Diversity Profile And Phylo-functional Core Of The Mammalian Gut Microbiota—With Healthy Human And Giant Panda As Models

Mammals have been living on this planet for millions of years. To adapt to the extensive changes in the Earth’s climate and environment including grasslands expansion during such a lengthy period, the ancestral meat-eating mammalian lineages underwent massive evolutionary radiation into myriad habitats many times, by altering their foraging behavior, diet and digestive system systematically, from carnivorous to herbivorous. Most herbivores have evolved specialized, enlarging parts of their gut(such as foregut and hindgut) to prolong the retention times of the cellulose-rich digesta and to accommodate extremely diverse microbial specialists for efficient and thorough degredation of the recalcitrant plant materials. The mammals and their indigenous gut microbial communities have coevolved intricate and intimate mutual relationships, resulting in the concept of “Supraorganism”. On the one hand, diet, gut morphology and physiology largely shape both the composition and function of mammalian gut microbiota. On the other hand, gut microbiota provides a great deal of metabolic functions that are not encoded in their hosts’ own genomes, which can have either beneficial(such as vitamin systhesis and short-chain fatty acid(SCFA) production) or deleterious(such as the release of endotoxins) effects on the health of their hosts. If the gut microbiota are indispensable to the host’s well being, healthy mammalian individuals may share some key structural features to constitute a phylogenetic core of gut microbiota. Here, we use two disparate mammalian species as supraorganismal models to explore the core gut microbiota of healthy mammals, and its potential contribution to the host health.We first focused on healthy young human individuals. The human gut microbiota shows typical characteristics of those of omnivorous primates, such as an intermediate level of microbial diversity compared with carnivores and herbivores. Substantial inter-individual variations were repeatedly observed in the diversity and structure of healthy human gut microbiota, but the intra-individual fluctuations across time are minimal. However, it is still unclear which roles these variations play in human health and which factors contribute to them. It also remains to reveal whether healthy human individuals can commonly share some features in their gut microbiota despite these heterogeneities. We thus performed a cross-sectional study of the gut microbiota structure of 20 Chinese cohorts encompassing only healthy individuals in young adulthood, from 7 ethnic groups residing in rural and urban regions in 9 provinces throughout China(n = 314). Structural profiling of the gut microbiota of these cohorts revealed their significant segregation, which could be primarily attributed to ethnicity/geography. The impact of rural/urban lifestyle on the gut microbiota structure varied widely across geography and ethnicity. Regardless of the remarkable differentiation of the gut microbiota across these cohorts, nine predominant bacterial genera(i.e., Phascolarctobacterium, Roseburia, Bacteroides, Blautia, Faecalibacterium, Clostridium, Subdoligranulum, Ruminococcus and Coprococcus, collectively representing nearly half of the total sequences) co-occurred in all the individuals. All of these nine core genera are known to contain SCFA-producing members, suggesting they may provide convergent and essential ecosystem services to maintain human health. Moreover, the exact composition of this genus-level phylogenetic core was still significantly associated with ethnicity/geography and lifestyle. Therefore, both the host-related and environmental factors do strongly influence the healthy young human gut microbiota, but the persistence of the phylo-functional core with provision of potentially conserved and essential “ecosystem services” for human health may also represent a common feature of the healthy human gut microbiota.Compared with human beings, the understanding of the gut microbiota of other mammalian species is still relatively limited. Because of the importance of diet, gut morphology and physiology in shaping gut microbiota, it is necessary to investigate the mammalian “outliers” with unusual diets and gut morphology. The giant panda may represent a typical example of these outliers, but remains poorly studied. It evolved from omnivorous bears, but it has been living as an exclusively bamboo-consuming species for millions years. It still retains a typical carnivorous digestive system, with the lack of any enzymes for bamboo digestion encoded in its genome. To determine whether similar adaptation of the gut microbiota to the highly fibrous diet occurs in this animal as in many other herbivores, we conducted a longitudinal structural profiling of the captive giant panda fecal microbiota(n = 45) in spring, summer and late autumn within one year. This population manifested striking intra-individual variations in the diversity and structure of gut microbiota across seasons, which even exceeded the variations between different individuals. Compared with 124 gut microbiota profiles from 54 mammalian species investigated previously, all these giant pandas, together with other 9 captive and 7 wild individuals, showed a poor level of gut microbiota diversity. The overall structure of their gut microbiota was entirely differentiated from those of non-panda herbivores, but converged with most of its carnivorous and omnivorous relatives. This carnivore-like structure of the giant panda gut microbiota included three primary features. Firstly, the giant panda gut microbiota showed deficiency in putative cellulolytic phylotypes that are typically enriched in other non-panda herbivores(e.g., lineages from Ruminococcaceae and Bacteroides). Secondly, it was predominated by Gram-negative, facultative Escherichia/Shigella and Streptococcus, with only Escherichia/Shigella as the “core” member. Thirdly, members belonging to class Clostridia were common and abundant in the giant panda gut microbiota, but most of them were absent in other non-panda herbivores and did not have strong phylogenetic relations with known cellulolytic Clostridium-related lineages. Therefore, the carnivore-like gut microbiota and digestive system of the giant panda suggest a poor support for its highly fibrous diet.Taken together, our microbiome-wide association studies(Mi WAS) unraveled that both healthy human and giant panda harbor mammalian species-specific, genus-level core gut microbiota. However, such phylogenetic core appears to provide distinctive ecosystem services for the host health in human and the giant panda, which shed light on the understanding of host-microbiota co-evolutionary fitness at the supraorganismal level.