Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis.

BACKGROUND: Infectious complications following experimental pancreatitis involve major disruptions in the gut microbiota. The aim of this study was to characterize this disruption by examining the spatioregional distribution in microbial community structure and function following experimental pancreatitis associated with pancreatic infection. METHODS: Mice were subjected to infusion of the pancreatic duct with either taurocholate to induce necrotizing pancreatitis or normal saline (control group). The spatial (lumen versus mucosa) and regional composition and function of the microbiota from the duodenum, ileum, caecum, colon, pancreas and blood were evaluated using 16S rRNA gene amplicon sequencing. RESULTS: Mice that developed necrotizing pancreatitis demonstrated a decrease in microbial richness and significantly altered microbiota in distal parts of the gastrointestinal tract, compared with controls. Among the most differentially increased taxa were the mucus-degrading Akkermansia muciniphila, and there was a decrease of butyrate-producing bacteria following pancreatitis. Application of the SourceTracker tool to the generated metadata indicated that the duodenum was the most probable source of bacteria that subsequently infected pancreatic tissue in this model. The functional prediction annotation using pathway analyses indicated a diminished capacity of the caecal microbiota to metabolize carbohydrate, and fatty and amino acids. DISCUSSION: The distal gut microbiota was significantly impacted in this model of experimental necrotizing pancreatitis. Data suggest that the duodenal microbiota might also play a role in bacterial translation and secondary infections.

Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model.

BACKGROUND: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. METHODS: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. RESULTS: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65-90 per cent for WD versus 4-15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). CONCLUSION: The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice. Surgical relevance Worldwide, enhanced recovery programmes have developed into standards of care that reduce major complications after surgery, such as surgical-site infections and anastomotic leak. A complementary effort termed prehabilitation includes preoperative approaches such as smoking cessation, exercise and dietary modification. This study investigated whether a short course of dietary prehabilitation in the form of a low-fat/high-fibre composition can reverse the adverse effect of a high-fat Western-type diet on anastomotic healing in mice. Intake of a Western-type diet had a major adverse effect on both the intestinal microbiome and anastomotic healing following colonic anastomosis in mice. This could be reversed when mice received a low-fat/high-fibre diet before operation. Taken together, these data suggest that dietary modifications before major surgery can improve surgical outcomes via their effects on the intestinal microbiome.

ANTECEDENTES: Tanto la obesidad como la presencia de cepas bacterianas colagenolíticas (Enterococcus faecalis) pueden aumentar el riesgo de fuga anastomótica. El objetivo de este estudio fue determinar si los ratones alimentados durante un tiempo prolongado con una dieta de tipo occidental con alto contenido en grasas (western type diet, WD) desarrollaban una fuga anastomótica en asociación con una microbiota alterada, así como determinar si una dieta estándar preoperatoria de corta duración baja en grasa/alta en fibra (standard diet, SD) podía mitigar la aparición de fuga. MÉTODOS: Ratones machos C57BL/6 obtenidos de Charles River fueron asignados aleatoriamente a una dieta chow estándar (SD) o a una dieta de tipo occidental obesogénica (WD) durante 6 semanas, seguida de la administración preoperatoria de antibióticos y la realización de una anastomosis en el colon. La microbiota se analizó longitudinalmente después de la operación y se correlacionó con la curación utilizando una puntuación de cicatrización anastomótica ya establecida. En experimentos repetidos, los ratones con una WD durante 6 semanas fueron expuestos a una SD durante 2, 4 y 6 días antes de la cirugía de colon, analizándose la cicatrización de la anastomosis y la microbiota del colon. RESULTADOS: Los ratones alimentados con WD en comparación con los alimentados con SD presentaron un mayor riesgo de fuga anastomótica con un rápido incremento en la abundancia de Enterococcus (65-90% para WD versus 4-15% para SD, P < 0,01). La microbiota de ratones alimentados con SD, pero no con WD, se restableció a su composición preoperatoria después de la operación. La cicatrización anastomótica mejoró significativamente cuando los ratones alimentados con WD fueron expuestos a una dieta SD durante 2 días antes del tratamiento antibiótico y de la cirugía (P < 0,01). CONCLUSIÓN: En ratones, los efectos adversos de una alimentación crónica con una WD sobre la microbiota y la cicatrización anastomótica se pueden prevenir mediante una SD de corta duración.

Bowel preparation under siege.

An analysis of the results and conclusions from the most recent RCTs of the role of mechanical bowel preparation before colonic surgery is presented. The results indicate a wide disparity in the methods, results and conclusion of these studies, and the lack of microbial culture confirmation to advance understanding of how to move the field forward. Controversy on bowel preparation in colorectal surgery.

Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model.

BACKGROUND: Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues. METHODS: Polyphosphorylated polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA-PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed. RESULTS: Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA-PEG20k-Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6-4800-fold (P = 0·008; 5 animals). CONCLUSION: These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.

Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery.

BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery. METHODS: PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome', 'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'. RESULTS: There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself. CONCLUSION: Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

The gut microbiome and the mechanism of surgical infection.

BACKGROUND: Since the very early days of surgical practice, surgeons have recognized the importance of considering that intestinal microbes might have a profound influence on recovery from surgical diseases such as appendicitis and peritonitis. Although the pathogenesis of surgical diseases such as cholelithiasis, diverticulosis, peptic ulcer disease and cancer have been viewed as disorders of host biology, they are emerging as diseases highly influenced by their surrounding microbiota. METHODS: This is a review of evolving concepts in microbiome sciences across a variety of surgical diseases and disorders, with a focus on disease aetiology and treatment options. RESULTS: The discovery that peptic ulcer disease and, in some instances, gastric cancer can now be considered as infectious diseases means that to advance surgical practice humans need to be viewed as superorganisms, consisting of both host and microbial genes. Applying this line of reasoning to the ever-ageing population of patients demands a more complete understanding of the effects of modern-day stressors on both the host metabolome and microbiome. CONCLUSION: Despite major advances in perioperative care, surgeons today are witnessing rising infection-related complications following elective surgery. Many of these infections are caused by resistant and virulent micro-organisms that have emerged as a result of human progress, including global travel, antibiotic exposure, crowded urban conditions, and the application of invasive and prolonged medical and surgical treatment. A more complete understanding of the role of the microbiome in surgical disease is warranted to inform the path forward for prevention.

Lack of evidence for tissue hypoxia as a contributing factor in anastomotic leak following colon anastomosis and segmental devascularization in rats.

PURPOSE: Current surgical dogma dictates that tissue ischemia and hypoxia are major contributing factors in anastomotic leak despite scant evidence. The aim of this study was to determine if tissue hypoxia is a feature of anastomotic leakage in rats following colon resection and segmental devascularization. METHODS: Rats were randomly assigned to undergo sham operation, segmental colon devascularization alone, colectomy alone, or segmental devascularization plus colectomy. Tissue hypoxia present at the colon anastomosis site across the various treatment groups was determined at sacrifice on postoperative day 6. Pimonidazole HCl was injected 30 min prior to sacrifice. Anastomotic tissues were examined and scored for healing versus leakage using an anastomotic healing score (AHS). Collagen content, hypoxia, enteric smooth muscle and periendothelial stromal patterning, and apoptosis were evaluated histologically. RESULTS: No differences in tissue hypoxia were noted in the 16% of anastomotic tissues with poor healing compared to the remaining 84% of rats whose anastomoses healed well. No significant changes were found in cell death in the submucosa of any group. Consistent with previous findings, poor healing was associated with lower collagen content. Submucosal thickness correlated with increased arteriole diameter (R 2 = 0.25, p < 0.005). CONCLUSIONS: These results demonstrate that tissue hypoxia is not a distinctive feature of anastomotic tissues that fail to heal and leak, even when their blood supply is interrupted. These findings suggest that compensatory factors may mitigate the effects of ischemia and hypoxia during healing of anastomotic tissues and that the process of leakage involves factors beyond their acute effects.

Diet creates metabolic niches in the "immature gut" that shape microbial communities.

Although diet composition has been implicated as a major factor in the etiology of various gastrointestinal diseases, conclusive evidence remains elusive. This is particularly true in diseases such as necrotizing enterocolitis where breast milk as opposed to commercial formula appears to confer a "protective effect" to the "immature gut." Yet the mechanism by which this occurs continues to remain speculative. In the present study we hypothesize that the basic chemical composition of diet fundamentally selects for specific intestinal microbiota which may help explain disparate disease outcome and therapeutic direction. Complimentary animal and human studies were conducted on young piglets (21 d.)(n = 8) (IACUC protocols 08070 and 08015) and premature infants (adjusted gestational age 34-36 weeks) (n = 11) (IRB Protocol 15895A). In each study, cecal or stool contents from two groups (Breast milk-fed (BF) vs. Formula-fed (FF)) were analyzed by gas chromatography/mass spectrometry (GC/MS) and comprehensive metabolic profiles generated and compared. Concurrently, bacterial community structure was assayed and respective representative microbiota of the groups determined by 16S rRNA gene amplicon pyrosequencing. Statistical modeling and analysis was done using SIMCA-P+ and R software. GC/MS metabolomics identified clear differences between BF and FF groups in the intestinal environment of piglets and humans. Sugars, amino-sugars, fatty acids, especially unsaturated fatty acids, and sterols were identified as being among the most important metabolites for distinguishing between BF and FF groups. Joint analysis of microbiota and metabolomics pinpointed specific sets of metabolites (p < 0.05) associated with the dominant bacterial taxa. The chemical composition of diet appears to have a significant role in defining the microbiota of the immature gut. Tandem analysis of intestinal microbial and metabolic profiles is potentially a powerful tool leading to better understanding of the role of diet in disease perhaps even leading to specific strategies to alter microbial behavior to improve clinical outcome.

Assessment of binge eating disorder in morbidly obese patients evaluated for gastric bypass: SCID versus QEWP-R.

OBJECTIVE: Binge eating disorder (BED) has been hypothesized to be associated with poor outcome in gastric bypass surgery (GBP). However, past studies have yielded inconsistent results regarding BED and surgical outcome, which may be due to the variety of measures used to assess BED. The present study examines the utility of two commonly used BED diagnostic tools: the Structured Clinical Interview (SCID) and the Questionnaire of Eating and Weight Patterns-Revised (QEWP-R). METHOD: Subjects were 168 adult patients evaluated for GBP. BED was assessed using the SCID and the RESULTS: 27% of the sample received a diagnosis of BED using the QEWP-R, compared with 14% using the SCID. Agreement using Cohen's kappa was 0.37. Compared to sub-non-concordant diagnoses of BED, subjects with concordant diagnoses scored on a measure of self-esteem. DISCUSSION: Although both diagnostic tools use the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria, each yielded different results. Further studies are needed to determine the most accurate method of assessing BED in this population.

Surgical stress shifts the intestinal Escherichia coli population to that of a more adherent phenotype: role in barrier regulation.

BACKGROUND: We have shown that the combination of surgical stress and starvation in mice is associated with a defect in epithelial permeability and increased numbers of mucosa-associated Escherichia coli in the cecum. The aim of this study was to determine the specific role of mucosa-associated E coli on epithelial barrier dysfunction in this model. METHODS: Cecal E coli were harvested from mice 48 hours after a sham operation (control mice) or after a 30% surgical hepatectomy with only water provided ad libitum (short-term starvation) after the surgical procedure. Strains were tested for their ability to adhere to and alter the transepithelial electrical resistance (TEER) of cultured young adult mouse colon epithelial cells. TEER changes were further characterized by mannitol fluxes to confirm a defect in paracellular permeability. RESULTS: Strains of cecal E coli harvested from hepatectomy-starved mice adhered to and altered the permeability of young adult mouse colon cells, whereas E coli from the cecum of control mice were less adherent and had no effect on epithelial permeability. The effect of the strains harvested from mice after hepatectomy on the TEER of young adult mouse colon cells was inhibited by mannose and reversed by ciprofloxacin. CONCLUSION: The combination of surgical stress and short-term starvation is associated with a greater abundance of adherent and barrier-altering strains of E coli in the mouse cecum.

Quality of life and psychosocial adjustment in patients after Roux-en-Y gastric bypass: a brief report.

BACKGROUND: While Roux-en-Y gastric bypass (RYGBP) appears to be the most effective procedure for weight loss in morbidly obese patients, objective outcome data regarding quality of life (QoL) and psychosocial status following surgery are lacking. METHODS: The present study examined the effects of RYGBP in 32 morbidly obese subjects on a variety of outcome measures including QoL and psychosocial functioning. Assessments were conducted before surgery, 1 to 3 weeks post-surgery, and at 6-month follow-up. RESULTS: In addition to weight loss, results show significant improvements in health-related QoL, depression, and self-esteem, as well as a significant reduction in eating pathology following surgery. Results also show that neither the presence of binge-eating disorder nor clinical depression predicted poorer outcome post-surgery. CONCLUSION: RYGBP results in a dramatic reduction in weight, and marked improvements in health-related QoL, depression, self-esteem, and eating pathology, including binge-eating in the short term. These findings need to be replicated in a larger cohort of patients and followed for a longer time before we can reach more definitive conclusions regarding the psychosocial outcome in RYGBP.

Continuous enteral nutrition attenuates pulmonary edema in rats exposed to 100% oxygen.

Adult rats exposed to hyperoxia develop anorexia, weight loss, and a lung injury characterized by pulmonary edema and decreased lung liquid clearance. We hypothesized that maintenance of nutrition during hyperoxia could attenuate hyperoxia-induced pulmonary edema. To test this hypothesis, we enterally fed adult male Sprague-Dawley rats via gastrostomy tubes and exposed them to oxygen (inspired O(2) fraction >0.95) for 64 h. In contrast to controls, enterally fed hyperoxic animals did not lose weight and had smaller pleural effusions and wet-to-dry weight ratios (a measure of lung edema) that were not different from room air controls. Enterally fed rats exposed to hyperoxia had increased levels of mRNA for the Na(+)-K(+)-ATPase alpha(1)- and beta(1)-subunits and glutathione peroxidase. These findings suggest that maintenance of nutrition during an oxidative lung injury reduces lung edema, perhaps by allowing for continued expression and function of protective proteins such as the Na(+)-K(+)-ATPase.

Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa.

OBJECTIVE: To define the putative role of the PA-I lectin/adhesin, a binding protein of Pseudomonas aeruginosa, on lethal gut-derived sepsis after surgical stress, and to determine if this protein is expressed in vivo in response to physical and chemical changes in the local microenvironment of the intestinal tract after surgical stress. SUMMARY BACKGROUND DATA: Previous work from the authors' laboratory has established that lethal gut-derived sepsis can be induced after the introduction of P. aeruginosa into the cecum of mice after a 30% hepatectomy. This effect does not occur when P. aeruginosa is introduced into the cecum of sham operated control mice. Previous experiments further established that the mechanism of this effect is due to the presence of the PA-I lectin/adhesin of P. aeruginosa, which induces a permeability defect to a lethal cytotoxin of P. aeruginosa, exotoxin A. METHODS: Three strains of P. aeruginosa, one lacking functional PA-I, were tested in two complementary systems to assess virulence. Strains were tested for their ability to adhere to and alter the permeability of cultured human colon epithelial cells, and for their ability to induce mortality when injected into the cecum of mice after a 30% hepatectomy. To determine if PA-I is "in vivo expressed" when present in the cecal environment after hepatectomy, strains were retrieved from the cecum of sham-operated and hepatectomy-treated mice 24 and 48 hours after their introduction into the cecum and their PA-I expression was assessed. RESULTS: Results indicated that PA-I plays a putative role in lethal gut-derived sepsis in the mouse, because strains lacking functional PA-I had an attenuated effect on cultured human epithelial cells, and were nonlethal when injected into the cecum of mice after 30% surgical hepatectomy. Furthermore, surgical stress in the form of hepatectomy significantly altered the intestinal microenvironment, resulting in an increase in luminal norepinephrine associated with an increase in PA-I expression in retrieved strains of P. aeruginosa. Co-incubation of P. aeruginosa with norepinephrine increased PA-I expression in vitro, suggesting that norepinephrine plays a role in the observed response in vivo. CONCLUSIONS: Lethal gut-derived sepsis may occur when intestinal pathogens express virulence determinants in response to environmental signals indicating host stress. In this regard, the PA-I lectin/adhesin of P. aeruginosa appears to be a specific example of in vivo virulence expression in colonizing pathogens in the intestinal tract in response to surgical stress.

The key role of Pseudomonas aeruginosa PA-I lectin on experimental gut-derived sepsis.

OBJECTIVE: To examine the effect of Pseudomonas aeruginosa on intestinal barrier function and its lethal potential when introduced into the intestinal tract of mice. SUMMARY BACKGROUND DATA: The mere presence of P. aeruginosa in the intestinal tract of critically ill patients is associated with a threefold increase in death compared with matched cohorts without this pathogen. Whether this effect is a cause or a consequence of the critically ill state has not been previously addressed. METHODS: Transepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells apically inoculated with live P. aeruginosa, exotoxin A, or purified PA-I lectin, an adhesin of P. aeruginosa. Lethality studies to P. aeruginosa were carried out in mice undergoing 30% surgical hepatectomy by injecting the bacteria or its various components directly into the cecum. RESULTS: Only cells exposed to P. aeruginosa or its PA-I lectin developed alterations in barrier function. P. aeruginosa or the combination of PA-I and exotoxin A was lethal to mice when injected into the cecum after partial hepatectomy. Alterations in epithelial barrier function and death in mice were prevented when Pseudomonas was pretreated with N-acetyl D-galactosamine (GalNAc), a binder of PA-I. CONCLUSIONS: P. aeruginosa may act as a pathogen in the gastrointestinal tract, resulting in altered epithelial barrier function and death in a susceptible host. The PA-I lectin of P. aeruginosa may play a key role in its pathogenicity to the intestinal epithelium by inducing a permeability defect to its cytotoxic exoproducts such as exotoxin A.

Surgical stress, bacteria, and mucosal immune function.

Bacteria share a benign coexistence with host mucosal surfaces in the gastrointestinal tract during periods of health. Both host epithelial defense function and bacterial virulence phenotypes are significantly affected by stress. Via discreet and specific sensory input signals to bacteria, the molecular machinery of otherwise commensal strains of bacteria can shift the phenotypes of residential colonizers to more virulent and invasive strains. This occurs at a time when the host may be relatively immunosuppressed by the injury. This adaptive response demonstrates the duplicitous nature of bacteria residing on mucosal surfaces whose ability to shift their virulence characteristics may play an important role in infectious-related morbidity following surgical stress.