The potter's wheel: the host's role in sculpting its microbiota

Abstract

Animals, ranging from basal metazoans to primates, are host to complex microbial ecosystems; engaged in a symbiotic relationship that is essential for host physiology and homeostasis. Epithelial surfaces vary in the composition of colonizing microbiota as one compares anatomic sites, developmental stages and species origin. Alterations of microbial composition likely contribute to susceptibility to several distinct diseases. The forces that shape the colonizing microbial composition are the focus of much current investigation, and it is evident that there are pressures exerted both by the host and the external environment to mold these ecosystems. The focus of this review is to discuss recent studies that demonstrate the critical importance of host factors in selecting for its microbiome. Greater insight into host-microbiome interactions will be essential for understanding homeostasis at mucosal surfaces, and developing useful interventions when homeostasis is disrupted.

Fig. 1

Composition of colonizing bacterial communities at several anatomic surfaces of healthy humans, adapted from Spor et al. [81] with permission. The relative abundances of the six dominant bacterial phyla are based on the analysis of pooled specimens from different body sites. Primary data were from [, –85]. The color designations are: Firmicutes, yellow ( ); Bacteroidetes, green ( ); Fusobacteria, purple ( ); Proteobacteria, black ( ); Cyanobacteria, light green ( ); Actinobacteria, red ( )

Fig. 2

Comparison of microbiota colonizing two species of a basal metazoan, Hydra, adapted from Fraune and Bosch [2] with permission. Analysis of the microbiota of two species, Hydra vulgaris and H. oligactis. The relative abundance of different bacterial divisions within the microbiota is shown in pie charts. Although maintained in the laboratory under standard conditions, including the same diet for more than 20 years, the two species differed dramatically in composition of their microbiota [21]. Analysis also revealed that individuals living in the wild were colonized by a group of microbes similar to that in laboratory-reared counterparts of the same species. The color designations are: α-Proteobacteria, gray ( ); β-Proteobacteria, light blue ( ); δ-Proteobacteria, white ( ); γ-Proteobacteria, black ( ); Spirochetes, pink ( ); Bacteroidetes, green ( )

Fig. 3

Comparison of bacterial taxa composition following reciprocal transplantation of intestinal microbiota in gnotobiotic zebrafish and mice by Rawls et al. [22]. Four intestinal bacterial communities were compared: (right to left) conventionally raised zebrafish (top), ex-germ-free mice that had been colonized with a normal zebrafish microbiota, ex-germ free zebrafish that had been colonized with a normal mouse microbiota, and conventional raised C57BL/6 mice. The relative abundance of different bacterial divisions within these four communities is shown in pie charts. The color designations are: Proteobacteria, black ( ); Firmicutes, yellow ( ); Bacteroidetes, green ( ); Fusobacteria, purple ( ); Actinobacteria, red ( ); Planctomycetes, tan ( ). The tree was based on pairwise differences (weighted UniFrac metric) between the four communities

Fig. 4

Elements of a lactation-mediated nutritive strategy to shape the infant intestinal microbiota, adapted from Zivkovic [29] with permission. a Macronutrient composition of human breast milk, with human milk oligosaccharides (HMOs) as an abundant component at an estimated 5–15 g/L. b HMO-related gene cluster 1 from Bifidobacterium longum subsp. infantis contains the necessary glycosidases (sialidase, fucosidase, galactosidase, and hexosaminidase) and carbohydrate transporters necessary for importing and metabolizing HMOs. c Bifidobacterium longum subsp. infantis imports HMO via specific transporters and the carbohydrates are then hydrolyzed by a collection of intracellular glycosidases, which generate monosaccharides that can enter central metabolic pathways. Interestingly, other infant-borne bifidobacteria possess different strain-specific modes for the consumption of HMOs

Fig. 5

Mucus produced by goblet cells forms a continuous layer in relatively close proximity to the epithelial cell (Epi) surface of the colon. The mucus layer is discontinuous in the small intestine (not shown). In the colon, there is an inner dense layer as well as a less dense region closer to the lumen [40, 41]. The mucus layer provides a physical barrier to limit contact between the lumenal microbes and host cells. In addition, antimicrobial peptides (AMPs) and secretory immunoglobulin A (IgA) are present at the epithelial surface and embedded in mucus. These immunologically active molecules contribute to the barrier function of mucosal surfaces

Fig. 6

Impact of α-defensin and IgA expression on colonizing microbiota. a Analysis of microbiota in small intestine of HD5 transgenic mice, adapted from Salzman et al. [54]. Subclone sequence analysis of the bacterial composition of the distal small intestines of HD5 transgenic mice and their wild-type (WT) littermates, presented as the relative percentage of dominant bacterial phyla. b Analysis of microbiota in the AID^−/− small intestine, adapted from Suzuki et al. [49]. Analysis of mucosal biopsies obtained from proximal segments of the small intestine of 16-month-old AID^−/− and WT mice. Biopsies were pooled from littermates for each genotype, and the microbiota was identified by sequence analyses of the 16S rRNA PCR products. Each color represents a bacterial group identified. AID Activation-induced cytidine deaminase

Fig. 7

Sculpting of the colonizing microbiota. Our central tenet is that the host actively shapes the composition of its colonizing microbiota. The mechanisms include non-immune factors, as well as innate and adaptive immune factors. Together, these host factors combine to create a discriminating environment, provide selective nutrients, and generate specific antimicrobial factors