mother’s gut to that of the fetus, as genetically labeled bacteria et al. (2011) demonstrated that exposure to PM increased the orally inoculated to pregnant mice are recovered from the production of mitochondrial reactive oxygen species (ROS) meconium of offspring obtained by C-section . and the release of inflammatory cytokines among other effects, Following the latter, several hypotheses have been proposed increasing overall gut permeability . Thelatterinturncan as to how bacteria can reach in health the in utero environ- potentially affect the dynamics of the gut microbiota, possibly ment, including entry into the mother’s bloodstream via trans- resulting in imbalances of this community. A recent study in location events from the mother’s GIT and the oral cavity [23, which mice were exposed to ambient PM (PM with a diam- 2.5 24, 30]. The important physiological changes occurring in the eter of 2.5 μm or less), during 8 h a day, showed that there were GIT during pregnancy and in particular during the third tri- significant changes in the mice GIT microbial diversity and mester entail an inflammatory state of the intestinal epitheli- composition. Interestingly, there was a significant increase of um, similar to that present in obesity and diabetes , which the family S24_7 (order Bacteroidales), whose members have could enhance translocation events of bacteria. In fact, in high host glycan degradation potential, likely being involved in mice, enhanced bacterial translocation from the gut has been the degradation of the mucus layer and therefore increasing GIT shown to take place both during late pregnancy  and at the permeability . Also, the proportions of Firmicutes were 514 Curr Envir Health Rpt (2018) 5:512–521 Fig. 1 Air pollution, among many other factors, may alter the balance of the gut microbiota and contribute to altered immune, metabolic, and neurological development significantly depleted, which could be accounted for, among Although human studies are still lacking, the results obtain- other reasons, by the observed disappearance of the genus ed in animal models, together with the widespread occurrence Lactobacillus, traditionally considered as a beneficial commen- of air pollution in present day cities, raise the possibility that sal promoting GIT homeostasis . This depletion of this environmental factor is contributing significantly to Firmicutes has been correlated in other studies to an inflamma- microbiome-related health issues. Beyond metals and partic- tory state of the GIT. ular matter, numerous toxic gases and other chemical com- In 2013,Kishetal. showed that mice exposedbyoralin- pounds that can be present in polluted air could also have gestion to PM from Ottawa’s urban environment, during a important effects on the gut microbiota, but, to date, their period of 7–14 days, presented an altered gut microbiota com- potential roles in contributing to gut dysbioses associated with position and function and exhibited an acute and chronic in- modern urban life have yet to be studied. The fact that air flammatory response in the intestine . Exposure of mice to pollution is associated to increased permeability and inflam- heavy metals administered through drinking water, such as lead mation of the GIT  likely has an important impact on (10ppm for13weeks [41� ]or 100–500 ppm for 8 weeks ), pregnant women exposed to it, as it could exacerbate undesir- arsenic (10 or 250 ppm for periods of 2, 5, and 10 weeks or able bacterial translocation events through the gut barrier, set- −1 −1 3mg L for 90 days ), and iron (5 mg L for 90 days ting the stage for an imbalance in the types of bacteria that ), whether independently or in a combination of arsenic and may reach the fetal gut and seed the infant’smicrobiota. iron , resulted in changes of the relative abundances of taxa when comparing controls to exposed groups, as well as changes in metabolic functions. For example, in those mice exposed to Immune Health: Atopic Disease arsenic and/or iron, an increased prevalence of antibiotic resis- tance genes was observed, implying a fitness advantage for those The microbiota of the gut develops in close interaction with bacteria that possess them and increasing the potential for path- immune development in a process that can shape the main de- ogens to acquire them as well through horizontal gene transfer. terminants of life-long propensity to immune disease. Innate Curr Envir Health Rpt (2018) 5:512–521 515 immunity is most developed in the intestinal tract, where both products, such as short-chain fatty acids, have also been asso- immune and epithelial cells encode a variety of receptors for ciated with food allergies [76, 77], confirming that the metabol- ligands of microbial origin [45, 46]. Engagement of these recep- ic output of the microbiota is relevant for atopy development. tors results in the production of cytokines that will direct the differentiation of the naïve T cells of the adaptive immune sys- tem. These cells can differentiate into regulatory cells (Tregs) or into helper cells, such as Th1, Th2, and Th17 [46, 47]. The Metabolic Disorders: Obesity activity of Tregs results in a variety of anti-inflammatory roles and suppresses the activation and development of other naïve T Obesity, or excessive body fat accumulation, is a complex cells towards Th types [47–49]. The different Th cells play spe- disease characterized by a low-grade systemic inflammatory cific roles in shaping the immune response [47, 50, 51]and tone that is influenced by genetic, environmental, and lifestyle produce cytokines that suppress other Th types [52, 53]. Thus, factors. Obesity has become in the past few decades one of the an aberrant microbial colonization can produce an imbalance major public health concerns worldwide, as its prevalence has among the different types of T cells, and the consequent immune increased at an alarming rate in adults and what is more deregulation can generate a variety of pathological outcomes, disturbing, in children, particularly in urban settings of low- ranging from atopy to autoimmune disease [9–11, 54–58]. and middle-income countries . In fact, the World Health In support of this notion, it has long been known that a Organization (WHO) reported that the number of overweight reduced exposure to microbes increases the likelihood of dis- children under the age of 5 was estimated in 2013 to be over eases related to immune imbalances . For instance, infants 42 million worldwide . These facts are unsettling as that have higher numbers of siblings, that co-inhabit with overweight/obese children are likely to remain overweight/ household pets, that attend group day care at an earlier age, or obese when adults and are more prone to develop non- that live in farms have a much lower incidence of atopic dis- communicable diseases like diabetes and cardiovascular dis- ease, presumably mediated by their higher exposure to mi- orders at a younger age [78, 79]. crobes [4, 59–61]. Nowadays, a large number of studies have One of the main functions of the GIT microbiota is the been able to demonstrate associations between gut microbiota extraction of energy from otherwise indigestible dietary composition during infancy and early childhood and a variety polysaccharides, which can be used or stored in adipocytes of atopic diseases [9, 10, 45, 58, 62–68, 69]. In particular, a [80, 81]. In fact, Bäckhed et al. in 2004 were able to show deficiency in bifidobacteria has often been linked to increased that germ-free (GF) mice accumulated less fat than wild-type risks of atopy, although two large prospective studies could not mice and that introducing gut microbiota into the GF mice confirm such an association [68, 70]. Discrepancies may arise resulted in an increase of body fat accumulation despite a from the fact that different human populations will have distinct low-calorie intake diet . genetic backgrounds and may carry different bacterial species The GIT’s microbiome in healthy individuals is character- and strains of Bifidobacterium. More recently, a large analysis ized by a highly diverse taxonomic composition where most of of the gut microbiota of children enrolled in the Canadian the organisms pertain to five major phyla: Firmicutes, Healthy Infant Longitudinal Development (CHILD) Study Bacteroidetes, Actinobacteria, Proteobacteria, and has shown that infants at risk of asthma had a lower abundance Fusobacteria . While obesity has been linked in multiple of the Firmicutes genera Lachnospira, Veillonella, studies comparing lean and obese individuals with changes in Faecalibacterium,and Rothia, accompanied by decreased the abundance ratio between Firmicutes and Bacteroidetes, con- levels of fecal acetate and dysregulation of enterohepatic me- flicting results have been reported as well [80, 81, 84–86]. What tabolites. Importantly, the inoculation of germ-free mice with is well established is that obesity is related to a decrease in these four bacteria ameliorated airway inflammation, demon- microbial diversity in general and that this phenotype predis- strating their causal role in preventing asthma . On the poses the individuals to further inflammation . other hand, increased abundances of Clostridium and of the The prevalence of obesity among women in age of repro- enteric bacteria have also been associated with atopic disease duction worldwide has considerably increased in the past few [58, 62, 64–67, 71–75], as well as an overall decrease in the decades and with it the predisposition of their infants to also diversity of the infants’ GIT microbiota [62, 67]. Moreover, a develop obesity during childhood [88, 89]. The latter can be study of meconium samples from the INMA cohort has shown due to inheritance of obesity susceptibility genes and/or expo- that the association of low diversity and high levels of enteric sure to high-calorie diets but also, as noted above, to the pres- bacteria with atopic disease may be initiated by maternal factors ence of an aberrant GIT microbiota. Since initial colonization in utero . In this work, these compositional patterns were of the infant’s GIT starts in utero and may involve bacteria already detected in the meconium of children who developed deriving from the mother’s GIT, we expect that the infant’s eczema by 4 years of age or whose mothers had a history of GIT will be influenced by the mother’s condition, presenting from birth an anomalous microbial community. eczema. Finally, the fecal levels of bacterial fermentation �� �� 516 Curr Envir Health Rpt (2018) 5:512–521 Multiple studies have addressed this question. Among them, continues after birth, being continuously influenced by cue Collado et al. (2010) looked at the GIT’s microbiota composi- signals from the environment. The latter can have, later on, a tion in infants at 1 and 6 months of age, finding that at 6 months, profound impact on brain and behavior development during there was a correlation between microbiota composition and the early childhood, in line with the “Barker’shypothesis” . It obesity status of the mother . In contrast, Laursen and col- is well accepted that normal development of the fetus brain leagues (2016) found no association between the mother’sbody while in utero requires a specific balance of cytokines in both mass index (BMI) and the infant’s gut microbiota . the maternal and fetal environments . Stanislawski et al. (2017) explored whether pre-pregnancy Remarkably, an association has been found between ASD overweight/obesity and gestational weight gain were associated and the prevalence of gastrointestinal disorders . In ad- to different gut microbial communities at the time of delivery as dition, recent work has demonstrated that the composition and well as with the infants’ gut microbiotas. They found that al- diversity of the gut microbiome, which, as discussed above, though the maternal gut microbiota composition was associated plays a key role in the modulation of immune system re- to their overweight/obese and gestational weight gain status, sponses (i.e., cytokine and neurotransmitter secretion), are there was only a weak association to their infants’ gut microbi- significantly associated with cognition and neurological dis- ota composition . Yet, Cerdó et al. (2018) found that the orders such as ASD in human infants and children [20, mother’s pre-pregnancy BMI status was actually associated to 104–106]. In fact, epidemiological studies and experimental the functional profile of the infant’s microbial community, sug- work with mice have revealed a direct link between microbial gesting a possible role of maternal imprinting in the selection of pathogen infections during the prenatal phase and post-natal gut microbial communities with specific functional potentials development of autism and behavioral abnormalities, respec- . In spite of the inconclusive results observed in the latter tively [7, 107]. Moreover, Diaz Heijtz et al. (2011) found that studies, it is important to remember that the initial stages of an GF mice displayed higher motor activity and less anxiety infant’s gut microbiota establishment are hectic and dramatic when compared to mice with a normal gut microbiota (SPF) changes can occur in short lapses of time, thus complicating the and showed that GF mice inoculated early on with SPF mi- possibility of finding reliable associations . Moreover, crobiota displayed motor abilities and anxiety levels similar to many additional variables can confound association analyses normal SPF mice. Although only males were used in this due to their effects on the infant’s microbiota composition, such study, the integration of measurements of motor activity, as the mode of birth, milk supply (breastfeeding versus formu- anxiety-like behavior, neurochemical analysis, and gene ex- la), solid food introduction, exposure to antibiotics (strength, pression, among others, strengthens the results observed, duration, and number of doses), and exposure to the surround- linking the GIT microbiota to the gut-brain axis . ing environment [15, 93–95, 96� , 97, 98]. Furthermore, based on the fact that epidemiological studies have demonstrated the association between maternal infection On the other hand, the relevance of early life gut microbiota for the development of obesity has been clearly demonstrated. and increased autism risk in the offspring, Hsiao et al. (2013) Several analyses have shown that infants with a higher abun- showed that injecting pregnant mice of the Maternal Immune dance of Bifidobacterium during the first year of life have lower Activation (MIA) model with the viral mimic polyinosinic/ adiposity levels, BMI, and obesity risk at later ages, ranging polycytidylic acid (poly(I/C)), a synthetic double-stranded im- from 18 months to 7 years [96� , 99, 100]. These studies dem- mune-stimulant, resulted in offspring exhibiting characteristic onstrate that dysbiosis of the GIT’s microbiota does precede the symptoms of ASD (i.e., communicative and social onset of obesity. Interestingly, one of these studies revealed that impairments) and defects of intestinal barrier integrity . the influence exerted by the abundance of Bifidobacterium and In addition, MIA offspring presented a similar microbial other taxa on BMI appeared to be especially strong among composition to that observed in humans affected by ASD children with a history of antibiotic use . which was significantly different from offspring controls, with differences driven mostly by changes in the diversity of members of the Clostridia and Bacteroidia classes. More Neurological Disorders: Autism importantly, treatment of the MIA offspring with inoculations of Bacteroides fragilis corrected intestinal barrier integrity and Autism spectrum disorders (ASD) are an array of attenuated the abnormal communicative and social behaviors neurodevelopmental disorders characterized mainly by defi- observed . These findings and the fact that ASD shares ciencies in social behavior and communication skills, the many symptoms with many other neuropathophysiological prevalence of which has dramatically risen in the past few disorders are encouraging as they show the potential of decades . Initially believed to be a consequence only of developing therapies by modulation of the gut microbiome as a environmental exposures, there is now enough evidence that a safe and effective way of treatment. strong neurodevelopmental component is also at play . More recently, Kang et al. (2017) demonstrated that microbi- ota transfer therapy (MTT) with a standardized human gut Brain development in mammals starts early in utero and Curr Envir Health Rpt (2018) 5:512–521 517 microbiota, after 14 days of vancomycin treatment followed by adolescence, and the subsequent health effects, have received to 12–24-h fasting with bowel cleansing, was able to alter the gut date little attention. On the other hand, microbiotas other than microbiome and virome of children with ASD and to improve the one present in the gut have been comparatively neglected in GIT and behavioral symptoms, whether administered orally or terms of understanding their development and the potential ef- rectally [109 ]. More importantly, the improvements lasted for fects of early life alterations on later health and should be further 8 weeks after the end of treatment, suggesting a long-term im- investigated in this respect. Ideally, the establishment of lasting pact, and indicating that MTT could be a promising approach to longitudinal birth cohorts should be promoted, so that the eval- treat ASD. Despite these promising results, it is important to take uation of microbiome-related outcomes can be extended into into account that the number of participants included in the study adulthood. Such long-term projects should aim at gathering a was low and that patients were not necessarily homogeneous in wide scope of medical and environmental metadata, as well as the GI symptoms that they presented. In addition, the use of samples enabling the study of bacterial communities in a variety placebo controls would have strengthened the results obtained. of body sites, including, beyond the GIT, the oral cavity, respi- Environmental factors like air pollution might trigger or ratory system, skin, and urogenital tract. In particular, it is clear exacerbate ASD by impacting the gut microbiota, which in that environmental factors such as air pollution and exposure to dysbiosis potentially leads to an increased gut barrier perme- chemical contaminants present in food and water have received ability, increasing in turn bacterial translocation events and little attention in spite of their strong potential to impinge on potential leakage of other pathogens and compounds (antigens microbiome development and associated health outcomes. and bacterial metabolites) that can induce inflammatory re- On the positive side, the same malleability that renders early sponses and indirectly impinge on brain functions. microbiome development susceptible to negative alterations should make it responsive to strategic interventions aimed at modulating the microbiome to promote health. Research on early Conclusions microbiome development and on the effects of present day life conditions on this critical process will enable novel approaches in In the upcoming years, further efforts should focus on delineating public health, nutrition, and medicine that ensure the establish- the variety of long-term health outcomes that can result from or ment of a health-promoting microbiota. Such approaches will be aggravated by an unbalanced microbiota development. likely include the development of preventive or therapeutic treat- Because we now know that there are fetal microbial GIT com- ments based on the early administration of beneficial bacteria and munities, further research should better define how and when of nutritional supplements capable of promoting their growth. such communities are formed and to which extent they are capa- ble of influencing human development and disease risk during Compliance with Ethical Standards gestation. In this respect, it is also crucial to invest research efforts Conflict of Interest The authors declare that they have no conflicts of in understanding the health and environmental factors that shape interest. the maternal microbiome during pregnancy and how these affect the types of bacteria that reach the fetus. Regarding timing and Human and Animal Rights and Informed Consent This is a review mode of birth, although it is well established that these factors article and does not report any unpublished work with human or animal have a strong effect on early microbiome development, much subjects performed by any of the authors. research remains to be done in order to elucidate the specific Open Access This article is distributed under the terms of the Creative mechanisms through which these early events impinge on the Commons Attribution 4.0 International License (http:// establishment of microbiome-host interactions, at the immune, creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appro- metabolic, and neurodevelopmental level. Further, it will also be priate credit to the original author(s) and the source, provide a link to the necessary to delineate the post-natal time window during which Creative Commons license, and indicate if changes were made. the main traits of such microbiome-host interactions are defined, as this will be the critical period in which any preventative or therapeutic interventions aimed at modulating the microbiome References should be most effective. In addition, it will be important to investigate whether this time window is altered by the many Papers of particular interest, published recently, have been variables that affect the course and pace of microbiome develop- highlighted as: ment during the first months of life, such as type of milk feeding, � Of importance solid food introduction, exposure to antibiotics, and the many �� Of major importance environmental and lifestyle factors that shape infant exposure to microbes [15, 93–98]. 1. Eaton SB, Konner M. Paleolithic nutrition. A consideration of its Beyond infancy, the extent to which microbiome composi- nature and current implications. N Engl J Med. 1985;312(5):283– tion may be altered by different factors during childhood and 9. https://doi.org/10.1056/NEJM198501313120505. �� 518 Curr Envir Health Rpt (2018) 5:512–521 2. Bach JF. The effect of infections on susceptibility to autoimmune 21. Diaz HR. Fetal, neonatal, and infant microbiome: perturbations and subsequent effects on brain development and behavior. and allergic diseases. N Engl J Med. 2002;347(12):911–20. https://doi.org/10.1056/NEJMra020100. Semin Fetal Neonatal Med. 2016;21(6):410–7. https://doi.org/ 10.1016/j.siny.2016.04.012. 3. Strachan DP. Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax. 2000;55(Suppl 1):S2–10. 22. Borre YE, O'Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota and neurodevelopmental windows: implications 4. Strachan DP. Hay fever, hygiene, and household size. BMJ. for brain disorders. Trends Mol Med. 2014;20(9):509–18. 1989;299(6710):1259–60. https://doi.org/10.1016/j.molmed.2014.05.002. 5. Wadhwa PD, Buss C, Entringer S, Swanson JM. Developmental 23. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med. The placenta harbors a unique microbiome. Sci Transl Med. 2009;27(5):358–68. https://doi.org/10.1055/s-0029-1237424. 2014;6(237):237ra65. https://doi.org/10.1126/scitranslmed. 6. Swanson JM, Entringer S, Buss C, Wadhwa PD. Developmental 3008599. origins of health and disease: environmental exposures. Semin 24. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial Reprod Med. 2009;27(5):391–402. https://doi.org/10.1055/s- 0029-1237427. communities in the placenta and amniotic fluid. Sci Rep. 2016;6: 23129. https://doi.org/10.1038/srep23129. 7. Al-Asmakh M, Anuar F, Zadjali F, Rafter J, Pettersson S. Gut microbial communities modulating brain development and func- 25. Parnell LA, Briggs CM, Cao B, Delannoy-Bruno O, Schrieffer tion. Gut Microbes. 2012;3(4):366–73. https://doi.org/10.4161/ AE, Mysorekar IU. Microbial communities in placentas from term gmic.21287. normal pregnancy exhibit spatially variable profiles. Sci Rep. 8. Barker DJ. Maternal nutrition, fetal nutrition, and disease in later 2017;7(1):11200. https://doi.org/10.1038/s41598-017-11514-4. life. Nutrition. 1997;13(9):807–13. 26. Jimenez E, Fernandez L, Marin ML, Martin R, Odriozola JM, 9. Wold AE. The hygiene hypothesis revised: is the rising frequency Nueno-Palop C, et al. Isolation of commensal bacteria from um- of allergy due to changes in the intestinal flora? Allergy. bilical cord blood of healthy neonates born by cesarean section. 1998;53(46 Suppl):20–5. Curr Microbiol. 2005;51(4):270–4. https://doi.org/10.1007/ 10. Bjorksten B. Environment and infant immunity. Proc Nutr Soc. s00284-005-0020-3. 27. Jimenez E, Marin ML, Martin R, Odriozola JM, Olivares M, Xaus 1999;58(3):729–32. J, et al. Is meconium from healthy newborns actually sterile? Res 11. Noverr MC, Huffnagle GB. The 'microflora hypothesis' of allergic Microbiol. 2008;159(3):187–93. https://doi.org/10.1016/j.resmic. diseases. Clin Exp Allergy. 2005;35(12):1511–20. https://doi.org/ 10.1111/j.1365-2222.2005.02379.x. 2007.12.007. 28. Gosalbes MJ, Llop S, Valles Y, Moya A, Ballester F, Francino MP. 12. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in Meconium microbiota types dominated by lactic acid or enteric health and disease. Physiol Rev. 2010;90(3):859–904. https://doi. org/10.1152/physrev.00045.2009. bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy. 2013;43(2): 13. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. 198–211. https://doi.org/10.1111/cea.12063. 29. Gosalbes MJ, Valles Y, Jimenez-Hernandez N, Balle C, Riva P, https://doi.org/10.1038/nature11234. Miravet-Verde S, et al. High frequencies of antibiotic resistance 14. Watkins C, Stanton C, Ryan CA, Ross RP. Microbial therapeutics genes in infants' meconium and early fecal samples. J Dev Orig designed for infant health. Front Nutr. 2017;4:48. https://doi.org/ Health Dis. 2016;7(1):35–44. https://doi.org/10.1017/ 10.3389/fnut.2017.00048. S2040174415001506. 15. Cassidy-Bushrow AE, Burmeister C, Havstad S, Levin AM, 30. Perez-Munoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A crit- Lynch SV, Ownby DR, et al. Prenatal antimicrobial use and early-childhood body mass index. Int J Obes. 2018;42(1):1–7. ical assessment of the "sterile womb" and "in utero colonization" https://doi.org/10.1038/ijo.2017.205. hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017;5(1):48. https://doi.org/10.1186/ 16. Cerdo T, Ruiz A, Jauregui R, Azaryah H, Torres-Espinola FJ, Garcia-Valdes L, et al. Maternal obesity is associated with gut s40168-017-0268-4. 31. Gilbert SF. A holobiont birth narrative: the epigenetic transmission microbial metabolic potential in offspring during infancy. J Physiol Biochem. 2018;74(1):159–69. https://doi.org/10.1007/ of the human microbiome. Front Genet. 2014;5:282. https://doi. s13105-017-0577-x. org/10.3389/fgene.2014.00282. 32. Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, 17. Mulligan CM, Friedman JE. Maternal modifiers of the infant gut microbiota: metabolic consequences. J Endocrinol. 2017;235(1): et al. Bacterial imprinting of the neonatal immune system: lessons R1–R12. https://doi.org/10.1530/JOE-17-0303. from maternal cells? Pediatrics. 2007;119(3):e724–32. https://doi. 18. Tanaka M, Korenori Y, Washio M, Kobayashi T, Momoda R, org/10.1542/peds.2006-1649. Kiyohara C et al. Signatures in the gut microbiota of Japanese 33. Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez- Humaran LG, et al. Intestinal mucosal adherence and translocation infants who developed food allergies in early childhood. FEMS Microbiol Ecol. 2017;93(8). doi:https://doi.org/10.1093/femsec/ of commensal bacteria at the early onset of type 2 diabetes: mo- fix099. lecular mechanisms and probiotic treatment. EMBO Mol Med. 19. Wopereis H, Sim K, Shaw A, Warner JO, Knol J, Kroll JS. 2011;3(9):559–72. https://doi.org/10.1002/emmm.201100159. In testinal microbiota in infants at high risk for allergy: effects of 34. Franklin BA, Brook R, Arden Pope C 3rd. Air pollution and car- prebiotics and role in eczema development. J Allergy Clin diovascular disease. Curr Probl Cardiol. 2015;40(5):207–38. https://doi.org/10.1016/j.cpcardiol.2015.01.003. Immunol. 2017;141:1334–1342.e5. https://doi.org/10.1016/j.jaci. 2017.05.054. 35. Lee WH, Choo JY, Son JY, Kim H. Association between long- term exposure to air pollutants and prevalence of cardiovascular 20. Inoue R, Sakaue Y, Sawai C, Sawai T, Ozeki M, Romero-Perez disease in 108 south Korean communities in 2008-2010: a cross- GA, et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear sectional study. Sci Total Environ. 2016;565:271–8. https://doi. org/10.1016/j.scitotenv.2016.03.163. cells of infants with autism spectrum disorders. Biosci Biotechnol Biochem. 2016;80(12):2450–8. https://doi.org/10.1080/ 36. Hamra GB, Guha N, Cohen A, Laden F, Raaschou-Nielsen O, 09168451.2016.1222267. Samet JM, et al. Outdoor particulate matter exposure and lung Curr Envir Health Rpt (2018) 5:512–521 519 cancer: a systematic review and meta-analysis. Environ Health capacity that produce transforming growth factor beta and inter- leukin-10. Clin Diagn Lab Immunol. 2001;8(4):695–701. https:// Perspect. 2014;122(9):906–11. https://doi.org/10.1289/ehp. 1408092. doi.org/10.1128/CDLI.8.4.695-701.2001. 37. Kaplan GG, Hubbard J, Korzenik J, Sands BE, Panaccione R, 52. Parronchi P, De Carli M, Manetti R, Simonelli C, Sampognaro S, Ghosh S, et al. The inflammatory bowel diseases and ambient Piccinni MP, et al. IL-4 and IFN (alpha and gamma) exert opposite air pollution: a novel association. Am J Gastroenterol. regulatory effects on the development of cytolytic potential by 2010;105(11):2412–9. https://doi.org/10.1038/ajg.2010.252. Th1 or Th2 human T cell clones. J Immunol. 1992;149(9):2977– 38. Mutlu EA, Engen PA, Soberanes S, Urich D, Forsyth CB, 83. 53. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN-gamma in Nigdelioglu R, et al. Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. Part immune regulation. I. IFN-gamma inhibits the proliferation of Th2 Fibre Toxicol. 2011;8:19. https://doi.org/10.1186/1743-8977-8- but not Th1 murine helper T lymphocyte clones. J Immunol. 19. 1988;140(12):4245–52. 39. Mutlu EA, Comba IY, Cho T, Engen PA, Yazici C, Soberanes S, 54. Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, et al. Inhalational exposure to particulate matter air pollution alters and the hygiene hypothesis. Science. 2002;296(5567):490–4. the composition of the gut microbiome. Environ Pollut. 2018;240: https://doi.org/10.1126/science.296.5567.490. 817–30. https://doi.org/10.1016/j.envpol.2018.04.130. 55. Wills-Karp M, Santeliz J, Karp CL. The germless theory of aller- 40. Kish L, Hotte N, Kaplan GG, Vincent R, Tso R, Ganzle M, et al. gic disease: revisiting the hygiene hypothesis. Nat Rev Immunol. Environmental particulate matter induces murine intestinal inflam- 2001;1(1):69–75. https://doi.org/10.1038/35095579. matory responses and alters the gut microbiome. PLoS One. 56. Rook GA, Brunet LR. Microbes, immunoregulation, and the gut. 2013;8(4):e62220. https://doi.org/10.1371/journal.pone.0062220. Gut. 2005;54(3):317–20. https://doi.org/10.1136/gut.2004. 41.� Gao B, Chi L, Mahbub R, Bian X, Tu P, Ru H, et al. Multi-omics 053785. reveals that Lead exposure disturbs gut microbiome development, 57. Rautava S, Ruuskanen O, Ouwehand A, Salminen S, Isolauri E. key metabolites, and metabolic pathways. Chem Res Toxicol. The hygiene hypothesis of atopic disease–an extended version. J 2017;30(4):996–1005. This study shows that environmental Pediatr Gastroenterol Nutr. 2004;38(4):378–88. exposures have an important impact not only on the structure 58. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, and diversity of the gut microbial community but also on its Stelma F, et al. Gut microbiota composition and development of metabolic functions leading to potential toxicity. https://doi.org/ atopic manifestations in infancy: the KOALA birth cohort study. 10.1021/acs.chemrestox.6b00401. Gut. 2007;56(5):661–7. https://doi.org/10.1136/gut.2006.100164. 42. Breton J, Massart S, Vandamme P, De Brandt E, Pot B, Foligne B. 59. von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Reitmeir P, Ecotoxicology inside the gut: impact of heavy metals on the Thiemann HH. Skin test reactivity and number of siblings. BMJ. mouse microbiome. BMC Pharmacol Toxicol. 2013;14:62. 1994;308(6930):692–5. https://doi.org/10.1186/2050-6511-14-62. 60. Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P. Cohort 43. Dheer R, Patterson J, Dudash M, Stachler EN, Bibby KJ, Stolz study of sibling effect, infectious diseases, and risk of atopic der- DB, et al. Arsenic induces structural and compositional colonic matitis during first 18 months of life. BMJ. 2004;328(7450):1223. microbiome change and promotes host nitrogen and amino acid https://doi.org/10.1136/bmj.38069.512245.FE. metabolism. Toxicol Appl Pharmacol. 2015;289(3):397–408. 61. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, https://doi.org/10.1016/j.taap.2015.10.020. Martinez FD, Wright AL. Siblings, day-care attendance, and the 44. Guo X, Liu S, Wang Z, Zhang XX, Li M, Wu B. Metagenomic risk of asthma and wheezing during childhood. N Engl J Med. profiles and antibiotic resistance genes in gut microbiota of mice 20 00;343(8):538 –43. https://doi.org/1 0.1056/ exposed to arsenic and iron. Chemosphere. 2014;112:1–8. https:// NEJM200008243430803. doi.org/10.1016/j.chemosphere.2014.03.068. 62. Wang M, Karlsson C, Olsson C, Adlerberth I, Wold AE, Strachan 45. Sjogren YM, Jenmalm MC, Bottcher MF, Bjorksten B, DP, et al. Reduced diversity in the early fecal microbiota of infants Sverremark-Ekstrom E. Altered early infant gut microbiota in with atopic eczema. J Allergy Clin Immunol. 2008;121(1):129– children developing allergyup to5 yearsof age.ClinExp 34. https://doi.org/10.1016/j.jaci.2007.09.011. Allergy. 2009;39(4):518–26. https://doi.org/10.1111/j.1365- 63. Kuvaeva IB, Orlova NG, Veselova OL, Kuznezova GG, Borovik 2222.2008.03156.x. TE. Microecology of the gastrointestinal tract and the immunolog- 46. Platt AM, Mowat AM. Mucosal macrophages and the regulation ical status under food allergy. Nahrung. 1984;28(6–7):689–93. of immune responses in the intestine. Immunol Lett. 2008;119(1– 64. Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, 2):22–31. https://doi.org/10.1016/j.imlet.2008.05.009. Isolauri E. Distinct patterns of neonatal gut microflora in infants 47. Romagnani S. Regulation of the T cell response. Clin Exp Allergy. in whom atopy was and was not developing. J Allergy Clin 2006;36(11):1357–66. https://doi.org/10.1111/j.1365-2222.2006. Immunol. 2001;107(1):129–34. https://doi.org/10.1067/mai. 02606.x. 2001.111237. 48. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de 65. Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy Vries JE, et al. A CD4+ T-cell subset inhibits antigen-specific T- development and the intestinal microflora during the first year of cell responses and prevents colitis. Nature. 1997;389(6652):737– life. J Allergy Clin Immunol. 2001;108(4):516–20. https://doi.org/ 42. https://doi.org/10.1038/39614. 10.1067/mai.2001.118130. 49. Romagnani S. The increased prevalence of allergy and the hygiene 66. Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan- hypothesis: missing immune deviation, reduced immune suppres- Muller G, et al. Reduced diversity of the intestinal microbiota sion, or both? Immunology. 2004;112(3):352–63. https://doi.org/ during infancy is associated with increased risk of allergic disease 10.1111/j.1365-2567.2004.01925.x. at school age. J Allergy Clin Immunol. 2011;128(3):646–52 e1–5. https://doi.org/10.1016/j.jaci.2011.04.060. 50. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition accord- 67. Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, ing to profiles of lymphokine activities and secreted proteins. J Engstrand L, Jenmalm MC. Low diversity of the gut microbiota Immunol. 1986;136(7):2348–57. in infants with atopic eczema. J Allergy Clin Immunol. 51. von der Weid T, Bulliard C, Schiffrin EJ. Induction by a lactic acid 2012;129(2):434–40, 40 e1–2. https://doi.org/10.1016/j.jaci. bacterium of a population of CD4(+) T cells with low proliferative 2011.10.025. 520 Curr Envir Health Rpt (2018) 5:512–521 68. Penders J, Stobberingh EE, Thijs C, Adams H, Vink C, van Ree R, 83. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, et al. Molecular fingerprinting of the intestinal microbiota of in- Sargent M, et al. Diversity of the human intestinal microbial flora. fants in whom atopic eczema was or was not developing. Clin Exp Science. 2005;308(5728):1635–8. https://doi.org/10.1126/ Allergy. 2006;36(12):1602–8. https://doi.org/10.1111/j.1365- science.1110591. 2222.2006.02599.x. 84. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: 69. Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, human gut microbes associated with obesity. Nature. Yurist-Doutsch S, et al. Early infancy microbial and metabolic 2006;444(7122):1022–3. https://doi.org/10.1038/4441022a. alterations affect risk of childhood asthma. Sci Transl Med. 85. Hu HJ, Park SG, Jang HB, Choi MK, Park KH, Kang JH, et al. 2015;7(307):307ra152. https://doi.org/10.1126/scitranslmed. Obesity alters the microbial community profile in Korean adoles- aab2271 This work is important as it not only shows that the cents. PLoS One. 2015;10(7):e0134333. https://doi.org/10.1371/ early lack of certain GIT microbes and associated metabolites journal.pone.0134333. is associated with the risk of developing asthma, but, going 86. Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis further, it also demonstrates in a mouse model that the P, et al. Human colonic microbiota associated with diet, obesity restoration of the missing protective microbes can prevent and weight loss. Int J Obes. 2008;32(11):1720–4. https://doi.org/ asthma development. 10.1038/ijo.2008.155. 70. Murray CS, Tannock GW, Simon MA, Harmsen HJ, Welling GW, 87. Kim A. Dysbiosis: a review highlighting obesity and inflammato- Custovic A, et al. Fecal microbiota in sensitized wheezy and non- ry bowel disease. J Clin Gastroenterol. 2015;49(Suppl 1):S20–4. sensitized non-wheezy children: a nested case-control study. Clin https://doi.org/10.1097/MCG.0000000000000356. Exp Allergy. 2005;35(6):741–5. https://doi.org/10.1111/j.1365- 88. Rhee KE, Phelan S, McCaffery J. Early determinants of obesity: 2222.2005.02259.x. genetic, epigenetic, and in utero influences. Int J Pediatr. 71. Woolcock AJ, Peat JK. Evidence for the increase in asthma world- 2012;2012:463850–9. https://doi.org/10.1155/2012/463850. wide. Ciba Found Symp. 1997;206:122–34 discussion 34–9, 57– 89. Herring SJ, Rose MZ, Skouteris H, Oken E. Optimizing weight gain in pregnancy to prevent obesity in women and children. 72. Mah KW, Bjorksten B, Lee BW, van Bever HP, Shek LP, Tan TN, Diabetes Obes Metab. 2012;14(3):195–203. https://doi.org/10. et al. Distinct pattern of commensal gut microbiota in toddlers with 1111/j.1463-1326.2011.01489.x. eczema. Int Arch Allergy Immunol. 2006;140(2):157–63. https:// 90. Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of doi.org/10.1159/000092555. mother's weight on infant's microbiota acquisition, composition, 73. Linneberg A, Ostergaard C, Tvede M, Andersen LP, Nielsen NH, and activity during early infancy: a prospective follow-up study Madsen F, et al. IgG antibodies against microorganisms and atopic initiated in early pregnancy. Am J Clin Nutr. 2010;92(5):1023–30. disease in Danish adults: the Copenhagen allergy study. J Allergy https://doi.org/10.3945/ajcn.2010.29877. Clin Immunol. 2003;111(4):847–53. 91. Laursen MF, Andersen LB, Michaelsen KF, Molgaard C, Trolle E, 74. Bottcher MF, Nordin EK, Sandin A, Midtvedt T, Bjorksten B. Bahl MI et al. Infant Gut Microbiota Development Is Driven by Microflora-associated characteristics in faeces from allergic and Transition to Family Foods Independent of Maternal Obesity. nonallergic infants. Clin Exp Allergy. 2000;30(11):1590–6. mSphere. 2016;1(1). doi:https://doi.org/10.1128/mSphere.00069- 75. Sepp E, Julge K, Mikelsaar M, Bjorksten B. Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children. 92. Stanislawski MA, Dabelea D, Wagner BD, Sontag MK, Lozupone Clin Exp Allergy. 2005;35(9):1141–6. https://doi.org/10.1111/j. CA, Eggesbo M. Pre-pregnancy weight, gestational weight gain, 1365-2222.2005.02315.x. and the gut microbiota of mothers and their infants. Microbiome. 76. Thompson-Chagoyan OC, Fallani M, Maldonado J, Vieites JM, 2017;5(1):113. https://doi.org/10.1186/s40168-017-0332-0. Khanna S, Edwards C, et al. Faecal microbiota and short-chain 93. Valles Y, Artacho A, Pascual-Garcia A, Ferrus ML, Gosalbes MJ, fatty acidlevels infaeces from infants with cow's milkprotein Abellan JJ, et al. Microbial succession in the gut: directional trends allergy. Int Arch Allergy Immunol. 2011;156(3):325–32. https:// of taxonomic and functional change in a birth cohort of Spanish doi.org/10.1159/000323893. infants. PLoS Genet. 2014;10(6):e1004406. https://doi.org/10. 77. Sandin A, Braback L, Norin E, Bjorksten B. Faecal short chain 1371/journal.pgen.1004406. fatty acid pattern and allergy in early childhood. Acta Paediatr. 94. Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, 2009;98(5):823–7. https://doi.org/10.1111/j.1651-2227.2008. Morrison HG, et al. Association of Cesarean Delivery and 01215.x. Formula Supplementation with the intestinal microbiome of 6- 78. WHO. Global status report on noncommunicable diseases2014. week-old infants. JAMA Pediatr. 2016;170(3):212–9. https://doi. 79. Leitner DR, Fruhbeck G, Yumuk V, Schindler K, Micic D, org/10.1001/jamapediatrics.2015.3732. Woodward E, et al. Obesity and type 2 diabetes: two diseases with 95. Liu Z, Roy NC, Guo Y, Jia H, Ryan L, Samuelsson L, et al. a need for combined treatment strategies - EASO can Lead the Human breast Milk and infant formulas differentially modify the way. Obes Facts. 2017;10(5):483–92. https://doi.org/10.1159/ intestinal microbiota in human infants and host physiology in rats. J Nutr. 2016;146(2):191–9. https://doi.org/10.3945/jn.115. 80. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, 223552. Gordon JI. An obesity-associated gut microbiome with increased 96.� Dogra S, Sakwinska O, Soh SE, Ngom-Bru C, Bruck WM, Berger capacity for energy harvest. Nature. 2006;444(7122):1027–31. B et al. Dynamics of infant gut microbiota are influenced by de- https://doi.org/10.1038/nature05414. livery mode and gestational duration and are associated with sub- 81. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced sequent adiposity. MBio. 2015;6. doi:https://doi.org/10.1128/ obesity is linked to marked but reversible alterations in the mouse mBio.02419-14. This study shows that factors such as the distal gut microbiome. Cell Host Microbe. 2008;3(4):213–23. gestational age and delivery mode strongly influence the https://doi.org/10.1016/j.chom.2008.02.015. acquisition of the early microbiota even in healthy neonates. 82. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. 97. Dogra S, Sakwinska O, Soh SE, Ngom-Bru C, Bruck WM, Berger The gut microbiota as an environmental factor that regulates fat B, et al. Rate of establishing the gut microbiota in infancy has storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–23. consequences for future health. Gut Microbes. 2015;6(5):321–5. ht tps://doi.org/10.1073/pnas.0407076101. https://doi.org/10.1080/19490976.2015.1078051. �� Curr Envir Health Rpt (2018) 5:512–521 521 98. Cong X, Judge M, Xu W, Diallo A, Janton S, Brownell EA, et al. development. Biol Psychiatry. 2018;83(2):148–59. https://doi.org/ 10.1016/j.biopsych.2017.06.021. Influence of feeding type on gut microbiome development in hos- pitalized preterm infants. Nurs Res. 2017;66(2):123–33. https:// 105. Louis P. Does the human gut microbiota contribute to the etiology doi.org/10.1097/NNR.0000000000000208. of autism spectrum disorders? Dig Dis Sci. 2012;57(8):1987–9. 99. Korpela K, Zijlmans MA, Kuitunen M, Kukkonen K, Savilahti E, https://doi.org/10.1007/s10620-012-2286-1. Salonen A, et al. Childhood BMI in relation to microbiota in 106. Ghaisas S, Maher J, Kanthasamy A. Gut microbiome in health and infancy and lifetime antibiotic use. Microbiome. 2017;5(1):26. disease: linking the microbiome-gut-brain axis and environmental https://doi.org/10.1186/s40168-017-0245-y. factors in the pathogenesis of systemic and neurodegenerative 100. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differ- diseases. Pharmacol Ther. 2016;158:52–62. https://doi.org/10. ences in fecal microbiota composition in children may predict 1016/j.pharmthera.2015.11.012. overweight. Am J Clin Nutr. 2008;87(3):534–8. 107. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, 101. Matson JL, Kozlowski AM. The increasing prevalence of autism Samuelsson A, et al. Normal gut microbiota modulates brain de- spectrum disorders. Res Autism Spect Dis. 2011;5(1):418–25. velopment and behavior. Proc Natl Acad Sci U S A. 2011;108(7): https://doi.org/10.1016/j.rasd.2010.06.004. 3047–52. https://doi.org/10.1073/pnas.1010529108. 102. Cattane N, Richetto J, Cattaneoa A. Prenatal exposure to environ- 108. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, mental insults and enhanced risk of developing schizophrenia and et al. Microbiota modulate behavioral and physiological abnor- autism Spectrum disorder: focus on biological pathways and epi- malities associated with neurodevelopmental disorders. Cell. genetic mechanisms. Neurosci Biobehav Rev. 2018. https://doi. 2013;155(7):1451–63. https://doi.org/10.1016/j.cell.2013.11.024. org/10.1016/j.neubiorev.2018.07.001. 109.�� Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano 103. Buie T, Campbell DB, Fuchs GJ, 3rd, Furuta GT, Levy J, A, et al. Microbiota transfer therapy alters gut ecosystem and Vandewater J et al. Evaluation, diagnosis, and treatment of gas- improves gastrointestinal and autism symptoms: an open-label trointestinal disorders in individuals with ASDs: a consensus re- study. Microbiome. 2017;5(1):10. https://doi.org/10.1186/ port. Pediatrics. 2010;125 Suppl 1:S1–18. doi:https://doi.org/10. s40168-016-0225-7.This study demonstrates the utility of 1542/peds.2009-1878C. microbiota transfer approaches for the treatment of a 104. Carlson AL, Xia K, Azcarate-Peril MA, Goldman BD, Ahn M, neurological disorder of high prevalence and societal cost. Styner MA, et al. Infant gut microbiome associated with cognitive
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