Prevotella diversity, niches and interactions with the human host

Abstract

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.

Fig. 1 |. Genomic overview of the genus Prevotella.

a | Phylogenetic tree of reference genomes of strains or species of Prevotella and other Prevotellaceae species, with an indication of their ecological niches. The largest number of genomes are associated with human hosts, although Prevotella genomes are also identified in several other host types. Prevotella spp. exhibit variable genome length, ranging from 4.26 Mb for Prevotella copri to 2.37 Mb for Prevotella amnii. Only named species are reported in the tree, which was built using a maximum likelihood approach applied on marker genes. b | Genome characteristics for Prevotella spp. with at least five available genomes. The average number of coding sequences (CDSs) ranges between 2,000 and 3,300. The core size (that is, the number of CDSs that are present in almost all genomes) ranges from 1,200 to 1,900 genes. The pangenome size ranges between 2,600 and 10,400 genes; however, this is partially affected by the number of available genomes (Spearman correlation between genome number and pangenome size of 0.64). Data were generated by whole-genome analysis of currently available Prevotella genomes in public repositories. TABLE 1 and Supplementary Table 1 contain the genomic characteristics of Prevotella spp. considered in this figure and the list of available reference genomes. Numbers in the heat map are in thousands.

Fig. 2 |. Distribution and stratification of Prevotella spp. across human populations and body sites.

Prevalence (part a) and relative abundance (part b) of known Prevotella spp. across four main body sites (that is, the oral cavity (saliva or oral swabs), the skin (cutaneous swabs), the gut (stool samples) and the vagina (vaginal swabs)), five age categories (that is, newborn, child, school-age child, adult and senior) and two main lifestyles (that is, Westernized and non-Westernized). These data were obtained from public repositories of more than 9,500 profiled human metagenomes (curated metadata information is available elsewhere). Quantitative taxonomic profiles were generated with MetaPhlAn 3.0 (REF.). Only named species with a prevalence greater than 0.1% in at least one category are reported. Most species are body-site-specific, and further differences are observed across age categories. The prevalence and relative abundance of Prevotella in the gut (part c) are largely influenced by lifestyle. Non-Westernized populations, which follow a more traditional diet and lifestyle, are enriched in Prevotella spp., and this is consistently observed across countries. Extended heat maps are available in Supplementary Fig. 1.

Fig. 3 |. Current diversity of Prevotella spp. in the human microbiome.

a | A large phylogenetic tree spanning the 56 most prevalent Prevotella species (with at least 20 genomes retrieved from human microbiomes). Isolate sequences were integrated with metagenome-assembled genomes (MAGs) retrieved from more than 10,000 metagenomes and more than 50 human populations. For each species, 15 randomly selected genomes are reported along with the information on the host type (that is, human or mixed sources), the public availability of isolate sequences and the number of retrieved genomes. The tree highlights the gap in strain isolation, with 24 human-associated species that completely lack isolate genomes, the within-species strain diversity and the remarkably well-defined taxonomic species based on the interspecies versus the intraspecies diversity. b | The fraction of Prevotella genomes retrieved from human and non-human hosts (both from isolation and assignment to MAGs) and different human site types suggest multiple ecological patterns. In addition to human-specific species, other species are present in two or more host types. Of note, a few species are ecologically adapted to multiple human body sites, which might also be due to the influx of oral species into the lower gastrointestinal tract. Supplementary Table 1 provides a list of available reference genomes and reconstructed MAGs with their genomic characteristics for the species considered in this figure. NA, not assigned; NHP, non-human primate; SGB, species-level genome bin.

Fig. 4 |. Evidence for a role of Prevotella spp. in human infections and autoimmunity.

a | Network analysis showing the association of each Prevotella species with one or more diseases (grouped into three broad categories: autoimmune diseases, oral infections or other infections) based on a total of 226 studies (see Supplementary BOX 4 for the search and inclusion criteria for the systematic literature review; Supplementary Table 2 includes all the data extracted from the articles included in this work). The thickness of the edges is proportional to the number of articles reporting the involvement of Prevotella spp. in diseases. While some species were specifically associated with one disease group, a few were shared among the three categories. Cases for which species identification was not available are labelled as ‘Prevotella spp.’. The number of the four most abundant Prevotella spp. associated with each detailed disease is shown in Supplementary Fig. 4d. b | Proposed role of Prevotella spp. in human diseases. The percentage of studies for each disease (with at least four studies linking them with Prevotella spp.) are categorized on the basis of the identification method, namely ‘isolation’ (standard microbiology approaches of isolation and cultivation without mechanistic or causative investigation), ‘association’ (low-input or high-input molecular approaches, such as species-specific PCR or 16S rRNA gene sequencing that surveys the presence of bacteria in a sample) and ‘causation’ (studies in which the causative role of Prevotella spp. in the infection was demonstrated in animal models). Most of the studies providing evidence of a link between Prevotella and disease are isolation-based or merely associative. Diseases are ordered on the basis of a descending ‘isolation’ order, and the total number of studies considered per disease is indicated. Supplementary Fig. 2c provides further details of the method used to identify the Prevotella spp. in each disease and extends the results presented here. LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection.