The Shift of an Intestinal “Microbiome” to a “Pathobiome” Governs the Course and Outcome of Sepsis Following Surgical Injury

Abstract

Sepsis following surgical injury remains a growing and worrisome problem following both emergent and elective surgery. Although early resuscitation efforts and prompt antibiotic therapy have improved outcomes in the first 24–48 hours, late onset sepsis is now the most common cause of death in modern intensive care units. This time shift may be, in part, a result of prolonged exposure of the host to the stressors of critical illness which, over time, erode the health promoting intestinal microbiota and allow for virulent pathogens to predominate. Colonizing pathogens can then subvert the immune system and contribute to the deterioration of the host response. Here we posit that novel approaches integrating the molecular, ecological and evolutionary dynamics of the evolving gut microbiome/pathobiome during critical illness are needed to understand and prevent the late onset sepsis that develops following prolonged critical illness.

Myosin Light Chain Kinase Knockout Improves Gut Barrier Function and Confers a Survival Advantage in Polymicrobial Sepsis

“…In contrast, the finding that intestinal epithelial apoptosis was not different between septic WT and MLCK -/-mice makes it unlikely that normalization of intestinal barrier function in knockout mice was directly related to epithelial cell death. Further, quantitative cultures of peritoneal fluid and blood were similar in WT and MLCK -/-mice, suggesting that bacterial burden alone was not responsible for differences in barrier function, although we cannot rule out the possibility that the microbiome was more virulent in WT mice (24,54), leading to more invasive bacteria -and hence hyperpermeability -in the absence of differences in bacterial numbers. Hyperpermeability induced by CLP in WT mice is associated with increases in jejunal claudin 2 and JAM-A as well advantage was associated with a significant decrease in systemic IL-10 but was not accompanied by a decrease in either local or distant bacterial burden.…”

“…Notably, sepsis induces intestinal hyperpermeability (18)(19)(20)(21). While early studies in critical illness hypothesized that gut barrier damage induces sepsis by translocation of intact bacteria, the reality has turned out to be considerably more complex (7,(22)(23)(24). The intestine acts as a selective barrier, preventing movement of potentially damaging microbes, toxins and antigens from the gut lumen, while simultaneously allowing paracellular movement of water, solutes and immune-modulating factors (25)(26)(27).…”

Surviving sepsis campaign: research priorities for sepsis and septic shock

“…Whereas the most common microbe makes up 25% of the microbiome in healthy patients, a massive diversity crash causes results in the most common microbe making up 95% of the microbiome in ICU patients [215]. These changes appear to result from both the underlying disorder (sepsis) and its treatment (antibiotics), which by definition alter the microbiome [216][217][218][219][220][221][222]. Further, microbes alter their virulence in response to both the internal host environment (availability of phosphate) and treatments in critically ill patients (opiates) [223][224][225].…”

On the Importance of the Microbiome and Pathobiome in Coral Health and Disease

“…This new term has been used to describe the complex interactions of pathogenic microbes which may influence or drive disease processes and their relationship to the "normal" microbiome of the organism in question (Chow et al, 2011;Vayssier-Taussat et al, 2014). Both terms are now widely used throughout the literature, particularly in the medical domain, for example with respect to the human gut (Huttenhower and Human Microbiome Project Consortium, 2012;Krezalek et al, 2015;Lloyd-Price et al, 2016). However, these terms are less widely used in the environmental sciences, and studies focused on Scleractinian corals for example have more commonly utilized the terms "microbiota" or "microbial associates" to describe the microbial communities associated with these hosts.…”