Diversity and bias in oral microbiome research: A commentary

Abstract

The oral cavity has the second largest and most diverse microbiota of the human body, harbouring over 700 microbial species [[1]Krishnan K Chen T Paster BJ. A practical guide to the oral microbiome and its relation to health and disease.Oral dis. 2017; 23: 276-286Crossref PubMed Scopus (135) Google Scholar]. Oral microbial communities are dominated by bacteria, but also contain archaea, viruses, and eukaryotes, whose roles in oral health and disease are less well understood [[2]Caselli E Fabbri C D'Accolti M et al.Defining the oral microbiome by whole-genome sequencing and resistome analysis: the complexity of the healthy picture.BMC Microbiol. 2020; 20: 120Crossref PubMed Scopus (33) Google Scholar]. Lifestyle, diet, and other host-related factors, such as ethnicity or ancestry, are associated with the composition of these microbial communities, and oral microbiome variation may affect the assessment, response, and effectiveness of disease interventions [[3]Huttenhower C Gevers D Knight R et al.Structure, function and diversity of the healthy human microbiome.Nature. 2012; 486: 207Crossref PubMed Scopus (6259) Google Scholar,[4]Fortenberry JD. The uses of race and ethnicity in human microbiome research.Trends Microbiol. 2013; 21: 165-166Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. Therefore, it is necessary to understand how oral microbiome traits are associated with oral health in diverse human populations. Currently, microbiome research is dominated by gut microbiome studies and is strongly biased towards populations of European descent [[5]Rogers GB Ward J Brown A Wesselingh SL. Inclusivity and equity in human microbiome research.Lancet. 2019; 393: 728-729Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar]. Such populations, by definition, provide a poor basis from which to understand microbiome-health relationships in under-studied populations, including groups who carry the highest burdens of disease. A similar bias is present in the oral microbiome research field. Many oral microbiome studies are conducted primarily on people living in industrialized countries, such as the United States and China. These countries maintain large funding allocations for biomedical research; for example, the United States National Institutes of Health (NIH) invested approximately USD $728 M in human microbiome research over a five-year period (2012-2016), of which $48 M was utilized for oral microbiome research [[6]Proctor L LoTempio J Marquitz A et al.A review of 10 years of human microbiome research activities at the US National Institutes of Health, fiscal years 2007-2016.Microbiome. 2019; 7: 31Crossref PubMed Scopus (22) Google Scholar]. Nevertheless, oral microbiome research within the United States has produced relatively few studies that include people from non-European backgrounds (e.g. African Americans or people of Asian or Indigenous ancestry), and even fewer of these specifically investigate non-bacterial members of the oral microbiota. The NIH Revitalization Act mandates the inclusion of racial and ethnic minorities in federally funded biomedical research, but the implementation of this mandate has been problematic [[7]Chen Jr., MS Lara PN Dang JH Paterniti DA Kelly K Twenty years post-NIH revitalization act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials.Cancer. 2014; 120 (Suppl 7): 1091-1096Crossref PubMed Scopus (205) Google Scholar]. In the global context, it is not unusual to observe oral microbiome studies using inconsistent or problematic racial and ethnic categories, or failing to mention participants’ race, ethnicity or ancestry entirely [[4]Fortenberry JD. The uses of race and ethnicity in human microbiome research.Trends Microbiol. 2013; 21: 165-166Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. Hence, studies do not reflect the diversity of ancestries even within industrialized nations that dominate the field, nor those who are most likely to benefit from improvements in oral health therapies based on microbiome research. If this pattern continues, oral microbiome research is likely to reinforce existing oral health disparities, which often fall along racial lines [[8]Jamieson LM. Racism and oral health inequities; an introduction.Community Dent Health. 2021; (Epub ahead of print. PMID: 33848410)https://doi.org/10.1922/CDH_IADRJamiesonIntro01Crossref Scopus (3) Google Scholar]. While racial categories do not represent biological reality, they intersect with factors relevant to the microbiome and oral health, such as ancestry, experience of racism, and socioeconomic status. It follows that more research should focus on underrepresented groups who experience poor oral health and could benefit most from new therapeutics. Increasing diversity in oral microbiome research could also benefit groups who are currently well-represented. For example, transitions from hunter-gatherer to agricultural or industrialized lifeways have been linked to oral health deterioration [[9]Arantes R Welch JR Tavares FG Ferreira AA Vettore MV Coimbra Jr., CEA Human ecological and social determinants of dental caries among the xavante indigenous people in central Brazil.PloS one. 2018; 13e0208312Crossref PubMed Scopus (7) Google Scholar], so understanding the mechanisms that shift oral microbiomes more broadly could provide insights that improve oral health in industrialized societies. Several barriers likely contribute to the underrepresentation of minority groups in oral microbiome research. From a research perspective, including diverse communities in the study design can pose cultural and linguistic obstacles, as researchers may be insufficiently trained to design and implement studies in these communities. Studies may also take longer to complete, and resources to recruit and retain a sufficient number of participants across different backgrounds may be limited [[7]Chen Jr., MS Lara PN Dang JH Paterniti DA Kelly K Twenty years post-NIH revitalization act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials.Cancer. 2014; 120 (Suppl 7): 1091-1096Crossref PubMed Scopus (205) Google Scholar]. From the participant perspective, participants may be justifiably reluctant to participate in biomedical research studies due to fear of exploitation, based on histories or personal experience of unethical practices, and may feel distrust toward field researchers or recruiters [[10]Wendler D Kington R Madans J et al.Are racial and ethnic minorities less willing to participate in health research?.PLoS med. 2006; 3: e19Crossref PubMed Scopus (543) Google Scholar]. Hence, the goal of increasing diversity in oral microbiome research can only be pursued with the full consent and appropriate involvement of all stakeholders and should include equal sharing of financial and non-financial benefits arising from research. There is no quick fix or single solution to these disparities. As a general principle, underrepresented communities or stakeholder groups should be involved in decision making, planning and conducting the research wherever possible, to help guard against inappropriate research practices and align research projects with community priorities. Some practical approaches to improve participation of currently underrepresented groups in oral microbiome research include positioning study sites in areas of diverse residents, employing recruitment staff with whom participants can communicate in their own language, providing travel support for participants who lack access to transportation, and creating culturally sensitive resources describing how the samples and data will be collected and stored. Researchers also need to be aware of the importance of recording race and ethnicity when planning a study [[4]Fortenberry JD. The uses of race and ethnicity in human microbiome research.Trends Microbiol. 2013; 21: 165-166Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. In the longer term, a more systematic approach to tackling this bias could be increasing the diversity in investigators/researchers, as well as grant reviewers. By drawing on these approaches, researchers and communities can find ways to redress inequalities and ensure that everyone benefits from oral microbiome research. The authors have nothing to disclose.

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