Role of the Microbiome in Human Development Gut: First Published As 10.1136/Gutjnl-2018-317503 on 22 January 2019
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Recent advances in basic science Role of the microbiome in human development Gut: first published as 10.1136/gutjnl-2018-317503 on 22 January 2019. Downloaded from Maria Gloria Dominguez-Bello,1 Filipa Godoy-Vitorino,2 Rob Knight,3 Martin J Blaser4 1Department of Biochemistry ABStract remain unknown. Abrupt changes in environmental and Microbiology, Rutgers, the The host-microbiome supraorganism appears to have conditions can lead to mal-adaptations (adaptations State University of New Jersey, that were beneficial when first took place, but not New Brunswick, New Jersey, coevolved and the unperturbed microbial component USA of the dyad renders host health sustainable. This anymore under new environmental conditions). 2Department of Microbiology coevolution has likely shaped evolving phenotypes in Today, modernisation and urbanisation pose exactly and Medical Zoology, University all life forms on this predominantly microbial planet. this challenge to human health. of Puerto Rico, School of The microbiota seems to exert effects on the next Together with their microbionts (microbiota Medicine, San Juan, Puerto Rico, USA generation from gestation, via maternal microbiota and members), hosts evolved an immune system, which 3Department of Computer immune responses. The microbiota ecosystems develop, prevents microbial colonisation in the topological Science and Engineering, restricted to their epithelial niches by the host immune interior of the body. Host immune systems evolved University of California, San system, concomitantly with the host chronological complex mechanisms to identify and destroy Diego, California, USA 4 invading microbes, whether they are microbionts Department of Medicine, New development, providing early modulation of physiological York University Langone Medical host development and functions for nutrition, immunity or primary pathogens that cross into forbidden Center, New York City, New and resistance to pathogens at all ages. Here, we review territories. Immune molecules evolved more than York, USA the role of the microbiome in human development, 500 million years ago, in choanoflagellates, unicel- including evolutionary considerations, and the maternal/ lular progenitors of metazoans,7 and there is Correspondence to fetal relationships, contributions to nutrition and growth. growing evidence that the innate immune system— Professor Maria antimicrobial peptides and repertoire of pattern Gloria Dominguez-Bello, We also discuss what constitutes a healthy microbiota, Department of Biochemistry and how antimicrobial modern practices are impacting the recognition receptors—evolved in response to the Microbiology, Rutgers, the State human microbiota, the associations between microbiota need for controlling the epithelium-colonising University of New Jersey, New perturbations, host responses and diseases rocketing in microbiota.8 Brunswick, NJ 08901, USA; urban societies and potential for future restoration. The human immune system restricts microbiota mg. dominguez- bello@ rutgers. edu to their natural niches in the body ‘exterior’ and invaginations: epithelia that cover the body (such Received 3 September 2018 as skin and mucosa) and the gut, which, strictly Revised 15 December 2018 speaking, is a hollow tube that traverses the body Accepted 31 December 2018 EVOLUTION OF THE MICROBIOTA 1 with the influx of external materials (diet). Thus, Published Online First Bacteria arose about 3.8 billion years ago, and 22 January 2019 the eukaryotic lineage, which includes humans, the microbiota occupies the interface between our http://gut.bmj.com/ arose after the oxygenation of earth’s atmosphere bodies and the exterior, and interactions with the 2.2–2.4 billion years ago.2 Together with archaea, environment (including diet, sun-light, bathing, protists and fungi, bacteria remained free-living cosmetics) cross this interface. The microbiota is at single cells although some became host-associated. the same time self and non-self: it is part of our Thus, an animal holobiont (the animal host and its biology, but consists of fast-evolving entities that evolved microbial communities)3 spans the phylo- respond rapidly on physiological, ecological and genetic tree: the animal host, plus its associated evolutionary timescales to external perturbations on September 27, 2021 by guest. Protected copyright. microbiota such as bacteria, archaea, fungi, protists, in ways that affect our phenotypes (figure 1). The helminths and viruses (figure 1). The collective gut microbiota have been shown to impact diverse genome content of microbiota or the microbial physiological processes ranging from adiposity/ metagenome was coined the microbiome,4 although obesity, to energy metabolism, blood pressure microbiome and microbiota are currently used control, glucose homeostasis, clotting risks or even interchangeably. behaviour. In each case, there are mechanistic ties By coevolving with the host, the microbiome has between gut microbes, metabolites they generate shaped phenotypes in our ancestral lineages. The and host receptors and phenotypic responses. congruence of the phylogenetic trees of intestinal Evolutionary considerations are crucial to under- bacterial microbiota and primates5 demonstrates standing the nature of microbial-host interactions, host-microbiota coevolution and implies with- perturbations and health consequences and will in-species transmission of microbes across gener- ultimately need to be understood and exploited in ations. Through the process of natural selection, order to prevent and treat ‘modern’ diseases. © Author(s) (or their mutations lead to evolutionary adaptations to employer(s)) 2019. Re-use permitted under CC BY-NC. No environmental conditions and increased fitness in DEVELOPMENT AND THE MICROBIOTA: FROM commercial re-use. See rights these environments. Human environments have FertILISatION TO BIrtH and permissions. Published changed dramatically during human evolution, and In some insects, bacteria colonise egg capsules by BMJ. dietary changes and exposures to famine have been during mating, and the individual is colonised 9 To cite: Dominguez- major selective pressures. While there is evidence before hatching. In mammals, fertilisation Bello MG, Godoy-Vitorino F, of adaptive survival traits to starvation on the occurs in an immune-protected organ, the uterus. Knight R, et al. Gut human genome,6 human microbiome adaptations However, immune protection means lack of colo- 2019;68:1108–1114. that offer energy-sparing traits for the human host nisation, but not necessarily sterility at all times. 1108 Dominguez-Bello MG, et al. Gut 2019;68:1108–1114. doi:10.1136/gutjnl-2018-317503 Recent advances in basic science Box 1 Highlights of the holobiont evolution Gut: first published as 10.1136/gutjnl-2018-317503 on 22 January 2019. Downloaded from ► Evolution of all complex life forms has occurred in associations with bacteria, the first forms of life on earth. ► The human body carries representatives of all branches of the tree of life (Animalia-Homo sapiens, and protozoa, fungi, archaea, bacteria conforming the microbiota). ► The microbiota has been transferred throughout generations of humans, with the matrilineal line transferring the primordial birth microbiota. ► The vertical human transmission has led to conservation of a phylogenetic signal in human microbiota communities. mammals, the Monotremes, lay eggs through a single canal— the cloaca—shared for excretion and reproduction. Placental mammals evolved separate canals for reproduction (vagina), excretion of faeces (anus) and urine (urethra), and the birth canal Figure 1 Evolution of the holobiont and vertical transmission through is always adjacent to the rectum (but not the urethra), providing human generations. an efficient mechanism for intergenerational transmission of both vaginal and gut microbes. Rupture of the chorioamniotic Indeed, it seems possible that some bacterial cells of the uterine membrane allows exposure of the baby to the maternal vaginal cervix10 may enter with the sperm during fertilisation and reach and perineal faecal microbes. Indeed, prolonged labour poses 28 the egg at the time of fertilisation, implantation or early embry- a risk of infection by opportunistic microbionts. Infants are onic development. Regardless, immunity appears to preclude the naturally born with their skin and mouth covered by maternal 29 30 establishment of a microbial community in immune-protected inocula and have swallowed these microbes, supported by 31 31 organs. Uterus, placenta, fetus as well as blood appear void of the observation of both DNA and live bacteria in the meco- a microbiota, although they may contain bacterial DNA or even nium. Thus, we inherit the primordial microbiota from our some isolated live bacteria. There is a current controversy about mothers, grandmothers and further on the matrilineal line, with whether the presence of bacterial DNA contradicts the notion of microbial vertical transmission extending back to earlier ances- 32 sterility, but the presence of circulating bacterial DNA, such in tors (box 1). Whether the primordial inoculum contains most the blood11 or placenta,12 or even sporadic presence of an alive microbes that will be nurtured by the child, and which maternal intruder bacteria does not demonstrate a living blood micro- strains colonise which parts of the baby’s body and their func- biota and does not challenge the current paradigm of sterility tions, the paternal and sibling contribution along with the infant’s