As human skin hosts a diverse microbiota in health and disease, there is an emerging consensus that dysregulated interactions between host and microbiome may contribute to chronic inflammatory disease of the skin. Neonatal skin is a unique habitat, structurally similar to the adult but with a different profile of metabolic substrates, environmental stressors, and immune activity. The surface is colonized within moments of birth with a bias toward maternal strains. Initial colonists are outcompeted as environmental exposures increase and host skin matures. Nonetheless, early life microbial acquisitions may have long-lasting effects on health through modulation of host immunity and competitive interactions between bacteria. Microbial ecology and its influence on health have been of interest to dermatologists for >50 years, and an explosion of recent interest in the microbiome has prompted ongoing investigations of several microbial therapeutics for dermatological disease. In this review, we consider how recent insight into the host and microbial factors driving development of the skin microbiome in early life offers new opportunities for therapeutic intervention.
Advancement in understanding molecular mechanisms of bacterial competition opens new avenues of investigation into dermatological disease.
Primary development of the skin microbiome is determined by immunological features of the cutaneous habitat.
Understanding coordinated microbial and immunological development in the pediatric patient requires a multidisciplinary synthesis of primary literature.
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Goodman, A. L. & Gordon, J. I. Our unindicted coconspirators: human metabolism from a microbial perspective. Cell Metab. 12, 111–116 (2010).
Degnan, P. H., Taga, M. E. & Goodman, A. L. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab. 20, 769–778 (2014).
Buffie, C. G. & Pamer, E. G. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13, 790–801 (2013).
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L. & Gordon, J. I. Human nutrition, the gut microbiome and the immune system. Nature 474, 327–336 (2011).
Thaiss, C. A., Zmora, N., Levy, M. & Elinav, E. The microbiome and innate immunity. Nature 535, 65–74 (2016).
Belkaid, Y. & Naik, S. Compartmentalized and systemic control of tissue immunity by commensals. Nat. Immunol. 14, 646–653 (2013).
Gordon, H. A. & Pesti, L. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol. Rev. 35, 390–429 (1971).
Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).
Gallo, R. L. Human skin is the largest epithelial surface for interaction with microbes. J. Investig. Dermatol. 137, 1213–1214 (2017).
Nakatsuji, T. et al. The microbiome extends to subepidermal compartments of normal skin. Nat. Commun. 4, 1431 (2013).
Ross, A. A., Müller, K. M., Weese, J. S. & Neufeld, J. D. Comprehensive skin microbiome analysis reveals the uniqueness of human skin and evidence for phylosymbiosis within the class Mammalia. Proc. Natl Acad. Sci. USA 115, E5786–E5795 (2018).
Grice, E. A. et al. A diversity profile of the human skin microbiota. Genome Res. 18, 1043–1050 (2008).
Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009).
Kong, H. H. & Segre, J. A. The molecular revolution in cutaneous biology: investigating the skin microbiome. J. Investig. Dermatol. 137, e119–e122 (2017).
Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).
Oh, J. et al. Biogeography and individuality shape function in the human skin metagenome. Nature 514, 59–64 (2014).
Oh, J. et al. Temporal stability of the human skin microbiome. Cell 165, 854–866 (2016).
Paller, A. S. et al. The microbiome in patients with atopic dermatitis. J. Allergy Clin. Immunol. 143, 26–35 (2019).
Fyhrquist, N. et al. Microbe-host interplay in atopic dermatitis and psoriasis. Nat. Commun. 10, 4703 (2019).
Stokholm, J. et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat. Commun. 9, 141 (2018).
Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012).
Parekh, P. J., Balart, L. A. & Johnson, D. A. The influence of the gut microbiome on obesity, metabolic syndrome and gastrointestinal disease. Clin. Transl. Gastroenterol. 6, e91 (2015).
Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2012).
Vogtmann, E. et al. Colorectal cancer and the human gut microbiome: reproducibility with whole-genome shotgun sequencing. PLoS ONE 11, e0155362 (2016).
Zeller, G. et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol. Syst. Biol. 10, 766 (2014).
Koch, R. Ueber den augenblicklichen stand der bakteriologischen choleradiagnose. Z. Hyg. Infekt. 14, 319–338 (1893).
Ogston, A. Report upon micro-organisms in surgical diseases. Br. Med. J. 1, 369.b2–369.b375 (1881).
Whitfield, A., Sabouraud, R. & MacKenna, R. W. Discussion on acne and seborrhoea, their causation and treatment. Br. Med. J. 2, 286–289 (1912).
Dr, Sabouraud et al. A discussion on the role of cocci in the pathology of the skin. Br. Med. J. 2, 794–797 (1901).
Marples, R. R., Richardson, J. F. & Newton, F. E. Staphylococci as part of the normal flora of human skin. Soc. Appl. Bacteriol. Symp. Ser. 19, 93S–99S (1990).
Schade, H. & Marchionini, A. Der säuremantel der haut (nach gaskettenmessungen). Klin. Wochenschr. 7, 12–14 (1928).
Pillsbury, D. M. & Rebell, G. The bacterial flora of the skin; factors influencing the growth of resident and transient organisms. J. Investig. Dermatol. 18, 173–186 (1952).
Marples, R. R. in Skin Bacteria and their Role in Infection (eds Maibach, H. I. & Hildick-Smith, G.) 33–41 (McGraw-Hill, New York, 1965).
Cunliffe, W. J. et al. Tetracycline and acne vulgaris: a clinical and laboratory investigation. Br. Med. J. 4, 332–335 (1973).
Holland, K. T., Cunliffe, W. J. & Roberts, C. D. Acne vulgaris: an investigation into the number of anaerobic diphtheroids and members of the Micrococcaceae in normal and acne skin. Br. J. Dermatol. 96, 623–626 (1977).
Puhvel, S. M. & Amirian, D. A. Bacterial flora of comedones. Br. J. Dermatol. 101, 543–548 (1979).
Holland, K. T., Ingham, E. & Cunliffe, W. J. A review, the microbiology of acne. J. Appl. Bacteriol. 51, 195–215 (1981).
Planet, P. J., Parker, D., Ruff, N. L. & Shinefield, H. R. Revisiting bacterial interference in the age of methicillin-resistant Staphylococcus aureus: insights into Staphylococcus aureus carriage, pathogenicity and potential control. Pediatr. Infect. Dis. J. 38, 958–966 (2019).
Gibbons, S. M. et al. Ecological succession and viability of human-associated microbiota on restroom surfaces. Appl. Environ. Microbiol. 81, 765–773 (2015).
Hogan, P. G. et al. Interplay of personal, pet, and environmental colonization in households affected by community-associated methicillin-resistant Staphylococcus aureus. J. Infect. 78, 200–207 (2019).
Lax, S. et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345, 1048–1052 (2014).
Miller, M. et al. Staphylococcus aureus in the community: colonization versus infection. PLoS ONE 4, e6708 (2009).
Mork, R. L. et al. Comprehensive modeling reveals proximity, seasonality, and hygiene practices as key determinants of MRSA colonization in exposed households. Pediatr. Res. 84, 668–676 (2018).
Mork, R. L. et al. Longitudinal, strain-specific Staphylococcus aureus introduction and transmission events in households of children with community-associated meticillin-resistant S. aureus skin and soft tissue infection: a prospective cohort study. Lancet Infect. Dis. 20, 188–198 (2019).
Fukami, T. Historical contingency in community assembly: integrating niches, species pools, and priority effects. Annu. Rev. Ecol. Evol. Syst. 46, 1–23 (2015).
Sprockett, D., Fukami, T. & Relman, D. A. Role of priority effects in the early-life assembly of the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 15, 197–205 (2018).
Hecht, A. L. et al. Strain competition restricts colonization of an enteric pathogen and prevents colitis. EMBO Rep. 17, 1281–1291 (2016).
Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237ra65 (2014).
Collado, M. C., Rautava, S., Aakko, J., Isolauri, E. & Salminen, S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci. Rep. 6, 23129 (2016).
Perez-Muñoz, M. E., Arrieta, M.-C., Ramer-Tait, A. E. & Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48 (2017).
Rodríguez, J. M. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis. 26, 26050 (2015).
Tapiainen, T. et al. Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium. Pediatr. Res. 84, 371–379 (2018).
Younge, N. et al. Fetal exposure to the maternal microbiota in humans and mice. JCI Insight 4, e127806 (2019).
de Goffau, M. C. et al. Human placenta has no microbiome but can contain potential pathogens. Nature 572, 329–334 (2019).
Theis, K. R. et al. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rRNA gene sequencing, and metagenomics. Am. J. Obstet. Gynecol. 220, 267.e1–267.e39 (2019).
Chu, D. M. et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med. 23, 314–326 (2017).
Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010).
Olm, M. R. et al. Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates. Genome Res. 27, 601–612 (2017).
Sarkany, I. & Gaylarde, C. C. Skin flora of the newborn. Lancet 1, 589–590 (1967).
Dominguez-Bello, M. G. et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat. Med. 22, 250–253 (2016).
Nishijima, K., Yoneda, M., Hirai, T., Takakuwa, K. & Enomoto, T. Biology of the vernix caseosa: a review. J. Obstet. Gynaecol. Res. 45, 2145–2149 (2019).
Bergström, A., Byaruhanga, R. & Okong, P. The impact of newborn bathing on the prevalence of neonatal hypothermia in Uganda: a randomized, controlled trial. Acta Paediatr. 94, 1462–1467 (2005).
Sarkany, I. & Gaylarde, C. C. Bacterial colonisation of the skin of the newborn. J. Pathol. Bacteriol. 95, 115–122 (1968).
Medves, J. M. & O’Brien, B. Does bathing newborns remove potentially harmful pathogens from the skin? Birth 28, 161–165 (2001).
Visscher, M. O. et al. Vernix caseosa in neonatal adaptation. J. Perinatol. 25, 440–446 (2005).
Lund, C. Bathing and beyond: current bathing controversies for newborn infants. Adv. Neonatal Care 16(Suppl 5S), S13–S20 (2016).
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).
Verster, A. J. et al. The landscape of type VI secretion across human gut microbiomes reveals its role in community composition. Cell Host Microbe 22, 411.e4–419.e4 (2017).
Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).
Capone, K. A., Dowd, S. E., Stamatas, G. N. & Nikolovski, J. Diversity of the human skin microbiome early in life. J. Investig. Dermatol. 131, 2026–2032 (2011).
Costello, E. K., Carlisle, E. M., Bik, E. M., Morowitz, M. J. & Relman, D. A. Microbiome assembly across multiple body sites in low-birthweight infants. mBio 4, e00782–00713 (2013).
Younge, N. E., Araújo-Pérez, F., Brandon, D. & Seed, P. C. Early-life skin microbiota in hospitalized preterm and full-term infants. Microbiome 6, 98 (2018).
Kennedy, E. A. et al. Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J. Allergy Clin. Immunol. 139, 166–172 (2017).
Asnicar, F. et al. Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems https://doi.org/10.1128/mSystems.00164-16 (2017).
Korpela, K. et al. Selective maternal seeding and environment shape the human gut microbiome. Genome Res. 28, 561–568 (2018).
Zhu, T. et al. Age and mothers: potent influences of children’s skin microbiota. J. Investig. Dermatol. 139, 2497.e6–2505.e6 (2019).
Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, 1237439 (2013).
Ferretti, P. et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe 24, 133.e5–145.e5 (2018).
Yassour, M. et al. Strain-level analysis of mother-to-child bacterial transmission during the first few months of life. Cell Host Microbe 24, 146.e4–154.e4 (2018).
Doege, K. et al. Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood–a meta-analysis. Br. J. Nutr. 107, 1–6 (2012).
Shin, H. et al. The first microbial environment of infants born by C-section: the operating room microbes. Microbiome 3, 59 (2015).
Lax, S. et al. Colonization and succession of hospital-associated microbiota. Sci. Transl. Med. 9, eaah6500 (2017).
Gaitanis, G. et al. Variation of cultured skin microbiota in mothers and their infants during the first year postpartum. Pediatr. Dermatol. 36, 460–465 (2019).
Evans, N. J. & Rutter, N. Development of the epidermis in the newborn. Biol. Neonate 49, 74–80 (1986).
Oranges, T., Dini, V. & Romanelli, M. Skin physiology of the neonate and infant: clinical implications. Adv. Wound Care 4, 587–595 (2015).
Hoeger, P. H. & Enzmann, C. C. Skin physiology of the neonate and young infant: a prospective study of functional skin parameters during early infancy. Pediatr. Dermatol. 19, 256–262 (2002).
Saijo, S. & Tagami, H. Dry skin of newborn infants: functional analysis of the stratum corneum. Pediatr. Dermatol. 8, 155–159 (1991).
Webster, G. F., Ruggieri, M. R. & McGinley, K. J. Correlation of Propionibacterium acnes populations with the presence of triglycerides on nonhuman skin. Appl. Environ. Microbiol. 41, 1269–1270 (1981).
Agache, P., Blanc, D., Barrand, C. & Laurent, R. Sebum levels during the first year of life. Br. J. Dermatol. 103, 643–649 (1980).
Oh, J., Conlan, S., Polley, E. C., Segre, J. A. & Kong, H. H. Shifts in human skin and nares microbiota of healthy children and adults. Genome Med. 4, 77 (2012).
Mack, M. C. et al. Development of solar UVR-related pigmentation begins as early as the first summer of life. J. Investig. Dermatol. 130, 2335–2338 (2010).
Nosanchuk, J. D. & Casadevall, A. Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob. Agents Chemother. 50, 3519–3528 (2006).
Gallo, R. L. & Nakatsuji, T. Microbial symbiosis with the innate immune defense system of the skin. J. Investig. Dermatol. 131, 1974–1980 (2011).
Lai, Y. & Gallo, R. L. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 30, 131–141 (2009).
Gläser, R. et al. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat. Immunol. 6, 57–64 (2005).
Schauber, J. et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J. Clin. Investig. 117, 803–811 (2007).
Tamoutounour, S. et al. Keratinocyte-intrinsic MHCII expression controls microbiota-induced Th1 cell responses. Proc. Natl Acad. Sci. USA 116, 23643–23652 (2019).
Thiemann, S. et al. Enhancement of IFNγ production by distinct commensals ameliorates Salmonella-induced disease. Cell Host Microbe 21, 682.e5–694.e5 (2017).
Callewaert, C. et al. IL-4Rα blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J. Investig. Dermatol. 140, 191.e7–202.e7 (2020).
Simpson, E. L. et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N. Engl. J. Med. 375, 2335–2348 (2016).
Kobayashi, T. et al. Homeostatic control of sebaceous glands by innate lymphoid cells regulates commensal bacteria equilibrium. Cell 176, 982.e16–997.e16 (2019).
Davey, M. S. et al. Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance. Nat. Commun. 8, 14760 (2017).
Kabelitz, D. Function and specificity of human gamma/delta-positive T cells. Crit. Rev. Immunol. 11, 281–303 (1992).
Sharp, L. L., Jameson, J. M., Cauvi, G. & Havran, W. L. Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1. Nat. Immunol. 6, 73–79 (2005).
Toulon, A. et al. A role for human skin-resident T cells in wound healing. J. Exp. Med. 206, 743–750 (2009).
Selvanantham, T. et al. NKT cell-deficient mice harbor an altered microbiota that fuels intestinal inflammation during chemically induced colitis. J. Immunol. 197, 4464–4472 (2016).
Doisne, J.-M. et al. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions. J. Immunol. 183, 2142–2149 (2009).
Ito, T. et al. Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J. Investig. Dermatol. 128, 1196–1206 (2008).
Gold, M. C. et al. Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress. Mucosal Immunol. 6, 35–44 (2013).
Le Bourhis, L. et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat. Immunol. 11, 701–708 (2010).
Constantinides, M. G. et al. MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science 366, eaax6624 (2019).
Hinks, T. S. C. et al. Activation and in vivo evolution of the mait cell transcriptome in mice and humans reveals tissue repair functionality. Cell Rep. 28, 3249.e5–3262.e5 (2019).
Leng, T. et al. TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions. Cell Rep. 28, 3077.e5–3091.e5 (2019).
Cordoro, K. M. et al. Skin-infiltrating, interleukin-22-producing T cells differentiate pediatric psoriasis from adult psoriasis. J. Am. Acad. Dermatol. 77, 417–424 (2017).
Scharschmidt, T. C. et al. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 43, 1011–1021 (2015).
Scharschmidt, T. C. et al. Commensal microbes and hair follicle morphogenesis coordinately drive treg migration into neonatal skin. Cell Host Microbe 21, 467.e5–477.e5 (2017).
Russler-Germain, E. V., Rengarajan, S. & Hsieh, C.-S. Antigen-specific regulatory T cell responses to intestinal microbiota. Mucosal Immunol. 10, 1375–1386 (2017).
Donaldson, G. P. et al. Gut microbiota utilize immunoglobulin A for mucosal colonization. Science 360, 795–800 (2018).
Lee, S. M. et al. Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 501, 426–429 (2013).
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).
Mehta, R. S. et al. Stability of the human faecal microbiome in a cohort of adult men. Nat. Microbiol. 3, 347–355 (2018).
Truong, D. T., Tett, A., Pasolli, E., Huttenhower, C. & Segata, N. Microbial strain-level population structure and genetic diversity from metagenomes. Genome Res. 27, 626–638 (2017).
Torow, N. & Hornef, M. W. The neonatal window of opportunity: setting the stage for life-long host-microbial interaction and immune homeostasis. J. Immunol. 198, 557–563 (2017).
Florey, H. W. The use of micro-organisms for therapeutic purposes. Yale J. Biol. Med. 19, 101–117 (1946).
Henderson, D. W. Bacterial interference. Bacteriol. Rev. 24, 167–176 (1960).
Sprunt, K. & Redman, W. Evidence suggesting importance of role of interbacterial inhibition in maintaining balance of normal flora. Ann. Intern. Med. 68, 579–590 (1968).
Schiotz, A. Uskadeliggorelse af infektionsbaerere ved difteri. Ugeskr. Læg. 71, 1382–1384 (1909).
Books received. J. Am. Med. Assoc. LIV, 422–422 (1910).
Albert, H. The treatment of diphtheria carriers. J. Am. Med. Assoc. 61, 1027–1031 (1913).
Jennings, M. A. & Sharp, A. E. Antibacterial activity of the Staphylococcus. Nature 159, 133 (1947).
Lorenz, W. F. & Ravenel, M. P. The treatment of diphtheria-carriers by overriding with Staphylococcus aureus. J. Am. Med. Assoc. LIX, 690–693 (1912).
Womer, W. A. Results of staphylococcus spray treatment in forty-two cases of diphtheria carriers. J. Am. Med. Assoc. 61, 2293–2294 (1913).
Panigrahi, P. et al. Long-term colonization of a Lactobacillus plantarum synbiotic preparation in the neonatal gut. J. Pediatr. Gastroenterol. Nutr. 47, 45–53 (2008).
Panigrahi, P. et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature 548, 407–412 (2017).
Myles, I. A. et al. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight 3, e120608 (2018).
Nakatsuji, T. et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 9, eaah4680 (2017).
Blair, J. E. & Carr, M. Staphylococci in hospital-acquired infections; types encountered in the United States. J. Am. Med. Assoc. 166, 1192–1196 (1958).
Blair, J. E. & Carr, M. Distribution of phage groups of Staphylococcus aureus in the years 1927 through 1947. Science 132, 1247–1248 (1960).
Rountree, P. M. & Freeman, B. M. Infections caused by a particular phage type of Staphylococcus aureus. Med. J. Aust. 42, 157–161 (1955).
Boris, M. et al. Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. IV. The Louisiana epidemic. Am. J. Dis. Child. 105, 674–682 (1963).
Shinefield, H. R., Ribble, J. C., Boris, M. & Eichenwald, H. F. Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. I. Preliminary observations on artificial colonzation of newborns. Am. J. Dis. Child. 105, 646–654 (1963).
Shinefield, H. R., Sutherland, J. M., Ribble, J. C. & Eichenwald, H. F. Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. II. The Ohio epidemic. Am. J. Dis. Child. 105, 655–662 (1963).
Shinefield, H. R., Boris, M., Ribble, J. C., Cale, E. F. & Eichenwald, H. F. Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. III. The Georgia epidemic. Am. J. Dis. Child. 105, 663–673 (1963).
Shinefield, H. R., Ribble, J. C., Eichenwald, H. F., Boris, M. & Sutherland, J. M. Bacterial interference: its effect on nursery-acquired infection with Staphylococcus aureus. V. An analysis and interpretation. Am. J. Dis. Child. 105, 683–688 (1963).
Light, I. J., Sutherland, J. M. & Schott, J. E. Control of a staphylococcal outbreak in a nursery: use of bacterial interference. JAMA 193, 699–704 (1965).
Russell, A. B. et al. Type VI secretion delivers bacteriolytic effectors to target cells. Nature 475, 343–347 (2011).
Russell, A. B. et al. A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host Microbe 16, 227–236 (2014).
Wexler, A. G. et al. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proc. Natl Acad. Sci. USA 113, 3639–3644 (2016).
Ross, B. D. et al. Human gut bacteria contain acquired interbacterial defence systems. Nature 575, 224–228 (2019).
Burts, M. L., DeDent, A. C. & Missiakas, D. M. EsaC substrate for the ESAT-6 secretion pathway and its role in persistent infections of Staphylococcus aureus. Mol. Microbiol. 69, 736–746 (2008).
Christensen, G. J. M. et al. Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. BMC Genomics 17, 152 (2016).
Ohr, R. J., Anderson, M., Shi, M., Schneewind, O. & Missiakas, D. EssD, a nuclease effector of the Staphylococcus aureus ESS pathway. J. Bacteriol. 199, e00528-16 (2017).
Whitney, J. C. et al. A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria. eLife 6, e26938 (2017).
Gillor, O., Etzion, A. & Riley, M. A. The dual role of bacteriocins as anti- and probiotics. Appl. Microbiol. Biotechnol. 81, 591–606 (2008).
Klaenhammer, T. R. Bacteriocins of lactic acid bacteria. Biochimie 70, 337–349 (1988).
Nes, I. F. et al. Biosynthesis of bacteriocins in lactic acid bacteria. Antonie Van Leeuwenhoek 70, 113–128 (1996).
Riley, M. A. & Wertz, J. E. Bacteriocin diversity: ecological and evolutionary perspectives. Biochimie 84, 357–364 (2002).
Mota-Meira, M., LaPointe, G., Lacroix, C. & Lavoie, M. C. MICs of mutacin B-Ny266, nisin A, vancomycin, and oxacillin against bacterial pathogens. Antimicrob. Agents Chemother. 44, 24–29 (2000).
Ikari, N. S., Kenton, D. M. & Young, V. M. Interaction in the germfree mouse intestine of colicinogenic and colicin-sensitive microorganisms. Proc. Soc. Exp. Biol. Med. 130, 1280–1284 (1969).
Riley, M. A. & Gordon, D. M. The ecological role of bacteriocins in bacterial competition. Trends Microbiol. 7, 129–133 (1999).
Sassone-Corsi, M. et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature 540, 280–283 (2016).
Chao, L. & Levin, B. R. Structured habitats and the evolution of anticompetitor toxins in bacteria. Proc. Natl Acad. Sci. USA 78, 6324–6328 (1981).
Durrett, R. & Levin, S. Allelopathy in spatially distributed populations. J. Theor. Biol. 185, 165–171 (1997).
Noble, W. C. & Willie, J. A. Interactions between antibiotic-producing and non-producing staphylococci in skin surface and sub-surface models. Br. J. Exp. Pathol. 61, 339–343 (1980).
O’Sullivan, J. N., Rea, M. C., O’Connor, P. M., Hill, C. & Ross, R. P. Human skin microbiota is a rich source of bacteriocin-producing staphylococci that kill human pathogens. FEMS Microbiol. Ecol. 95, fiy241 (2019).
O’Neill, A. M. et al. Identification of a human skin commensal bacterium that selectively kills Cutibacterium acnes. J. Investig. Dermatol. 140, 1619.e2–1628.e2 (2020).
Claesen, J. et al. Cutibacterium acnes antibiotic production shapes niche competition in the human skin microbiome. Preprint at https://doi.org/10.1101/594010 (2019).
Janek, D., Zipperer, A., Kulik, A., Krismer, B. & Peschel, A. High frequency and diversity of antimicrobial activities produced by nasal staphylococcus strains against bacterial competitors. PLoS Pathog. 12, e1005812 (2016).
DeFilipp, Z. et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381, 2043–2050 (2019).
Sorbara, M. T. & Pamer, E. G. Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them. Mucosal Immunol. 12, 1–9 (2019).
B.W.C. is supported by the National Institute of Allergy and Infectious Diseases (5 F30 AI126791).
B.W.C.: no competing interests. A.S.P.: consultant with honorarium for AbbVie, Amgen, Celgene, Dermavant, Dermira, Galderma, Eli Lilly, Forte, LEO Pharma Inc., Menlo, Novartis, Pfizer, Regeneron, and Sanofi-Genzyme.
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Casterline, B.W., Paller, A.S. Early development of the skin microbiome: therapeutic opportunities. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-01146-2