A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections.

Objective: To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens.

Background: Evidence suggests that pathogens originating from the gut microbiota can cause postoperative infection via a process by which they silently travel inside an immune cell and contaminate a remote operative site (Trojan Horse Hypothesis). Here, we hypothesize that Pi-PEG can prevent SSIs in a novel model of postoperative SSIs in mice.

Central catecholaminergic blockade with clonidine prevent SARS-CoV-2 complication: A case series.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a life-threating viral infection that is highly transmissible and be lethal. Although many patients with mild symptoms recover, an acute form of the infection is characterized by rapidly evolving respiratory failure, an acute inflammatory response, organ failure, and death. Herein, we describe the use of clonidine to modulate the acute inflammatory consequences of this infection in three cases.

Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate.

Objective: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.

Design: C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis.

SARS-CoV-2 and the sympathetic immune response: Dampening inflammation with antihypertensive drugs (Clonidine and Propranolol).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a pandemic with the United States now carrying the highest number of cases and fatalities. Although vaccines and antiviral agents are the main focus of therapy, here we present a plausible hypothesis to leverage our understanding of neuroimmunomodulation to intervene in the pathophysiology of the disease to prevent death.

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3.

Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts.

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure.

Sustained Release of Phosphates From Hydrogel Nanoparticles Suppresses Bacterial Collagenase and Biofilm Formation .

Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades intestinal collagen. Antibiotic administration is ineffective in addressing this issue as it inadvertently eliminates normal flora while allowing pathogenic bacteria to "bloom" and acquire antibiotic resistance.

Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.

Objective: The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery.

Background: We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth.

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP.

Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation.

Background: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice.