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Tooth Be Told, Genetics Influences Oral Microbiome

2017; Cell Press; Volume: 22; Issue: 3 Linguagem: Inglês

10.1016/j.chom.2017.08.018

1934-6069

Emily Davenport,

Digestive system and related health

The mix of bacteria that coat our teeth impact oral health, but it remains unclear what factors govern their composition. In this issue of Cell Host & Microbe, Gomez et al., 2017Gomez A. Espinoza J.L. Harkins D.M. Leong P. Saffery R. Bockmann M. Tarralba M. Kuelbs C. Kodukula R. Inman J. et al.Cell Host Microbe. 2017; 22 (this issue): 269-278Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar examine the relationship between host genetics and the oral microbiome in the context of health and disease. The mix of bacteria that coat our teeth impact oral health, but it remains unclear what factors govern their composition. In this issue of Cell Host & Microbe, Gomez et al., 2017Gomez A. Espinoza J.L. Harkins D.M. Leong P. Saffery R. Bockmann M. Tarralba M. Kuelbs C. Kodukula R. Inman J. et al.Cell Host Microbe. 2017; 22 (this issue): 269-278Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar examine the relationship between host genetics and the oral microbiome in the context of health and disease. The oral cavity houses many environments for microbes to colonize. The tooth surface in particular serves as a tethering point, allowing bacterial biofilms to develop. When not kept in check, these communities contribute to poor oral health. For instance, several bacterial taxa tend to associate with dental caries, including Streptococcus mutans and Lactobacillus species. Your dentist tells you to brush, floss, and avoid sugar, but are there other factors that determine which bacteria live in your mouth? In a study published in this issue of Cell Host & Microbe, Gomez et al. demonstrate the role of host genetics in determining composition of the bacteria that live on tooth surfaces right next to the gums (supragingival plaque) and further from the gum line. They collected microbiome, dental caries, and sugar consumption data for 485 twins aged 5–11. By comparing the microbiomes of monozygotic (identical; MZ) and dizygotic (fraternal; DZ) twin pairs, they estimate heritability (h2), which is the difference in the correlation of MZ and DZ twin pairs, for the relative abundances of microbial taxa present in at least half of their samples. Of the 91 common bacteria examined, almost half show heritability of at least 0.2. Of these, the heritability estimates of many taxa are fairly high, including Prevotella pallens (h2 = 0.65), a Veillonella species (h2 = 0.60), and Corynebacterium durum (h2 = 0.54), clearly demonstrating the contribution of the host genome to oral colonization by these bacteria. These results mesh well with the first genome-wide association study of microbiomes, which examined multiple body sites profiled by the Human Microbiome Project (HMP) (Blekhman et al., 2015Blekhman R. Goodrich J.K. Huang K. Sun Q. Bukowski R. Bell J.T. Spector T.D. Keinan A. Ley R.E. Gevers D. Clark A.G. Genome Biol. 2015; 16: 191Crossref PubMed Scopus (429) Google Scholar). For both saliva and supragingival plaque microbiomes from the HMP, the more similar a pair of individuals' genomes, the more similar their microbiome composition—pointing to a role of host genetics. However, given that the HMP samples consist of unrelated individuals, heritability could not be directly measured. The results of Gomez et al. fill in this gap. Moreover, specific results from the two studies support each other. Several taxa that Blekhman et al. observed to be associated with host genetic variation are now reported as heritable by Gomez et al. In supragingival plaque from the HMP study, genus Aggregatibacter was associated with genetic variants on chromosomes 3 and 11, while in the twin study an Aggregatibacter OTU is heritable (h2 = 0.35). Additionally, in saliva from the HMP study, genus Leptotrichia was associated with genetic variants on chromosome 15, while in the twin study a Leptotrichia OTU is highly heritable (h2 = 0.54). The role of the host genetics in determining oral microbiomes seems to differ from its role in the gut, the most well-studied body site to date. Typically, a much smaller percentage of bacteria in the gut have heritable abundances, somewhere between 10% and 20%. Those also tend to have lower heritability estimates, usually no more than 0.4 (Goodrich et al., 2016Goodrich J.K. Davenport E.R. Waters J.L. Clark A.G. Ley R.E. Science. 2016; 352: 532-535Crossref PubMed Scopus (175) Google Scholar). However, one caveat worth pointing out is the difference in the ages of participants between the gut and oral studies. Gut studies typically include adults, many of whom are older. Not only does the new oral microbiome study from Gomez et al. focus on younger participants than the gut studies, but heritability estimates decrease with age for the most heritable taxon, Prevotella pallens. Would the heritability of gut microbe abundances be higher in children than in the current estimates from adults? Another difference between gut and oral sites is the relationship of heritable taxa to the rest of the microbial community. Heritable oral taxa tend to lie on the periphery of microbiome networks and do not co-occur with each other (Gomez et al., 2017Gomez A. Espinoza J.L. Harkins D.M. Leong P. Saffery R. Bockmann M. Tarralba M. Kuelbs C. Kodukula R. Inman J. et al.Cell Host Microbe. 2017; 22 (this issue): 269-278Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar). In contrast, in the gut most heritable taxa co-occur with each other, forming a clique (Goodrich et al., 2016Goodrich J.K. Davenport E.R. Waters J.L. Clark A.G. Ley R.E. Science. 2016; 352: 532-535Crossref PubMed Scopus (175) Google Scholar). The genetic and environmental factors that contribute to these differences remain unknown. Those discrepancies aside, one similarity between the two body sites is that the most heritable bacteria tend to be more highly abundant in states of health rather than disease. For instance, in the gut, increased abundance of the most heritable taxa, Christensenellaceae, is associated with leanness (Goodrich et al., 2016Goodrich J.K. Davenport E.R. Waters J.L. Clark A.G. Ley R.E. Science. 2016; 352: 532-535Crossref PubMed Scopus (175) Google Scholar). In the oral cavity, higher abundances of Prevotella pallens and other heritable taxa occur in individuals lacking dental caries. Whether increased abundances of the heritable taxa at other body sites associate with health rather than disease is another open question. Given that a sizeable proportion of common oral microbe abundances are heritable, the next question is which host genes, genetic variants, and physiological processes potentially underlie this heritability? Human saliva and mucosal surfaces contain a number of molecules encoded by the host genomes that likely play a role in the process, including mucins, immune compounds, enzymes, and taste receptors (Figure 1). Top candidates include proline-rich proteins, or PRPs. These proteins make up the largest component of human saliva and contain putatively functional polymorphisms (Azen, 1993Azen E.A. Crit. Rev. Oral Biol. Med. 1993; 4: 479-485Crossref PubMed Scopus (48) Google Scholar). Another candidate is salivary amylase, an enzyme responsible for breaking down starches. This enzyme exists in variable copy number across human populations and is capable of binding several bacterial species common in oral microbiomes (Oppenheim et al., 2007Oppenheim F.G. Salih E. Siqueira W.L. Zhang W. Helmerhorst E.J. Ann. N Y Acad. Sci. 2007; 1098: 22-50Crossref PubMed Scopus (162) Google Scholar, Perry et al., 2007Perry G.H. Dominy N.J. Claw K.G. Lee A.S. Fiegler H. Redon R. Werner J. Villanea F.A. Mountain J.L. Misra R. et al.Nat. Genet. 2007; 39: 1256-1260Crossref PubMed Scopus (984) Google Scholar). Other candidates include histatins, which are unique to saliva and have antimicrobial properties in vitro (Kavanagh and Dowd, 2004Kavanagh K. Dowd S. J. Pharm. Pharmacol. 2004; 56: 285-289Crossref PubMed Scopus (142) Google Scholar); immune molecules, such as IgA or defensins; and taste receptor genes, such as TS2R38, TAS1R2, and GNAT3. Recently, genetic variation near a mucin gene, MUC7, was found to be significantly associated with oral microbiome composition. MUC7 encodes one of the most abundant proteins in saliva, MUCIN-7. It contains variable numbers of proline, threonine, and serine (PTS) repeats that act as the primary sites for O-glycosylation, which is a target for microbes in saliva. Variants near MUC7 are associated with Neisseria abundance in supragingival plaque (Xu et al., 2017Xu D. Pavlidis P. Taskent R.O. Alachiotis N. Flanagan C. DeGiorgio M. Blekhman R. Ruhl S. Gokcumen O. Mol. Biol. Evol. 2017; (Published online July 21, 2017)https://doi.org/10.1093/molbev/msx206Crossref Scopus (37) Google Scholar). Meanwhile, in Gomez et al., a Neisseria OTU is also heritable (h2 = 0.38) (Gomez et al., 2017Gomez A. Espinoza J.L. Harkins D.M. Leong P. Saffery R. Bockmann M. Tarralba M. Kuelbs C. Kodukula R. Inman J. et al.Cell Host Microbe. 2017; 22 (this issue): 269-278Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar). Copy-number variation (CNV) of PTS repeats in MUC7 potentially explains a portion of this heritability, highlighting the understudied role that CNVs might play underlying heritability of microbial abundance. In addition to what host genetic variants and physiological processes underlie oral microbiome heritability, the results of this study open up a floodgate of other questions to be addressed. For example, are the non-bacterial members of the oral microbiome, such as Candida albicans, which is an indicator of oral health, also heritable? Do the heritable oral bacteria identified in children remain heritable in adults? How do modern oral hygiene practices affect estimates of heritability? Would oral microbiomes collected from populations that do not regularly visit dentists or use toothpastes with antimicrobial compounds show different estimates of heritability? Finally, how does heritability relate to the placement of microbes in 3D space in the oral cavity? A recent study identified hedgehog structures in oral microbiomes using imaging techniques. Stalks made of Corynebacterium connected the structure to the tooth, while the periphery consisted of Streptococcus and other species (Mark Welch et al., 2016Mark Welch J.L. Rossetti B.J. Rieken C.W. Dewhirst F.E. Borisy G.G. Proc. Natl. Acad. Sci. USA. 2016; 113: E791-E800Crossref PubMed Scopus (440) Google Scholar). Given that Corynebacterium species are heritable while Streptococcus species are not, is it more than coincidence that the heritable species lie close to the human structures to which they attach? This research clearly opens up many doors for future study. In the meantime, I'll be taking the advice of the inspirational poster hanging in my dentist's office: Keep calm and floss on. Host Genetic Control of the Oral Microbiome in Health and DiseaseGomez et al.Cell Host & MicrobeSeptember 13, 2017In BriefGomez et al. examine the supragingival plaque microbiome of 5- to 11-year-old twins and find that the early oral microbiome is shaped by both heritable and environmental factors. However, the most heritable bacteria diminish in abundance with age, and potentially cariogenic taxa are not controlled by host genetics. Full-Text PDF Open Archive