Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium

A Novel Secretion Pathway of Salmonella enterica Acts as an Antivirulence Modulator during Salmonellosis

Salmonella spp. are Gram-negative enteropathogenic bacteria that infect a variety of vertebrate hosts. Like any other living organism, protein secretion is a fundamental process essential for various aspects of Salmonella biology. Herein we report the identification and characterization of a horizontally acquired, autonomous and previously unreported secretion pathway. In Salmonella enterica serovar Typhimurium, this novel secretion pathway is encoded by STM1669 and STM1668, designated zirT and zirS, respectively. We show that ZirT is localized to the bacterial outer membrane, expected to adopt a compact β-barrel conformation, and functions as a translocator for ZirS. ZirS is an exoprotein, which is secreted into the extracellular environment in a ZirT-dependent manner. The ZirTS secretion pathway was found to share several important features with two-partner secretion (TPS) systems and members of the intimin/invasin family of adhesions. We show that zirTS expression is affected by zinc; and that in vivo, induction of zirT occurs distinctively in Salmonella colonizing the small intestine, but not in systemic sites. Additionally, strong expression of zirT takes place in Salmonella shed in fecal pellets during acute and persistent infections of mice. Inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host–pathogen balance during salmonellosis

An Examination of Diet for the Maintenance of Remission in Inflammatory Bowel Disease

Diet has been speculated to be a factor in the pathogenesis of inflammatory bowel disease and may be an important factor in managing disease symptoms. Patients manipulate their diet in attempt to control symptoms, often leading to the adoption of inappropriately restrictive diets, which places them at risk for nutritional complications. Health professionals struggle to provide evidence-based nutrition guidance to patients due to an overall lack of uniformity or clarity amongst research studies. Well-designed diet studies are urgently needed to create an enhanced understanding of the role diet plays in the management of inflammatory bowel disease. The aim of this review is to summarize the current data available on dietary management of inflammatory bowel disease and to demonstrate that dietary modulation may be an important consideration in managing disease. By addressing the relevance of diet in inflammatory bowel disease, health professionals are able to better support patients and collaborate with dietitians to improve nutrition therapy.Arts and Sciences, Irving K. Barber School of (Okanagan)Biology, Department of (Okanagan)ReviewedFacult

Dietary Fatty Acids and Host–Microbial Crosstalk in Neonatal Enteric Infection

Human milk is the best nutritional choice for infants. However, in instances where breastfeeding is not possible, infant formulas are used as alternatives. While formula manufacturers attempt to mimic the performance of human breast milk, formula-fed babies consistently have higher incidences of infection from diarrheal diseases than those breastfed. Differences in disease susceptibility, progression and severity can be attributed, in part, to nutritional fatty acid differences between breast milk and formula. Despite advances in our understanding of breast milk properties, formulas still present major differences in their fatty acid composition when compared to human breast milk. In this review, we highlight the role of distinct types of dietary fatty acids in modulating host inflammation, both directly and through the microbiome-immune nexus. We present evidence that dietary fatty acids influence enteric disease susceptibility and therefore, altering the fatty acid composition in formula may be a potential strategy to improve infectious outcomes in formula-fed infants.Arts and Sciences, Irving K. Barber School of (Okanagan)Medicine, Faculty ofBiology, Department of (Okanagan)Medicine, Department ofReviewedFacult

Human behavior, not race or geography, is the strongest predictor of microbial succession in the gut bacteriome of infants

Colonization of the gastrointestinal tract with microorganisms during infancy represents a critical control point for shaping life-long immune-mediated disease susceptibility. Abnormal colonization or an imbalance of microbes, termed dysbiosis, is implicated in several diseases. Consequently, recent research has aimed at understanding ways to manipulate a dysbiotic microbiome during infancy to resemble a normal, healthy microbiome. However, one of the fundamental issues in microbiome research is characterizing what a “normal” infant microbiome is based on geography, ethnicity and cultural variations. This review provides a comprehensive account of what is currently known about the infant microbiome from a global context. In general, this review shows that the influence of cultural variations in feeding practices, delivery modes and hygiene are the biggest contributors to microbial variability. Despite geography or race, all humans have similar microbial succession during infancy

Correction: Brown, K., et al. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease. Nutrients 2012, 4, 1095–1119

We have found following errors in paper [1] which has been published in Nutrients, the following references should be cited as

Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

The gastrointestinal (GI) microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.Arts and Sciences, Irving K. Barber School of (Okanagan)Biology, Department of (Okanagan)ReviewedFacult

Omega-3 polyunsaturated fatty acid supplementation during the pre and post-natal period: A meta-analysis and systematic review of randomized and semi-randomized controlled trials

Background & Aims: Long chain omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA) are widely considered beneficial for infant health and development. The aim of this meta-analysis was to summarize the evidence related to the clinical outcomes of long chain n-3 PUFA supplementation maternally and in fortified formula/taken directly. Additionally, we investigate if the addition of arachidonic acid (AA) alters the effects caused by n-3 PUFA supplements. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (1974 to June 2015) CINAHL (1990 to June 2015), PubMed (1966–2015), Web of Science (1864–2015), MEDLINE (1974 to June 2015), and hand searches for randomized and semi-randomized controlled trials on term infants evaluating the effects of long chain n-3 PUFA supplementation taken maternally and in milk based formula or directly. Results: We identified 39 formula and 39 breastmilk studies on the clinical outcomes of long chain n-3 PUFA supplementation, with or without AA, on infant immunity and development. Of these studies, 32 formula and 37 breastmilk studies were deemed appropriate resulting in a total of 2443 formula fed infants and 4553 breastfed infants exposed to n-3 PUFA supplementation. This meta-analysis shows that n-3 PUFA supplementation in infants delivered either maternally or in formula/directly, does not improve visual acuity, language development, or cognition. However, some aspects of growth, motor development, behavior and cardiovascular health are differentially altered in the summary effects of certain studies with the more desired effect occurring often in breastfed infants compared to formula fed infants. Moreover, this meta-analysis shows that n-3 PUFA supplements affects infant immune development and reduces pro-inflammatory responses in the supplemented breastfed and fortified formula fed/directly supplemented infants. Conclusion: Overall, the evidence does not support the continued supplementation of infant formula with long chain n-3 PUFA considering the negative impact on the developing immune responses