Strain-Level Diversity in the Gut: The P. copri Case
2019; Cell Press; Volume: 25; Issue: 3 Linguagem: Inglês
10.1016/j.chom.2019.02.006
ISSN1934-6069
Autores Tópico(s)Probiotics and Fermented Foods
ResumoIn this issue of Cell Host & Microbe, De Filippis et al., 2019De Filippis F. Pasolli E. Tett A. Tarallo S. Naccarati A. De Angelis M. Neviani E. Cocolin L. Gobbetti M. Segata N. Ercolini D. Distinct genetic and functional traits of human intestinal Prevotella copri strains are associated with different habitual diets.Cell Host Microbe. 2019; 25 (this issue): 444-453Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar report that Prevotella copri strain-level diversity in the gut microbiome can be shaped by host diet. Individual signatures were analyzed by marker gene profiling in assembled pangenomes, providing a strong rationale for the functional adaptation of individual microbial ecosystems in response to diet. In this issue of Cell Host & Microbe, De Filippis et al., 2019De Filippis F. Pasolli E. Tett A. Tarallo S. Naccarati A. De Angelis M. Neviani E. Cocolin L. Gobbetti M. Segata N. Ercolini D. Distinct genetic and functional traits of human intestinal Prevotella copri strains are associated with different habitual diets.Cell Host Microbe. 2019; 25 (this issue): 444-453Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar report that Prevotella copri strain-level diversity in the gut microbiome can be shaped by host diet. Individual signatures were analyzed by marker gene profiling in assembled pangenomes, providing a strong rationale for the functional adaptation of individual microbial ecosystems in response to diet. The human digestive tract is colonized by individually diverse communities of microorganisms, and research in the past decade has identified a fundamental role of this complex microbial ecosystem in the regulation of human health. Community profiling and metagenomic analyses based on high-throughput sequencing indicate that the microbiome can be altered by environmental exposure (e.g., diet and antibiotics) and a variety of host-related conditions (e.g., age and disease). From an ecological standpoint, some of these alterations can be viewed in the context of transient adaptations with a high degree of resilience in the microbiome of a healthy host. However, emerging evidence suggests that persistent perturbations of microbial communities (also often referred to as dysbiosis) are causally linked to a distortion of microbe-host homeostasis, directly affecting the clinical course of a whole variety of immune and metabolic disorders. Nevertheless, and beyond recent enthusiasm, the functional implementation of changes in composition and activity of the microbiome on human health is still in its infancy, and the search for disease-specific signatures is incomplete. One reason for this lack of understanding is the absence of strain-level resolution of microorganisms (Buttó and Haller, 2017Buttó L.F. Haller D. Functional relevance of microbiome signatures: the correlation era requires tools for consolidation.J. Allergy Clin. Immunol. 2017; 139: 1092-1098Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar). One of the two most abundant bacterial phyla of the intestinal microbiota is Bacteroidetes, of which the genera Bacteroides and Prevotella dominate in human populations. Strains of the genus Prevotella have long been believed to be a group of beneficial bacteria associated with plant-rich diet (De Filippis et al., 2016De Filippis F. Pellegrini N. Vannini L. Jeffery I.B. La Storia A. Laghi L. Serrazanetti D.I. Di Cagno R. Ferrocino I. Lazzi C. et al.High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome.Gut. 2016; 65: 1812-1821Crossref PubMed Scopus (836) Google Scholar, Kovatcheva-Datchary et al., 2015Kovatcheva-Datchary P. Nilsson A. Akrami R. Lee Y.S. De Vadder F. Arora T. Hallen A. Martens E. Björck I. Bäckhed F. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella.Cell Metab. 2015; 22: 971-982Abstract Full Text Full Text PDF PubMed Scopus (872) Google Scholar), yet the identification of a single dietary ingredient associated with distinct Prevotella strains is lacking. Other studies suggested Prevotella as a commensal with putative detrimental traits, being linked to rheumatoid arthritis (Scher et al., 2013Scher J.U. Sczesnak A. Longman R.S. Segata N. Ubeda C. Bielski C. Rostron T. Cerundolo V. Pamer E.G. Abramson S.B. et al.Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis.Elife. 2013; 2: e01202Crossref PubMed Google Scholar) and chronic inflammation in HIV-infected patients (Dillon et al., 2016Dillon S.M. Lee E.J. Kotter C.V. Austin G.L. Gianella S. Siewe B. Smith D.M. Landay A.L. McManus M.C. Robertson C.E. et al.Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection.Mucosal Immunol. 2016; 9: 24-37Crossref PubMed Scopus (126) Google Scholar). This functional diversity might indeed result from considerable genetic variation and strain-specific functional plasticity, allowing an efficient intra-species adaptation to environmental changes (Gupta et al., 2015Gupta V.K. Chaudhari N.M. Iskepalli S. Dutta C. Divergences in gene repertoire among the reference Prevotella genomes derived from distinct body sites of human.BMC Genomics. 2015; 16: 153Crossref PubMed Scopus (37) Google Scholar). In this issue of Cell Host & Microbe, De Filippis et al., 2019De Filippis F. Pasolli E. Tett A. Tarallo S. Naccarati A. De Angelis M. Neviani E. Cocolin L. Gobbetti M. Segata N. Ercolini D. Distinct genetic and functional traits of human intestinal Prevotella copri strains are associated with different habitual diets.Cell Host Microbe. 2019; 25 (this issue): 444-453Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar analyzed genetic signatures of Prevotella copri strains extracted from gut metagenomes of healthy Italian adults adopting various dietary habits (vegetarians, vegans, and omnivores). The intra-species functional diversity of P. copri in fecal samples of individual subjects was examined by marker gene profiling in assembled pangenomes using newly developed bioinformatics tools (Segata, 2018Segata N. On the road to strain-resolved comparative metagenomics.mSystems. 2018; 3: e00190-17Crossref PubMed Scopus (67) Google Scholar). Interestingly, while the abundance of P. copri was not different in subjects with the various dietary habits, the authors identified a range of functionally diverse P. copri strains, fueling the hypothesis that strain-level diversity is orchestrated in response to diet. Comparing a dataset of 97 subjects, the genetic signature of P. copri strains in fiber-rich diets was associated with enhanced capabilities of carbohydrate catabolism and fiber degradation, while strains harboring genes involved in branched-chain amino acid (BCAA) biosynthesis were rather associated with omnivore diets. Interestingly, P. copri was suggested to improve glucose metabolism via succinate production from fiber fermentation (De Vadder et al., 2016De Vadder F. Kovatcheva-Datchary P. Zitoun C. Duchampt A. Bäckhed F. Mithieux G. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis.Cell Metab. 2016; 24: 151-157Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar), while another study linked insulin resistance with increased levels of BCAA and the presence of P. copri (Pedersen et al., 2016Pedersen H.K. Gudmundsdottir V. Nielsen H.B. Hyotylainen T. Nielsen T. Jensen B.A. Forslund K. Hildebrand F. Prifti E. Falony G. et al.MetaHIT ConsortiumHuman gut microbes impact host serum metabolome and insulin sensitivity.Nature. 2016; 535: 376-381Crossref PubMed Scopus (1095) Google Scholar). Thus, strain-level diversity stands as an intriguing explanation for putative opposing functional implications in the host. Importantly, De Filippis et al. provide supporting evidence that dietary habits contribute to the selection of effector P. copri strains with diverse functional capacities by comparing the profiled P. copri strains from Italian subjects to published metagenomes of Westernized and non-Westernized populations. The authors identified P. copri strains in non-Western individuals with specific genes required for the breakdown of complex plant polysaccharides, while P. copri strains from Western individuals were enriched in genes encoding proteases typically required for protein degradation. In addition, strains with a capability for folate and vitamin B biosynthesis are enriched in Western populations typically deficient for these micronutrients, again supporting the hypothesis that strain-level diversity co-evolves with dietary exposure. However, it is important to acknowledge that other factors beyond diet (e.g., environment or genetics) might as well contribute to strain-level selection. The comparison of Western and non-Western individuals yielded two main clusters discriminated by 1,368 genes, yet vegetarian and vegan Italian subjects clustered together with Western populations. This observation might be driven by a geographical-based evolution of specific P. copri strains, rationalized beyond diet by a whole variety of possible lifestyle and environmental factors. Collectively, the findings of the study by De Filippis et al. emphasized that strain-resolved metagenomic analyses provide refined clues to the complexity of diet-microbiome adaptations. The inter-individual variation in microbial response to diet implies that intra-species resolution must be considered in assessing the potential of microbial functionality. Connecting strain variants to disease phenotypes or host individualized responses is a crucial step toward understanding the impact of different bacterial strains on host physiology. One avenue of research is to engineer personalized microbial interventions based on the knowledge extracted from comparative strain-level genomics. This remains challenging due to the limited availability of isolates in pure culture. In this context, it seems promising to use a pangenomic-guided approach to broaden the existing, yet limited collection of cultured isolates for further functional evaluation. Genomic information on a particular strain cross-feeding behavior or interaction with co-existing species can provide useful information on culture conditions for novel strain isolation and growth. More studies integrating culture-dependent and strain-level genomic analyses are needed to understand the interaction of bacterial strains and host physiology under different dietary conditions. Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual DietsDe Filippis et al.Cell Host & MicrobeFebruary 21, 2019In BriefThe gut microbiome includes several strains per species, with high genomic diversity. By examining Italian subjects with varying dietary habits, De Filippis et al. demonstrate that diet may select distinctive Prevotella copri strains with distinguishable functions. This diversity may explain subject-specific responses to dietary interventions and variations in human health. Full-Text PDF Open Archive
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