Editorial Gastrointestinal Inflammation and Repair: Role ...downloads.hindawi.com/journals/grp/2016/6516708.pdf · H. pylori CagA and IL- . Gastric cancer is the rd cause of cancer

EditorialGastrointestinal Inflammation and Repair:Role of Microbiome, Infection, and Nutrition

Helieh S. Oz,1 Sung-Ling Yeh,2 and Manuela G. Neuman3

1University of KY Medical Center, Lexington, KY, USA2School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan3University of Toronto and In Vitro Drug Safety and Biotechnology, Toronto, ON, Canada

Correspondence should be addressed to Helieh S. Oz; [email protected]

Received 25 October 2016; Accepted 26 October 2016

Copyright © 2016 Helieh S. Oz et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gastrointestinal inflammation is a complex biological respo-nse to injury as a result of different stimuli such as pathogens,damaged cells, or irritants. Symbiotic microbiome in diges-tive tract is considered to protect gut by removing harmfulstimuli and to enhance healing process. Alteration or absenceof microbiome can lead to exacerbated type 2 immunity andallergic/infectious and inflammatory complications includ-ing parasitic diseases. Thus, the microbiota regulates type 2responses and acts as a key element in harmonizing immuneresponses at mucosal surfaces. While the mechanism bywhich microbiota regulates type 2 immunity is unclear, it isknown as a strong inducer of proinflammatory T helper 17cells and regulatory T cells (Tregs) in the intestine.The signalsat the sites of inflammation mediate rapid cell recruitmentand differentiation in order to remove inflammatory inducersand promote tissue homeostasis restoration.However, persis-tent inflammatory stimuli or dysregulation of mechanisms ofthe restoration can lead to chronic inflammation. Differentstressors can affect immune system and increase risk forinfectious diseases, such as gastritis in postinfectious irritablebowel syndrome (IBS), and vice versa, as IBS patients haveincreased susceptibility to develop infectious gastroenteritis.Various viral (e.g., norovirus), microbial (e.g., Campylobacterjejuni, Clostridium, Mycobacterium), and parasitic agents(e.g., Giardia, helminthes) are known to be involved in thedevelopment of chronic inflammatory bowel diseases. Yet, themechanisms of action are not well known and there is noavailable cure. Additionally, nutritional elements, such as n-3polyunsaturated fatty acids, antioxidants, probiotics, and pre-biotics directly and indirectly modulate GI immunity. Diets

high in fat change the populations of innate microbiome indigestive tract and alter signaling to the brain and satiety,leading to obesity and inflammation.

H. pylori CagA and IL-1𝛽. Gastric cancer is the 3rd cause ofcancer mortality globally and infection by Helicobacter (H.pylori) infecting about 50% globally. It is a main risk factorfor gastric cancer by the activity of virulence factor, CagA.H. pylori/CagA causes chronic inflammation and triggersgastric lesions leading to cancer. IL-1𝛽 is linked with tumorprogression including gastric cancer. Inflammatory cytokinesand IL-1𝛽 are associated with H. pylori infection but linkbetween gastric cancer and IL-1𝛽 was reported before. H.Arevalo-Romero et al. report a link between CagA andIL-1𝛽 which triggers the instigation of the epithelia tomesenchymal cells by 𝛽-catenin nuclear translocation. Inaddition, it increases the expression of Snail1 and ZEB1 anddownregulates morphological changes of nontransformedepithelial cells,MCF-10A, into acini formation. CagA by itselfinduced MMP9 activity and cell invasion. Authors presentdata to support the fact that IL-1𝛽 and CagA trigger the 𝛽-catenin pathway, leading to progression of aggressive tumors.

H. pylori andMetabolic Syndrome.H. pylori infects about 50%of global population with increased risk of atherosclerosis.Similarly, patients with metabolic syndrome are at increasedrisk of atherosclerosis. To assess the effects of H. pyloriinfection on serum lipids, body mass index, and metabolicsyndrome in old Chinese people, in a clinical trial W. Yangand C. Xuan studied association of H. pylori and metabolic

Hindawi Publishing CorporationGastroenterology Research and PracticeVolume 2016, Article ID 6516708, 3 pageshttp://dx.doi.org/10.1155/2016/6516708

2 Gastroenterology Research and Practice

syndrome in those who had gastroscopy exam. H. Pylori (+)patients had higher BMI, fasting glucose concentration, anda higher incidence of metabolic syndrome. In addition, theydemonstrated that H. pylori infection, total cholesterol, anddiabetes mellitus are significantly associated with the risk ofmetabolic syndrome.

H. pylori and Nutrition. Diet and nutrition influence H.pylori-associated disease result. In this review K. P. Haley andJ. A. Gaddy discuss H. pylori ability to modify the host-immune response and to compete for the essential micronu-trients. For instance, iron as well as zinc has great effect onhost defense and pathogens interaction.H. pylori has evolvedto deal with zinc stressor against microorganisms growth inhuman stomach by encoding multiple proteins involved inzinc efflux through its genome. In addition, H. pylori canchange gastric flora to promote carcinogenesis, by increasingnitrosylating bacterial strains which convert nitrogen com-pounds in gastric fluid to carcinogens such asN-nitrosaminesor nitric oxide. Authors discuss several aspects includingthose nutritional factors which can protect against H. pyloriinfection.

Metagenomic and Gut Microbial Diversity. Gut microbiomemaintains nutrients metabolism and homeostasis of immunesystem. Metagenomics have provided the tools to explorerelation betweenmicrobiome, dysbiosis, and state of diseases.A reliable methodology to profile gastrointestinal micro-biome can help to reveal pathogenesis of several chronicinflammatory and infectious diseases and further to developnew preventive and therapeutic modalities. F. Benoit et al.apply profiling technology to study fecal samples from mice,cat, and a human subject. They discuss interindividual vari-ations between these samples. Authors suggest the techniquemay be useful for clinical diagnostics in diet follow-up andtreatments when appropriate controls are applied.

Prealbumin/CRP Score for PredictingMetastasis. Patients withgastric cancer have a poor prognosis with variation in theirduration of survival. An appropriate prognostic technologymay improve clinical care in patients. Z. Ghoreishi et al.assessed nutritional status and systemic inflammatory res-ponse of the patients before chemotherapy and present a newscore system to predict metastasis. They compared prealbu-min/CRP based prognostic score to compare with Glasgowprognostic score for predicting metastasis and nutritionalstatus in patients. Authors discuss in detail statistical differ-ence levels of prealbumin and CRP between patients withmetastatic and nonmetastatic gastric cancer compared toother current methods to predict survival in this population.Future studies with large sample sizewill reveal the usefulnessof this prognostic scoring system.

Fish Oil, Microbiota, and Ethanol Induced Hepatic Injury.Chronic consumption of ethanol may lead to oxidative stress,hepatic injury, alcoholic liver disease, and eventually cirrho-sis. S.-C. Yang et al. investigated fish oil protective effects onhepatic structure in ethanol-fed rats based on the intestinalpermeability and microbiota compared to olive oil. Ethanol

induces dysbiosis, to disrupt intestinal barrier and increasepermeability and endotoxemia. As was expected, liver enzy-mes activities, hepatic inflammatory cytokines, and plasmaendotoxin levels were significantly upregulated in ethanolgroup with increased intestinal permeability and decreasednumbers of fecal bifidobacteria (𝑝 < 0.05). However, thesepathological effects were significantly ameliorated in thosethat received fish oil. The fecal E. coli lowered, but fecalbifidobacteria numbers were significantly increased in fish oilgroups compared to olive oil. Authors conclude that dietaryfish oil in ethanol consumption may normalize increasedintestinal permeability and fecal microbial composition andreduce endotoxins and inflammatory cytokines and liverinjury.

Prebiotic Formula Improves GI Bacterial Flora. Y.-L. Chen andcoworkers screened healthy toddlers (18 months to 3 years)to investigate the impact of prebiotic containing formula(inulin, fructooligosaccharides, and galactooligosaccharides)on their GI microflora given 3 times a day for 6 weeks. Thecontrol formula with no prebiotics was delivered one weekbefore and after the treatment period. Fecal samples wereexamined at different time points to measure the anaerobicbacteria, Bifidobacterium spp., and Clostridium perfringens.In addition, organic acids such as lactate, acetate, propionate,and butyrate were measured in the feces using high-perfor-mance liquid chromatography. The population of probioticBifidobacterium spp. significantly increased, while the totalanaerobic bacteria and harmful C. perfringens were suppres-sed after 6-week administration period. Compared to that inthe control period, the ratio of Bifidobacterium spp. to thetotal anaerobic bacteria significantly increased, and the ratioof C. perfringens to total anaerobes was significantly reduced.Furthermore, the levels of organic acids in the fecal samplessignificantly increased after consumption of prebiotic form-ula. Authors concluded that supplementation with the 3-pre-biotic toddler formula may be beneficial for children’s guthealth.

Xylooligosaccharides and Microbiota. Probiotics are known tofeed on prebiotics to support their growth and gut health. In apilot trial S.-H. Lin et al. investigated the effects of short chainfatty acid (prebiotic) xylooligosaccharides and enriched riceporridge (combination cocktail) consumption additives intodaily diet on the intestinal tract of human subjects. Twentyhealthy subjects participated in a 6-week trial, in which halfof subjects received the cocktail while the other 1/2 receivedplacebo (rice porridge alone). Fecal samples at differenttime points were examined to study microflora. Investigatorsreveal daily consumption of the prebiotic cocktail to inducesignificant increases in fecal microbial counts in Lactobacillusspp. and Bifidobacterium spp., yet to decrease undesiredClostridium perfringens compared to placebo rice porridge.However, some changes occurring in the counts of coliformsin both groups may relate to possible favored effects by riceporridge. Authors conclude that improvement in intestinalmicrobiota balance supports the possible addition of prebi-otic plus rice porridge into daily diet.

Gastroenterology Research and Practice 3

Tea and Clostridium difficile Infection.The incidence of C. diffinfection and its mortality rate are on the rise in those sus-ceptible. The fecal transplant has shown some benefit in thepatients. Tea and its polyphenols are known best for severalbeneficial actions including antioxidant, anti-inflammatory,and antimicrobial effects. Contrary to beneficial reports ontea M. O. Evans II et al. reason that the antimicrobial effectof tea on gut may act similarly to undesired antibiotics insuspected individuals prone to altered gutmicrobiota to favorinfection and C. diff recurrence. In a retrospective cross-sectional dietary survey investigators recruit subjects whohad been diagnosed with C. diff infection episodes in past.From 64 enrolled patients to list their daily diet 19 had experi-enced recurrent episodes. A statistically significant number ofpatients with recurrence compared to nonrecurrence patientshad used antibiotics (𝑝 = 0.003) or recorded tea (𝑝 = 0.002),coffee (𝑝 = 0.013), and eggs (𝑝 = 0.013), on 24-hour foodrecall. Authors conclude a possible link between tea drinkingand C. diff recurrence to negatively affect the gut microbiotato support growth of C. diff. Future clinical trials are requiredto confirmwhether tea supports the growth ofC. diff in theserecurrent patients.

Matrix Metalloproteinases, Inhibitors, and IBD. While theetiology of chronic inflammatory bowel disease is still underdebate a series of inflammatory mediators are known toignite the complication. Metalloproteinase (MMPs) prote-olytic zinc-dependent enzymes are involved in remodelingand degradation of extracellular matrix and wound healing,as well as rheumatoid arthritis, atherosclerosis, and tumormetastasis. K. Jakubowska et al. report expression of MMPsto be distinctive in Crohn’s disease compared to ulcerativecolitis.The overexpression of MMPs and significantly weakerexpression of the inhibitors may determine the developmentof IBD. Ulcerative colitis patients in particular demonstratea significant correlation between increased MMPs expres-sion and histopathological markers with disease progression.Authors suggest MMPs (2, 7, and 9) as potential therapeutictarget and their inhibitors to reduce ulcerative colitis progres-sion.

Mucosal Barrier and Crohn’s Disease. The genetics, immunity,and environment factors are tightly regulating the progres-sion of Crohn’s disease in patients. Gut microbiota protectsintestinal mucosa against inflammations. As dysfunction ofintestinal mucosal barriers due to immune disorders andinfections initiate Crohn’s development, additional studiesare required to explain exact protective action of intestinalmucosal barrier’s in Crohn’s disease. K. Wang et al. recapit-ulate recent findings regarding the correlations between thedisorders of intestinal mucosal defenses including mechan-ical, chemical, immune, and biological barriers and Crohn’sdisease.

Syndecan-1 and Intestinal Epithelial Inflammation. Syndecan-1 (SDC1) is heparan sulfate proteoglycans (HSPGs) mainlyexpressed on the surface of epithelial cells. SDC1 is known toinhibit migration of neutrophils by downregulating chemo-kines and cytokines expression. Y. Zhang et al. examine the

role of SDC1 in intestinal inflammatory responses using atransfected intestinal epithelial cell model. Authors concludethat suppressing SDC1 release from epithelial cells ame-liorates severity of intestinal inflammation by inactivatingNF-𝜅B pathway and downregulating TNF𝛼 expression andsuggesting the use of SDC1 as a possible targeted therapy.

Rifaximin andMutaflor Synergy against Colitis. A. Dembinskiet al. investigated the effect of antibacterial agent, rifaximin,and/orMutaflor, a nonpathogenic bacteria strain (EscherichiacoliNissle 1917), administration on the healing of acetic acid-induced colitis in rats. The authors found that rifaximin andMutaflor had synergic anti-inflammatory and therapeuticeffects in colitis. This finding implies the interaction betweenantibiotics coadministered with probiotics as a possible alter-native choice in the treatment of colitis.

Effectiveness and Safety of Entecavir versus Lamivudine. Thisis a systematic review andmeta-analysis of 1254 patients withhepatitis B viral (HBV) infections-associated acute-on-chro-nic liver failure. J. Yang et al. focus on 2 commonly usedantiviral treatments, entecavir and lamivudine, for effective-ness and safety in HBV patients. Authors report entecavir tobe significantly more effective and with higher survival ratethan lamivudine in patients treated after 1 year. As for thesafety, both drugs (entecavir and lamivudine) were found tobe equally safe and well tolerated in patients. Further meta-analysis research needs to be conducted on adverse effects ofentecavir in prolonged treatments.

Molecular Diversity and Sapovirus Infection. Sapovirus, acalicivirus, is an important pathogen involved in nonbacterialacute gastroenteritis. This study investigated the moleculardiversity of Sapovirus in outpatients with acute gastroenteritisfrom the city of Nanjing in China from 2011 to 2013. H.Zhang et al. used real-time PCR with specific primers andprobes targeted at conserved regions of the RNA polymeraseto human Sapovirus. The results showed that, compared tothe reference strains, different amino acid substitutions werefound in the Nanjing strain. Whether these substitutions areinvolved in the antigenic changes or the virus fitness to hostsrequires further investigation. However, this study providessome cues in the treatment of Sapovirus-induced enteritis inthe future.

Helieh S. OzSung-Ling Yeh

Manuela G. Neuman

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Editorial Gastrointestinal Inflammation and Repair: Role ...downloads.hindawi.com/journals/grp/2016/6516708.pdf · H. pylori CagA and IL- . Gastric cancer is the rd cause of cancer