Gail Cresci

Postoperative Diet Advancement Surgical Dogma vs Evidence-Based Medicine

Postoperative ileus is a natural part of recovery following abdominal and intestinal surgery. Research in the laboratory and clinical arenas has challenged the long-held belief that enteral nutrition (EN) should not be administered until bowel function has resumed, which is typically judged by a subjective bowel function assessment. Traditional postoperative management begins with clinical monitoring of return of bowel function, followed by a clear liquid diet that is advanced to regular solid food as tolerated. Studies have consistently demonstrated that early EN is safe and well tolerated, showing a reduction in wound morbidity and healing, fewer septic complications, diminished weight loss, and improved protein kinetics in patients administered early EN. Barriers to early enteral feeding include fear of GI morbidity, anastomotic disruption or leak but have not been proven valid in clinical or experimental trials. A clear liquid diet is the most frequently ordered first postoperative meal regardless of early or delayed administration. Although generally well tolerated, this diet fails to provide adequate nutrients to the postsurgical patient. In contrast, advancement to a regular diet as the initial meal has been shown to be well tolerated and provides significantly more nutrients than a clear liquid diet. This article reviews basic GI physiology, including motility, nutrient absorption, and the changes that occur in regulation and function of the GI tract following surgery, as well as clinical data regarding postoperative GI function and diet advancement. This will be applied to the clinical practices of postoperative dietary advancement to discuss the timing and choice of initial feeding in the postoperative patient.

Linking Pathogenic Mechanisms of Alcoholic Liver Disease With Clinical Phenotypes.

Alcoholic liver disease (ALD) develops in approximately 20% of alcoholic patients, with a higher prevalence in females. ALD progression is marked by fatty liver and hepatocyte necrosis, as well as apoptosis, inflammation, regenerating nodules, fibrosis, and cirrhosis.(1) ALD develops via a complex process involving parenchymal and nonparenchymal cells, as well as recruitment of other cell types to the liver in response to damage and inflammation. Hepatocytes are damaged by ethanol, via generation of reactive oxygen species and induction of endoplasmic reticulum stress and mitochondrial dysfunction. Hepatocyte cell death via apoptosis and necrosis are markers of ethanol-induced liver injury. We review the mechanisms by which alcohol injures hepatocytes and the response of hepatic sinusoidal cells to alcohol-induced injury. We also discuss how recent insights into the pathogenesis of ALD will affect the treatment and management of patients.

Lactobacillus GG and Tributyrin Supplementation Reduce Antibiotic-Induced Intestinal Injury

BACKGROUND Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes. METHODS C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry. RESULTS Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals. CONCLUSION Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.

Gut Microbiome What We Do and Don’t Know

Within the last decade, research regarding the human gut microbiome has exploded. While the gastrointestinal tract was once regarded simply as a digestive organ, new technologies have led the science world to wonder about the impact that the gut microbiota may have on human health and disease. The gut microbiome is now becoming known for its role in metabolism, immune defense, and behavior. From in utero variations to those that rapidly occur post partum, our gut microbiome changes with age, environment, stress, diet, and health status as well as medication exposure. This article reviews what is currently known regarding various influences on the gut microbiome and is meant to encourage the reader to further explore the unknown.

Tributyrin supplementation protects mice from acute ethanol-induced gut injury.

BACKGROUND Excessive alcohol consumption leads to liver disease. Interorgan crosstalk contributes to ethanol (EtOH)-induced liver injury. EtOH exposure causes gut dysbiosis resulting in negative alterations in intestinal fermentation byproducts, particularly decreased luminal butyrate concentrations. Therefore, in the present work, we investigated the effect of butyrate supplementation, in the form of trybutyrin, as a prophylactic treatment against EtOH-induced gut injury. METHODS C57BL/6J mice were treated with 3 different EtOH feeding protocols: chronic feeding (25 days, 32% of kcal), short-term (2 days, 32%), or acute single gavage (5 g/kg). Tributyrin (0.83 to 10 mM) was supplemented either into the liquid diet or by oral gavage. Intestinal expression of tight junction (TJ) proteins and a butyrate receptor and transporter were evaluated, as well as liver enzymes and inflammatory markers. RESULTS All 3 EtOH exposure protocols reduced the expression and co-localization of TJ proteins (ZO-1, occludin) and the expression of a butyrate receptor (GPR109A) and transporter (SLC5A8) in the ileum and proximal colon. Importantly, tributyrin supplementation protected against these effects. Protection of the intestine with tributyrin supplementation was accompanied by mitigation of EtOH-induced increases in aspartate aminotransferase and inflammatory measures in the short-term and acute EtOH exposure protocols, but not after chronic EtOH feeding. CONCLUSIONS These findings suggest that tributyrin supplementation could serve as a prophylactic treatment against gut injury caused by short-term EtOH exposure.

Genetic resistance to liver fibrosis on A/J mouse chromosome 17.

BACKGROUND Because the histological and biochemical progression of liver disease is similar in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH), we hypothesized that the genetic susceptibility to these liver diseases would be similar. To identify potential candidate genes that regulate the development of liver fibrosis, we studied a chromosome substitution strain (CSS-17) that contains chromosome 17 from the A/J inbred strain substituted for the corresponding chromosome on the C57BL/6J (B6) genetic background. Previously, we identified quantitative trait loci (QTLs) in CSS-17, namely obesity-resistant QTL 13 and QTL 15 (Obrq13 and Obrq15, respectively), that were associated with protection from diet-induced obesity and hepatic steatosis on a high-fat diet. METHODS To test whether these or other CSS-17 QTLs conferred resistance to alcohol-induced liver injury and fibrosis, B6, A/J, CSS-17, and congenics 17C-1 and 17C-6 were either fed Lieber-DeCarli ethanol (EtOH)-containing diet or had carbon tetrachloride (CCl4 ) administered chronically. RESULTS The congenic strain carrying Obrq15 showed resistance from alcohol-induced liver injury and liver fibrosis, whereas Obrq13 conferred susceptibility to liver fibrosis. From published deep sequencing data for chromosome 17 in the B6 and A/J strains, we identified candidate genes in Obrq13 and Obrq15 that contained single-nucleotide polymorphisms (SNPs) in the promoter region or within the gene itself. NADPH oxidase organizer 1 (Noxo1) and NLR family, CARD domain containing 4 (Nlrc4) showed altered hepatic gene expression in strains with the A/J allele at the end of the EtOH diet study and after CCl4 treatment. CONCLUSIONS Aspects of the genetics for the progression of ASH are unique compared to NASH, suggesting that the molecular mechanisms for the progression of disease are at least partially distinct. Using these CSSs, we identified 2 candidate genes, Noxo1 and Nlrc4, which modulate genetic susceptibility in ASH.

Immune-Modulating Formulas Who Wins the Meta-Analysis Race?

Most agree that enteral nutrition is the ideal way to feed critically ill patients who have a functional gastrointestinal tract, but selecting the appropriate enteral formula can be difficult. Specifically, the use of immune-modulating diets has brought much excitement as well as debate. Literature to date presents both positive and potential adverse effects. To aid the clinician in the decision-making process, this article reviews the current research and recommendations regarding the use of immune-modulating diets.

Prophylactic tributyrin treatment mitigates chronic-binge alcohol-induced intestinal barrier and liver injury

Impaired gut‐liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic‐binge ethanol exposure.

Expediting Transition to Home Parenteral Nutrition With Fast-Track Cycling

Background. Delivery of home parenteral nutrition (PN) is typically cycled over 12 hours. Discharge to home on PN is often delayed due to potential adverse events (AEs) associated with cycling PN. The purpose was to determine whether patients requiring long-term PN can be cycled from 24 hours to 12 hours in 1 day instead of 2 days without increasing the risk of PN-related AEs. Methods. Hospitalized patients receiving PN at goal calories infused over 24 hours without severe electrolyte or blood glucose abnormalities were eligible. Patients were randomly assigned to a 1-step “fast-track” protocol or 2-step “standard” protocol. AEs were defined as hypoglycemia or hyperglycemia, new-onset or worsening dyspnea, tachycardia, tachypnea, lower extremity or sacral edema, pulmonary edema, or abdominal ascites and were graded as minor or major. Results. In the 63 patients studied, the most prevalent PN-related AE was hyperglycemia, occurring in 24.2% and 30.0% of patients in the fast-track and standard groups, respectively. Overall, there was no significant difference in the prevalence of PN-related minor AEs between fast-track and standard groups (33.3% and 53.3%, P = .5). No major PN-related AEs occurred in the fast-track group, while 1 major PN-related AE (pulmonary edema) occurred in the standard group. Conclusions. Fast-track cycling is as safe as standard cycling in patients without diabetes mellitus or major organ dysfunction requiring long-term PN. Fast-track cycling could potentially expedite hospital discharge, resulting in decreased healthcare costs and improved patient satisfaction.

Alternative complement pathway component Factor D contributes to efficient clearance of tissue debris following acute CCl4-induced injury

Complement, part of the innate immune system, is involved with immune protection against invading pathogens as well as cell survival and tissue regeneration. It is known that complement activation is required for timely hepatocyte recovery following an acute toxic injury, but which pathway of complement activation is involved in response to hepatocyte injury has not been identified. In these studies we utilize mice deficient in C1qa, C4 and Factor D, lacking the classical, classical/MBL, and alternative pathways of complement activation, respectively, to identify an essential role for Factor D in the ability of the liver to recover from acute toxic injury. Here we demonstrate that following an acute CCl4-induced injury, the involvement of the alternative complement pathway is essential for efficient liver recovery.