PMC:7019005 / 29341-33033
Annnotations
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Most notably, all but one study published thus far have involved exclusively rodents, mainly mice (1, 2, 7). The marked difference in the immune-inflammatory response to insults between rodents and humans is well-documented (17). Fundamental differences include, but are not limited to, the divergence of the transcriptomic response, the mismatch of temporal response patterns, differences in both innate and adaptive immunity, and/or the homogeneity of highly inbred mouse strains (18). Pigs, on the other hand, show very similar endotoxin sensitivity and tissue antigenicity, similar cardiovascular and renal physiology including hyperdynamic circulation in sepsis and similar temporal response pattern to humans (19). Additional technical advantages are associated with bigger body size that is comparable to humans and allows extensive instrumentation, continuous monitoring, and serial blood sampling. Moreover, frequent use of specific pathogen-free (SPF) animals in sepsis research, where alterations of the gut microbiome may markedly alter the animal's immune and inflammatory functions and susceptibility to infection, may also contribute to the disconnect between animal studies showing promising drug development and failure to translate to humans. In an interesting recent study a more straightforward comparison of response to anesthesia and surgical trauma was made between conventional and SPF rats (20). Comparison between conventional and SPF animals within one species and even strain (Spraque-Dawley) revealed decreased tolerance to anesthesia, hemodynamic instability, aberrant hematology, traumatic bleeding, and reduced physiological reserve in SPF animals. This altered phenotype to the stress of surgical trauma was completely reversed when SPF animals were returned to the original conventional facility. The role of gut microbiota is another aspect worth consideration when discussing factors potentially affecting the host response to infectious stimulus. It has been demonstrated that variations in the gut microbiota of donor mice influenced clinical as well as molecular phenotype of sepsis (21). At the time of our study, we did not assess individual microbial composition of porcine feces. However, given the single provider of laboratory animals with identical environmental conditions and comparable individual hemodynamic, metabolic, and inflammatory responses to feces, we hypothesize that the putative role of inter-individual variations in fecal microbiota was rather limited in this experiment. Taken together, the genetic and physiological proximity of pigs and humans makes this species an excellent biomodel for translational research, and utilization of domestic (farm) pigs exposed to similar environmental pathogens as humans is clearly superior to mouse models, in which the SPF handling probably limits the clinical translatability even more fundamentally (22, 23).","tracks":[{"project":"TEST0","denotations":[{"id":"32117276-94-100-3576144","span":{"begin":94,"end":96},"obj":"[\"19098906\", \"20558630\", \"22250097\", \"24451364\", \"25986435\", 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