Invited Review: Ruminal microbes, microbial products, and systemic inflammation1, 2

The ruminal ecosystem is inhabited by complex communities of microbes that include bacteria, protozoa, archaea, fungi, and viruses. The immune system of the animal has evolved to maintain tolerance to innocuous gut commensals and allow the induction of protective responses to pathogens. However, ruminal microbes can also promote local and systemic inflammation. The ruminal epithelium-vascular interface allows absorption of fermentation products and also serves as a selective barrier to prevent translocation and systemic dissemination of bacteria, bacterial toxins, and immunogenic factors. Ruminal dysbiosis that increases ruminal acidity and osmolarity may increase permeability and even induce a breach in the integrity of the epithelial and vascular endothelial barriers, thus facilitating entry of bacteria or bacterial antigens into the portal vein. Upon reaching the liver, bacteria and their products can cause local inflammation and alter function of the organ; if they manage to bypass the liver, they can cause systemic inflammation and affect other organs. Shifts in microbial populations associated with dysbiosis result in increases in concentrations of potentially toxic and inflammatory substances that include lipopolysaccharides, lipoteichoic acids, and leukotoxins, among others. Lipopolysaccharides are constituents of all gram-negative bacteria, which are the dominant ruminal microbes. The entry of lipopolysaccharides into the systemic circulation, either from the rumen or lower gut, could trigger the release of proinflammatory cytokines, reactive oxygen and nitrogen intermediates, and bioactive lipids. An activated immune system drastically increases its demand for nutrients; however, the nutritional requirements of an activated immune system in the context of systemic physiology are still unknown. In conclusion, ruminal microbes and their products generate many complex interactions with the host immune system, and dysbiosis has the potential to induce systemic inflammation. Although inflammation is generally a protective reaction, the persistence of inflammatory mediators could have negative consequences for the host.