Abstract
Many colonic mucosal genes that are highly regulated by microbial signals are differentially expressed along the rostral-caudal axis. This would suggest that differences in regional microbiota exist, particularly mucosa-associated microbes that are less likely to be transient. We therefore explored this possibility by examining the bacterial populations associated with the normal proximal and distal colonic mucosa in context of host Toll-like receptors (TLR) expression in C57BL/6J mice housed in specific pathogen-free (SPF) and germ-free (GF) environments. 16S rRNA gene-based terminal restriction fragment length polymorphism (T-RFLP) and clone library analysis revealed significant differences in the community structure and diversity of the mucosa-associated microbiota located in the distal colon compared to proximal colon and stool, the latter two clustering closely. Differential expression of colonic TLR2 and TLR4 along the proximal-distal axis was also found in SPF mice, but not in GF mice, suggesting that enteric microbes are essential in maintaining the regional expression of these TLRs. TLR2 is more highly expressed in proximal colon and decreases in a gradient to distal while TLR4 expression is highest in distal colon and a gradient of decreased expression to proximal colon is observed. After transfaunation in GF mice, both regional colonization of mucosa-associated microbes and expression of TLRs in the mouse colon were reestablished. In addition, exposure of the distal colon to cecal (proximal) microbiota induced TLR2 expression. These results demonstrate that regional colonic mucosa-associated microbiota determine the region-specific expression of TLR2 and TLR4. Conversely, region-specific host assembly rules are essential in determining the structure and function of mucosa-associated microbial populations. We believe this type of host-microbial mutualism is pivotal to the maintenance of intestinal and immune homeostasis.
Highlights
The mammalian colon is home to a unique ecosystem of trillions of microorganisms that generally live in harmony with the host and serve important physiological functions [1,2,3]
It is well known that many types of host gene expression in the colonic mucosa are highly regulated by microbial signals, including intestinal epithelial heat shock proteins [8], RELM-beta [9], and the vitamin D receptor [10]
The difference was significant comparing the distal colon to the other samples (n = 24, p,0.05) in all litters, but there were no significant differences in richness between the proximal colon and stool sample
Summary
The mammalian colon is home to a unique ecosystem of trillions of microorganisms that generally live in harmony with the host and serve important physiological functions [1,2,3]. Hundreds of microbial species are present both within the colonic lumen and closely associated with the mucosa While both populations are believed to be important to host physiology, mucosa-associated microbiota, which intimately contact and interact with the host, are likely to be especially pivotal to functions such as immune activation, angiogenesis, epithelial growth and development, gene expression and mucus production [4,5,6,7]. Few studies have distinguished between luminal and mucosa-associated microbes of the mammalian colon or have examined how mucosa-associated microbiota is related to regional host responses or gene expression Many of these genes are differentially expressed along the rostral-caudal axis of the mammalian colon, presumably to serve unique functions inherent to that region. This may have affected both luminal and mucosaassociated microbiota, skewing them to appear less diverse and more homogeneous throughout the length of the colon
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