Advertisement

Development of the Human Gastrointestinal Microbiota and Insights From High-Throughput Sequencing

      Little was known about the development of the gastrointestinal (GI) tract microbiota, until recently, because of difficulties in obtaining sufficient sequence information from enough people or time points. Now, with decreased costs of DNA sequencing and improved bioinformatic tools, we can compare GI tract bacterial communities among individuals, of all ages from infancy to adulthood. Some key recent findings are that the initial bacterial community, even in the GI tract, depends strongly on delivery mode; that the process of early development of the microbiota is highly unstable and idiosyncratic; that the microbiota differs considerably among children from different countries; and that older adults have substantially different GI tract communities than younger adults, indicating that the GI tract microbiota can change throughout life. We relate these observations to different models of evolution including the evolution of senescence and suggest that probiotics be selected based on patient age. Studies of the microbiota in older people might tell us which probiotics could increase longevity. Drug metabolism varies among individuals with different microbial communities, so age- and region-specific clinical trials are required to ensure safety and efficacy.

      Keywords

      Abbreviations used in this paper:

      C-section (cesarean section), GI (gastrointestinal), rRNA (ribosomal RNA)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Metzker M.L.
        Sequencing technologies—the next generation.
        Nat Rev Genet. 2009; 11: 31-46
        • Costello E.K.
        • Lauber C.L.
        • Hamady M.
        • et al.
        Bacterial community variation in human body habitats across space and time.
        Science. 2009; 326: 1694-1697
        • Eckburg P.B.
        • Bik E.M.
        • Bernstein C.N.
        • et al.
        Diversity of the human intestinal microbial flora.
        Science. 2005; 308: 1635-1638
        • Qin J.
        • Li R.
        • Raes J.
        • et al.
        A human gut microbial gene catalogue established by metagenomic sequencing.
        Nature. 2010; 464: 59-65
        • Turnbaugh P.J.
        • Hamady M.
        • Yatsunenko T.
        • et al.
        A core gut microbiome in obese and lean twins.
        Nature. 2009; 457: 480-484
        • Dethlefsen L.
        • Relman D.A.
        Microbes and health sackler colloquium: incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation.
        Proc Natl Acad Sci U S A. 2011; 108: 4554-4561
        • Domínguez-Bello M.G.
        • Costtello E.K.
        • Contreras M.
        • et al.
        Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.
        Proc Natl Acad Sci U S A. 2010; 107: 11971-11975
        • Palmer C.
        • Bik E.M.
        • DiGiulio D.B.
        • et al.
        Development of the human infant intestinal microbiota.
        PLoS Biol. 2007; 5: e177
        • Ravel J.
        • Gajer P.
        • Abdo Z.
        • et al.
        Microbes and health sackler colloquium: vaginal microbiome of reproductive-age women.
        Proc Natl Acad Sci U S A. 2011; 108: 4680-4687
        • Claesson M.J.
        • Cusack S.
        • O'Sullivan O.
        • et al.
        Microbes and health sackler colloquium: composition, variability, and temporal stability of the intestinal microbiota of the elderly.
        Proc Natl Acad Sci U S A. 2011; 108: 4680-4687
        • Biagi E.
        • Nylund L.
        • Candela M.
        • et al.
        Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians.
        PLoS One. 2010; 5: e10667
        • DiGiulio D.B.
        • Romero R.
        • Amogan H.P.
        • et al.
        Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation.
        PLoS One. 2008; 3: e3056
        • Ley R.E.
        • Lozupone C.A.
        • Hamady M.
        • et al.
        Worlds within worlds: evolution of the vertebrate gut microbiota.
        Nat Rev Microbiol. 2008; 6: 776-788
        • Wilson M.
        Bacteriology of humans: an ecological perspective.
        Blackwell Publishing, Oxford, UK2008
        • Costello E.K.
        • Lauber C.L.
        • Hamady M.
        • et al.
        Bacterial community variation in human body habitats across space and time.
        Science. 2009; 326: 1694-1697
        • Biasucci G.
        • Benenati B.
        • Morelli L.
        • et al.
        Cesarean delivery may affect the early biodiversity of intestinal bacteria.
        J Nutr. 2008; 138: S1796-S1800
        • Connell J.H.
        • Slatyer R.O.
        Mechanisms of succession in natural communities and their role in community stability and organization.
        Am Naturalist. 1977; 111: 1119-1144
        • Hyman R.W.
        • Fukushima M.
        • Diamond L.
        • et al.
        Microbes on the human vaginal epithelium.
        Proc Natl Acad Sci U S A. 2005; 102: 7952-7957
        • Zhou X.
        • Brown C.J.
        • Abdo Z.
        • et al.
        Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women.
        Isme J. 2007; 1: 121-133
        • Fanaro S.
        • Chierici R.
        • Guerrini P.
        • et al.
        Intestinal microflora in early infancy: composition and development.
        Acta Paediatr Suppl. 2003; 91: 48-55
        • Favier C.F.
        • Vaughan E.E.
        • De Vos W.M.
        • et al.
        Molecular monitoring of succession of bacterial communities in human neonates.
        Appl Environ Microbiol. 2002; 68: 219-226
        • Ley R.E.
        • Hamady M.
        • Lozupone C.
        • et al.
        Evolution of mammals and their gut microbes.
        Science. 2008; 320: 1647-1651
        • Benson A.K.
        • Kelly S.A.
        • Legge R.
        • et al.
        Individuality in gut microbiota composition is a complex, polygenic trait shaped by multiple environmental and host genetic factors.
        Proc Natl Acad Sci U S A. 2010; 107: 18933-18938
        • Zoetendal E.G.
        • Akkermans A.D.L.
        • Akkermans-van Vliet W.M.
        • et al.
        The host genotype affects the bacterial community in the human gastronintestinal tract.
        Microb Ecol Health Dis. 2001; 13: 129-134
        • Turnbaugh P.J.
        • Hamady M.
        • Yatsunenko T.
        • et al.
        A core gut microbiome in obese and lean twins.
        Nature. 2009; 457: 480-484
        • Mackie R.I.
        • Sghir A.
        • Gaskins H.R.
        Developmental microbial ecology of the neonatal gastrointestinal tract.
        Am J Clin Nutr. 1999; 69: S1035-S1045
        • Kim K.Y.
        • Kim Y.S.
        • Kim D.
        Distribution characteristics of airborne bacteria and fungi in the general hospitals of Korea.
        Ind Health. 2010; 48: 236-243
        • Grönlund M.M.
        • Lehtonen O.P.
        • Eerola E.
        Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after Cesarean delivery.
        J Pediatr Gastroenterol Nutr. 1999; 28: 19-25
        • Penders J.
        • Thijs C.
        • Vink C.
        • et al.
        Factors influencing the composition of the intestinal microbiota in early infancy.
        Pediatrics. 2006; 118: 511-521
        • Biasucci G.
        • Rubini M.
        • Riboni S.
        • et al.
        Mode of delivery affects the bacterial community in the newborn gut.
        Early Hum Dev. 2010; 86: 13-15
        • Watson J.
        • Jones R.C.
        • Cortes C.
        • et al.
        Community-associated methicillin-resistant Staphylococcus aureus infection among healthy newborns—Chicago and Los Angeles County, 2004. (reprinted from MMWR 2006;55:329–332).
        JAMA. 2006; 296: 36-38
        • Penders J.
        • Thijs C.
        • van den Brandt P.A.
        • et al.
        Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study.
        Gut. 2007; 56: 661-667
        • Bager P.
        • Wohlfahrt J.
        • Westergaard T.
        Caesarean delivery and risk of atopy and allergic disease: meta-analyses.
        Clin Exp Allergy. 2008; 38: 634-642
        • Negele K.
        • Heinrich J.
        • Borte M.
        • et al.
        Mode of delivery and development of atopic disease during the first 2 years of life.
        Pediatr Allergy Immunol. 2004; 15: 48-54
        • Kuitunen M.
        • Kukkonen K.
        • Juntunen-Backman K.
        • et al.
        Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort.
        J Allergy Clin Immunol. 2009; 123: 335-341
        • Backhed F.
        • Ding H.
        • Wang T.
        • et al.
        The gut microbiota as an environmental factor that regulates fat storage.
        Proc Natl Acad Sci U S A. 2004; 101 (15718–1523)
        • Samuel B.S.
        • Shaito A.
        • Motoike T.
        • et al.
        Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.
        Proc Natl Acad Sci U S A. 2008; 105: 16767-16772
        • Martens E.C.
        • Chiang H.C.
        • Gordon J.I.
        Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.
        Cell Host Microbe. 2008; 4: 447-457
        • Backhed F.
        • Manchester J.K.
        • Semenkovich C.F.
        • et al.
        Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
        Proc Natl Acad Sci U S A. 2007; 104: 979-984
        • Nicholson J.K.
        • Holmes E.
        • Wilson I.D.
        Gut microorganisms, mammalian metabolism and personalized health care.
        Nat Rev Microbiol. 2005; 3: 431-438
        • Swann J.
        • Wang Y.
        • Abecia L.
        • et al.
        Gut microbiome modulates the toxicity of hydrazine: a metabonomic study.
        Mol Biosyst. 2009; 5: 351-355
        • Boullier S.
        • Nougayrede J.P.
        • Marches O.
        • et al.
        Genetically engineered enteropathogenic Escherichia coli strain elicits a specific immune response and protects against a virulent challenge.
        Microbes Infect. 2003; 5: 857-867
        • Wells C.L.
        Relationship between intestinal microecology and the translocation of intestinal bacteria.
        Antonie Van Leeuwenhoek. 1990; 58: 87-93
        • Mazmanian S.K.
        • Liu C.H.
        • Tzianabos A.O.
        • et al.
        An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.
        Cell. 2005; 122: 107-118
        • Are A.
        • Aronsson L.
        • Wang S.
        • et al.
        Enterococcus faecalis from newborn babies regulate endogenous PPARγ activity and IL-10 levels in colonic epithelial cells.
        Proc Natl Acad Sci U S A. 2008; 105: 1943-1948
        • Matsumiya Y.
        • Kato N.
        • Watanabe K.
        • et al.
        Molecular epidemiological study of vertical transmission of vaginal Lactobacillus species from mothers to newborn infants in Japanese, by arbitrarily primed polymerase chain reaction.
        J Infect Chemother. 2002; 8: 43-49
        • Tannock G.
        • Fuller R.
        • Smith S.
        • et al.
        Plasmid profiling of members of the family Enterobacteriaceae, lactobacilli, and bifidobacteria to study the transmission of bacteria from mother to infant.
        J Clin Microbiol. 1990; 28: 1225-1228
        • Vaishampayan P.A.
        • Kuehl J.V.
        • Froula J.L.
        • et al.
        Comparative metagenomics and population dynamics of the gut microbiota in mother and infant.
        Genome Biol Evol. 2010; 6: 53-66
        • Koenig J.E.
        • Spor A.
        • Scalfone N.
        • et al.
        Microbes and health sackler colloquium: succession of microbial consortia in the developing infant gut microbiome.
        Proc Natl Acad Sci U S A. 2011; 108: 4578-4585
        • Macarthur R.H.
        • Wison E.O.
        The theory of island biogeography.
        Princeton University Press, Princeton, NJ1967
        • Falush D.
        • Wirth T.
        • Linz B.
        • et al.
        Traces of human migrations in Helicobacter pylori populations.
        Science. 2003; 299: 1582-1585
        • Moodley Y.
        • Linz B.
        • Yamaoka Y.
        • et al.
        The peopling of the Pacific from a bacterial perspective.
        Science. 2009; 323: 527-530
        • Dethlefsen L.
        • Huse S.
        • Sogin M.L.
        • et al.
        The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
        PLoS Biol. 2008; 6: e280
        • De Filippo C.
        • Cavalieri D.
        • Di Paola M.
        • et al.
        Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.
        Proc Natl Acad Sci U S A. 2010; 107: 14691-14696
        • Rajilic-Stojanovic M.
        • Heilig H.G.
        • Molenaar D.
        • et al.
        Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults.
        Environ Microbiol. 2009; 11: 1736-1751
        • Clayton T.A.
        • Baker D.
        • Lindon J.C.
        • et al.
        Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.
        Proc Natl Acad Sci U S A. 2009; 106: 14728-14733
        • Coppa G.V.
        • Zampini L.
        • Galeazzi T.
        • et al.
        Prebiotics in human milk: a review.
        Dig Liver Dis. 2006; 38: S291-S294
        • Zivkovic A.M.
        • German J.B.
        • Lebrilla C.B.
        • et al.
        Microbes and health sackler colloquium: human milk glycobiome and its impact on the infant gastrointestinal microbiota.
        Proc Natl Acad Sci U S A. 2011; 108: 4653-4658
        • Hehemann J.
        • Correc G.
        • Barbeyron T.
        • et al.
        Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota.
        Nature. 2010; 464: 908-912
        • Stearns S.C.
        Trade-offs in life-history evolution.
        Funct Ecol. 1989; 3: 259-268
        • Koons D.N.
        • Grand J.B.
        • Zinner B.
        • et al.
        Transient population dynamics: relation to life history and initial population state.
        Ecol Model. 2005; 185: 283-297
        • Hayflick L.
        The cell biology of human aging.
        Sci Am. 1980; 242: 58-65
        • Prinzinger R.
        Programmed ageing: the theory of maximal metabolic scope.
        EMBO Rep. 2005; 6 (S14–S9)
        • Harley C.B.
        Telomere loss: mitotic clock or genetic time bomb?.
        Mutat Res. 1991; 256: 271-282
        • Williams G.C.
        Pleiotropy, natural selection and the evolution of senescence.
        Evolution. 1957; 11: 398-411
        • Hamilton W.D.
        The moulding of senescence by natural selection.
        J Theor Biol. 1966; 12: 12-45
        • Lee R.
        Sociality, selection, and survival: simulated evolution of mortality with intergenerational transfers and food sharing.
        Proc Natl Acad Sci U S A. 2008; 105: 7124-7128
        • Baumann P.
        • Baumann L.
        • Lai C.Y.
        • et al.
        Genetics, physiology, and evolutionary relationships of the genus Buchnera: intracellular symbionts of aphids.
        Annu Rev Microbiol. 1995; 49: 55-94
        • Blaser M.J.
        • Webb G.
        Host demise as a beneficial function of indigenous microbiota in multicellular hosts.
        (Lake Tahoe, NV)2005
        • Blaser M.J.
        • Kirschner D.
        The equilibria that allow bacterial persistence in human hosts.
        Nature. 2007; 449: 843-849
        • Atherton J.C.
        • Blaser M.J.
        Coadaptation of Helicobacter pylori and humans: ancient history, modern implications.
        J Clin Invest. 2009; 119: 2475-2487
        • Perry S.
        • de Jong B.C.
        • Solnick J.V.
        • et al.
        Infection with Helicobacter pylori is associated with protection against tuberculosis.
        PLoS One. 2010; 5: e8804
        • Blaser M.J.
        Who are we?.
        EMBO Rep. 2006; 7: 956-960
        • Schiffrin E.J.
        • Parlesak A.
        • Bode C.
        • et al.
        Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions.
        Br J Nutr. 2009; 101: 961-966
        • Guillemard E.
        • Tondu F.
        • Lacoin F.
        • et al.
        Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial.
        Br J Nutr. 2010; 103: 58-68
        • Tiihonen K.
        • Ouwehand A.C.
        • Rautonen N.
        Human intestinal microbiota and healthy ageing.
        Ageing Res Rev. 2010; 9: 107-116
        • Makino S.
        • Ikegami S.
        • Kume A.
        • et al.
        Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp.
        Br J Nutr. 2010; 104: 998-1006
        • Boge T.
        • Remigy M.
        • Vaudaine S.
        • et al.
        A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials.
        Vaccine. 2009; 27: 5677-5684
        • Vidal K.
        • Benyacoub J.
        • Moser M.
        • et al.
        Effect of Lactobacillus paracasei NCC2461 on antigen-specific T-cell mediated immune responses in aged mice.
        Rejuvenation Res. 2008; 11: 957-964
        • An H.M.
        • Baek E.H.
        • Jang S.
        • et al.
        Efficacy of lactic acid bacteria (LAB) supplement in management of constipation among nursing home residents.
        Nutr J. 2010; 9: 5
        • Mikelsaar M.
        • Stsepetova J.
        • Hutt P.
        • et al.
        Intestinal Lactobacillus sp. is associated with some cellular and metabolic characteristics of blood in elderly people.
        Anaerobe. 2010; 16: 240-246
        • Martin C.R.
        • Walker W.A.
        Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis.
        Semin Perinatol. 2008; 32: 127-137
        • Tatum Jr, P.M.
        • Harmon C.M.
        • Lorenz R.G.
        • et al.
        Toll-like receptor 4 is protective against neonatal murine ischemia-reperfusion intestinal injury.
        J Pediatr Surg. 2010; 45: 1246-1255