The Gut Microbiome and Its Potential Role in the Development and Function of Newborn Calf Gastrointestinal Tract

Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

The temporal sequence of microbial establishment in the rumen of the neonatal ruminant has important ecological and pathophysiological implications. In this study, we characterized the rumen microbiota of pre-ruminant calves fed milk replacer using two approaches, pyrosequencing of hypervariable V3-V5 regions of the 16S rRNA gene and whole-genome shotgun approach. Fifteen bacterial phyla were identified in the microbiota of pre-ruminant calves. Bacteroidetes was the predominant phylum in the rumen microbiota of 42-day-old calves, representing 74.8% of the 16S sequences, followed by Firmicutes (12.0%), Proteobacteria (10.4%), Verrucomicrobia (1.2%) and Synergistetes (1.1%). However, the phylum-level composition of 14-day-old calves was distinctly different. A total of 170 bacterial genera were identified while the core microbiome of pre-ruminant calves included 45 genera. Rumen development seemingly had a significant impact on microbial diversity. The dazzling functional diversity of the rumen microbiota was reflected by identification of 8298 Pfam and 3670 COG protein families. The rumen microbiota of pre-ruminant calves displayed a considerable compositional heterogeneity during early development. This is evidenced by a profound difference in rumen microbial composition between the two age groups. However, all functional classes between the two age groups had a remarkably similar assignment, suggesting that rumen microbial communities of pre-ruminant calves maintained a stable function and metabolic potentials while their phylogenetic composition fluctuated greatly. The presence of all major types of rumen microorganisms suggests that the rumen of pre-ruminant calves may not be rudimentary. Our results provide insight into rumen microbiota dynamics and will facilitate efforts in formulating optimal early-weaning strategies. Published 2011. This article is a US Government work and is in the public domain in the USA.