Pathophysiology of the Gut and the Microbiome in the Host Response

Abstract

Objective To describe and summarize the data supporting the “gut” as the motor driving critical illness and multiple organ dysfunction syndrome (MODS) presented at the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26–27, 2015). Data Sources Summary of workshop keynote presentation. Study Selection Not applicable. Data Extraction Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentation and discussion supported and supplemented by relevant literature. Conclusions The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the “motor” of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g. lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to MODS in children.

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].…”

The gut microbiome alters immunophenotype and survival from sepsis

“…Further, intentionally altering the microbiomeby probiotics, fecal microbial transplant, or selective decontamination of the digestive tract-positively effects numerous outcomes in the intensive care unit (20)(21)(22). Together, the transition of a microbiome into a pathobiome has been hypothesized to be a driver of mortality from sepsis (23)(24)(25)(26), at least in part by the ability of invading bacteria to act as antigens and modulate the host immune response (7).…”

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

“…The gut has long been hypothesized to be the "motor" of multiple organ dysfunction (5)(6)(7)(8)(9)(10)(11). Gut epithelial integrity is altered in sepsis, with increased apoptosis, decreased villus length and…”