Overview of Breath Testing in Clinical Practice in North America.

Human breath is an easily, noninvasively obtained substance. It offers insight into metabolism and is used to diagnose disaccharide malabsorption, infection, small bowel bacterial over growth, and transit times. Herein, we discuss the readily available clinical breath tests, how they function, how they are administered and interpreted and some pitfalls in their use.

Secreted phosphoglucose isomerase is a novel biomarker of nonalcoholic fatty liver in mice and humans.

The current gold standard for diagnosis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is through a liver biopsy, and there is an urgent need to develop non-invasive methods for early detection. We previously demonstrated metabolic remodeling in the mouse fatty liver, which is marked by increased hepatic expression and activities of phosphoglucose isomerase (PGI) and several other glycolytic enzymes. Since PGI is actively transported out of the cell, acting as a multifunctional cytokine referred to as autocrine motility factor (AMF), we explored the possibility that PGI secreted from the fatty liver may be targeted for early detection of the silent disease. We report here that mice with NASH exhibited significantly elevated serum PGI enzyme activities compared to normal control (P < 0.005). We further confirmed the finding using serum/plasma samples (n = 73) collected from a cohort of NASH patients who were diagnosed according to Kleiner's criteria, showing a normal mean PGI of 19.5 ± 8.8 IU/L and patient mean PGI of 105.6 ± 79.9 IU/L (P < 0.005). In addition, elevated blood PGI in NASH patients coincided with increased blood L-lactate. Cell culture experiments were then conducted to delineate the PGI-lactate axis, which revealed that treatment of HepG2 cells with recombinant PGI protein stimulated glycolysis and lactate output, suggesting that the disease-induced PGI likely contributed to the increased lactate in NASH patients. Taken together, the preclinical and clinical data validate secreted PGI as a useful biomarker of the fatty liver that can be easily screened at the point of care.

Cystic Fibrosis-related Liver Disease: The Next Challenge.

Up to 40% of individuals with cystic fibrosis have cystic fibrosis-related liver disease (CFLD); however, only 5% to 10% will have clinically evident disease. With the introduction of powerful cystic fibrosis transmembrane conductance regulator (CFTR) enhancers, effective treatment for cystic fibrosis is available. The role of CFTR enhancers in liver disease is unknown at this time. The traditionally accepted theory of the pathogenesis of CFLD is being questioned. A different pathogenesis may lead to new ways to treat CFLD. The way that CFLD is diagnosed and monitored is evolving as new imaging technology become available.

Gut Microbiota and Liver Injury (II): Chronic Liver Injury.

Chronic liver injury mainly comprises viral hepatitis, fatty liver disease, autoimmune hepatitis, cirrhosis and liver cancer. It is well established that gut microbiota serves as the key upstream modulator for chronic liver injury progression. Indeed, the term "gut-liver axis" was mostly applied for chronic liver injury. In the current chapter, we will summarize the relationship between gut microbiota and chronic liver injury, including the interaction between them based on latest clinic and basic research.

Celiac Disease Nutritional Status and Poor Adherence to Follow-up.

Introduction. Celiac disease, an autoimmune enteropathy, occurs in susceptible individuals and is treatable with a gluten-free diet. These may not be supplemented with vitamins. Objective. To assess the nutritional health of children who have biopsy-proven celiac disease. Methods. Charts were reviewed between July 1, 2007, and June 30, 2017. Results. A total of 252 children ages 0 to 21 years had biopsy-proven celiac disease, mean age 11 ± 4.1 years. Body mass index Z-score was 0.2 ± 1.2 at diagnosis. Except for vitamin D, few had deficiencies at diagnosis. At 1-year follow-up, there was no significant change in anthropomorphics or vitamin status. Adherence to follow-up was poor; at 5 years after diagnosis, 39% adhered to follow-up. Conclusion. Despite a rigorous, proactive protocol for contacting and following children with celiac disease, adherence to follow-up was poor. New strategies, such as follow-up through the primary care provider, are needed.

Difference in Pathomechanism Between Crohn's Disease and Ulcerative Colitis Revealed by Colon Transcriptome.

BACKGROUND: We aim to identify the differences in colonic mucosal transcriptome between Crohn's disease (CD) and ulcerative colitis (UC) for a better understanding of the molecular pathology. METHODS: Differentially expressed genes (DEG) in the colonic mucosa of CD and UC were identified with a global gene expression microarray dataset generated from the colon biopsies of CD and UC patients and normal controls. The DEGs were then processed to identify altered pathways and modularized DEGs and pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis with an independent cohort of samples was performed to validate the microarray data. RESULTS: At the pathway level, virus infection and autoimmune pathways were upregulated in CD but not in UC when compared with controls. Some of the relevant DEGs (such as TAP1 and TAP2) were elevated in both CD and UC, with CD exhibiting more pronounced elevations. Gene expression levels in viral infection pathways were correlated with those of autoimmune pathways. In contrast, pattern recognition-mediated innate immune pathways (TLR4 and TLR2) were significantly elevated in UC but not in CD. Similar results were observed with an independent cohort by qRT-PCR. CONCLUSIONS: Our data support the hypothesis that viral infection induced autoimmunity may represent a pathomechanism for IBD, especially CD. However, pattern recognition-mediated innate immunity targeting microbiome may play a more important role in UC compared with CD. Our findings identified different intervention targets for CD and UC, which may lead to more effective treatments for IBD patients.

Effectiveness of Colonic Fluid Resuscitation in a Burn-Injured Swine.

To determine the effectiveness of colonic fluid absorption as a route for fluid resuscitation of a major burn. In order to assess the feasibility and performance of colonic resuscitation, the authors compared plasma volume expansion and hemodynamic parameters of animals submitted to colonic or intravenous fluid resuscitation. Twelve anesthetized swine were submitted to a 40% full thickness flame burn. Thirty minutes later fluid resuscitation was initiated with either intravenous or colonic infusion of crystalloid based on the Parkland formula. This treatment lasted 4.5 hours. The volume of fluid infused was 86 ± 18 ml/kg for the intravenous treatment and 89 ± 14 ml/kg for the colonic treatment. The percentage of fluid absorbed by the colon at the end of the protocol was 30 ± 13% of the infused fluid. Enteral resuscitation was equally effective in expanding plasma volume at the end of the protocol. Laboratorial and hemodynamic parameters were similar between the two resuscitation strategies throughout the study. Urine output was significantly higher in the intravenous group (7.9 ± 4.2 ml/kg/hr vs 0.9 ± 0.3 ml/kg/hr, P = .03). This study demonstrates that colonic infusion of normal saline in a severe burn injury model can restore hemodynamic stability and expand plasma volume to a degree that rivals the effect of direct intravenous infusion for early burn resuscitation in a swine model.

Bile Acids and the Gut Microbiome as Potential Targets for NAFLD Treatment.

Semisynthetic bile acid (BA) obeticholic acid, a potent farnesoid X receptor (FXR) agonist, exhibited beneficial effects on nonalcoholic fatty liver disease (NAFLD). Obeticholic acid, however, did not cause a resolution of nonalcoholic steatohepatitis. Here we discuss several prominent knowledge gaps in BA/FXR biology. Firstly, although many groups reported elevated serum BA levels, there are reports of decreased or normal serum BA levels in NAFLD, underlining the complexity of BA regulation by environmental and genetic factors. Secondly, conflicting data exist in animal studies regarding the effects of FXR signaling on obesity and associated metabolic abnormalities. Thirdly, it remains obscure how the gut microbiome and the BA pool interact and influence the pathogenesis of NAFLD. Lastly, it is not known how FXR-mediated signaling interact with G protein-coupled BA receptor 1-mediated signaling. Answering these questions may lead to an improved pharmaceutical intervention for NAFLD targeting the FXR signaling pathway.

Anemia in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Anemia is the most frequent extra-intestinal finding in inflammatory bowel disease (IBD). The aim of this study is to determine the prevalence and types of anemia in pediatric patients with IBD at diagnosis and at approximately 1 year follow-up. METHODS: This is a retrospective chart review of patients diagnosed with IBD from 2005 to 2012, ages 1 to 18 years. Patients who had hemoglobin, hematocrit, mean corpuscular volume, and iron indices obtained at the time of diagnosis and at approximately 1 year follow-up were included in the study. The prevalence of anemia at the beginning and the end of the study was recorded. Using the soluble transferrin receptor index the type of anemia was determined. RESULTS: At diagnosis, 67.31% of patients were anemic. Overall, 28.85% of patients had either iron deficiency anemia (IDA) or a combination of IDA and anemia of chronic disease (ACD), whereas 38.46% had ACD alone. At follow-up, 20.51% were anemic. 15.38% had either IDA or a combination of IDA and ACD; 5.13% had ACD alone. The pattern of anemia and response to therapy differed among the IBD phenotypes CONCLUSIONS:: Anemia is frequent in inflammatory bowel disease. The prevalence was higher in Crohn disease (CD). At 1 year, the prevalence of anemia decreased significantly, but persisted. Anemia of chronic disease predominated in CD. Iron deficiency anemia continued to be present in CD and ulcerative colitis.

Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis.

A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.