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Host-associated microbiota form complex microbial communities that are increasingly associated with host behavior and disease. While these microbes include bacterial, archaeal, viral, and eukaryotic constituents, most studies have focused on bacteria due to their dominance in the human host and available tools for investigation. Accumulating evidence suggests microbial eukaryotes in the microbiome play pivotal roles in host health, but our understandings of these interactions are limited to a few readily identifiable taxa because of technical limitations in unbiased eukaryote exploration. Here, we combined cell sorting, optimized eukaryotic cell lysis, and shotgun sequencing to accelerate metagenomic discovery and analysis of host-associated microbial eukaryotes. Using synthetic communities with a 1% microbial eukaryote representation, the eukaryote-optimized cell lysis and DNA recovery method alone yielded a 38-fold increase in eukaryotic DNA. Automated sorting of eukaryotic cells from stool samples of healthy adults increased the number of microbial eukaryote reads in metagenomic pools by up to 28-fold compared to commercial kits. Read frequencies for identified fungi increased by 10,000× on average compared to the Human Microbiome Project and allowed for the identification of novel taxa, de novo assembly of contigs from previously unknown microbial eukaryotes, and gene prediction from recovered genomic segments. These advances pave the way for the unbiased inclusion of microbial eukaryotes in deciphering determinants of health and disease in the host-associated microbiome.IMPORTANCEMicrobial eukaryotes are common constituents of the human gut where they can contribute to local ecology and host health, but they are often overlooked in microbiome studies. The lack of attention is due to current technical limitations that are heavily biased or poorly recovered DNA from microbial eukaryotes. We developed a method to increase the representation of these eukaryotes in metagenomic sequencing of microbiome samples that allows to improve their detection compared to prior methods and allows for the identification of new species. Application of the technique to gut microbiome samples improved detection of fungi, protists, and helminths. New eukaryotic taxa and their encoded genes could be identified by sequencing a small number of samples. This approach can improve the inclusion of eukaryotes into microbiome research., Competing Interests: M.Z.A. is a board member of the Native BioData Consortium.

The ethics of the scientific study of Ancestors has long been debated by archaeologists, bioanthropologists, and, more recently, ancient DNA (aDNA) researchers. This article responds to the article "Ethics of DNA research on human remains: five globally applicable guidelines" published in 2021 in Nature by a large group of aDNA researchers and collaborators. We argue that these guidelines do not sufficiently consider the interests of community stakeholders, including descendant communities and communities with potential, but yet unestablished, ties to Ancestors. We focus on three main areas of concern with the guidelines. First is the false separation of "scientific" and "community" concerns and the consistent privileging of researcher perspectives over those of community members. Second, the commitment of the guidelines' authors to open data ignores the principles and practice of Indigenous Data Sovereignty. Further, the authors argue that involving community members in decisions about publication and data sharing is unethical. We argue that excluding community perspectives on "ethical" grounds is convenient for researchers, but it is not, in fact, ethical. Third, we stress the risks of not consulting communities that have established or potential ties to Ancestors, using two recent examples from the literature. Ancient DNA researchers cannot focus on the lowest common denominator of research practice, the bare minimum that is legally necessary. Instead, they should be leading multidisciplinary efforts to create processes to ensure communities from all regions of the globe are identified and engaged in research that affects them. This will often present challenges, but we see these challenges as part of the research, rather than a distraction from the scientific endeavor. If a research team does not have the capacity to meaningfully engage communities, questions must be asked about the value and benefit of their research., Competing Interests: J.W. is an associate editor of HGGA., (© 2022 The Authors.)

Genetic datasets lack diversity and include very few data from Indigenous populations. Research models based on equitable partnership have the potential to increase Indigenous participation and have led to successful collaborations. We report here on a meeting of participants in four Indigenous community-university partnerships pursuing research on precision medicine. The goal of the meeting was to define values and practices that strengthen opportunities for genetic research. The group accorded the highest priority to developing trusting relationships, ensuring respect for Indigenous community authority, and pursuing research that has the potential to lead to community benefit. Supporting priorities included incorporation of Indigenous expertise in research planning, transparent communication, and development of community capacity, including capacity to participate in formulating research questions, informing research methodology, and leading research projects. Participants also noted the importance of attention to social determinants of health so that genetic contributors to health are evaluated in the appropriate context.