Search

Eduardo Sepúlveda,1,2 Rui Poínhos,2,3 Miguel Constante,4,5 José Pais-Ribeiro,1,2 Paula Freitas,6–8 Davide Carvalho6–8 1Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal; 2Associação de Prevenção e Apoio à Diabetes, Porto, Portugal; 3Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal; 4Institute of Psychiatry, King's College London, London, UK; 5Department of Psychiatry, Hospital Beatriz Ângelo, Loures, Portugal; 6Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal; 7Faculty of Medicine, University of Porto, Porto, Portugal; 8Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Background: The aim of this study was to assess the relationship between health-related quality of life (HRQoL) and the presence or absence of hypertension and diabetes-related chronic complications in type 2 diabetes, and also the association between HRQoL and the number of chronic complications. Methods: One hundred patients with type 2 diabetes were interviewed. HRQoL was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). Results: The mean age of the study population was 62.7±8.7 years; 54.0% were male, and 51.0% were receiving only oral hypoglycemic agents. Chronic complications were related to worse HRQoL in different dimensions: peripheral neuropathy and cardiovascular disease (all, except bodily pain), retinopathy (physical functioning, general health, vitality, and mental health), peripheral arterial disease (physical functioning, role-physical, and general health), and nephropathy (general health and vitality). Hypertension was related to worse general health and vitality. An increased number of chronic complications was associated with worse HRQoL in all dimensions of Short-Form 36 except for the bodily pain dimension. Conclusion: The presence and increased number of diabetes-related chronic complications, and the presence of hypertension were related to worse age-adjusted HRQoL. Peripheral neuropathy and cardiovascular disease were more strongly related to age-adjusted HRQoL. Keywords: retinopathy, nephropathy, peripheral neuropathy, cardiovascular disease, peripheral arterial disease

Eduardo Sepúlveda,1,2 Rui Poínhos,2,3 Miguel Constante,4,5 José Pais-Ribeiro,1,2 Paula Freitas,6,7 Davide Carvalho6,71Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal; 2Associação de Prevenção e Apoio à Diabetes, Porto, Portugal; 3Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal; 4Institute of Psychiatry, King’s College London, London, UK; 5Department of Psychiatry, Hospital Beatriz Ângelo, Loures, Portugal; 6Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal; 7Faculty of Medicine, University of Porto, Porto, PortugalBackground: Diabetes mellitus is a chronic metabolic disease, the prevalence of which has registered a considerable increase, mainly in adults and elderly. The purpose of this study was to assess the relationship between health-related quality of life in patients with diabetes and sex, body mass index, type of diabetes and treatment regimens (type 1 diabetes: intensive versus conventional treatment; type 2 diabetes: insulin use versus non-insulin use), and duration of diabetes.Methods: One hundred and twenty-four patients with diabetes were interviewed. Health-related quality of life was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), and related to demographic and clinical variables. Independent samples t-tests and One-Way Analysis of Variance were used to compare means of independent samples. The degree of association between pairs of variables was measured by Pearson’s (r) or Spearman’s (rs) correlation coefficients.Results: The mean age of the study population was 55.7±16.4 years; 54.8% were male, and 77.4% had type 2 diabetes. Females reported worse quality of life than males in all dimensions of the Short-Form 36, except for role-physical and bodily pain. Obese patients had worse physical functioning than normal weight and overweight patients, and worse vitality than their normal weight counterparts. Type 2 diabetic patients taking insulin had lower physical functioning and vitality than those without insulin therapy. Longer duration of diabetes was associated with lower physical functioning, role-physical, general health, vitality, role-emotional, and mental health.Conclusion: Being female, obese, having type 2 diabetes and taking insulin, and having a longer disease duration are characteristics associated with worse age-adjusted quality of life in patients with diabetes.Keywords: clinical variables, demographic variables, diabetes mellitus, health-related quality of life

Copyright of ESPOCH Congresses: The Ecuadorian Journal of S.T.E.A.M. is the property of Knowledge E DMCC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background & Aims: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4 + T cells in CeD., Methods: Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4 + T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants., Results: Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4 + T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4 + T-cell proliferation and activation., Conclusions: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4 + T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Tryptophan is an essential amino acid transformed by host and gut microbial enzymes into metabolites that regulate mucosal homeostasis through aryl hydrocarbon receptor (AhR) activation. Alteration of tryptophan metabolism has been associated with chronic inflammation; however, whether tryptophan supplementation affects the metabolite repertoire and AhR activation under physiological conditions in humans is unknown. We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy volunteers. Subjects on a low tryptophan background diet were randomly assigned to a 3-wk l-tryptophan supplementation (3 g/day) or placebo, and after a 2-wk washout switched to opposite interventions. We assessed gastrointestinal and psychological symptoms by validated questionnaires, AhR activation by cell reporter assay, tryptophan metabolites by liquid chromatography and high-resolution mass spectrometry, cytokine production in isolated monocytes by ELISA, and microbiota profile by 16S rRNA Illumina technique. Oral tryptophan supplementation was well tolerated, with no changes in gastrointestinal or psychological scores. Compared with placebo, tryptophan increased AhR activation capacity by duodenal contents, but not by feces. This was paralleled by higher urinary and plasma kynurenine metabolites and indoles. Tryptophan had a modest impact on fecal microbiome profiles and no significant effect on cytokine production. At the doses used in this study, oral tryptophan supplementation in humans induces microbial indole and host kynurenine metabolic pathways in the small intestine, known to be immunomodulatory. The results should prompt tryptophan intervention strategies in inflammatory conditions of the small intestine where the AhR pathway is impaired. NEW & NOTEWORTHY We demonstrate that in healthy subjects, orally administered tryptophan activates microbial indole and host kynurenine pathways in the small intestine, the primary metabolic site for dietary components, and the richest source of immune cells along the gut. This study provides novel insights in how to optimally activate immunomodulatory AhR pathways and indole metabolism in the small intestine, serving as basis for future therapeutic trials using l-tryptophan supplementation in chronic inflammatory conditions affecting the small intestine.

Background: Mesh repair in incarcerated or strangulated groin hernia is controversial, especially when bowel resection is required. We aimed to perform a meta-analysis comparing mesh and non-mesh repair in patients undergoing emergency groin hernia repair., Methods: We performed a literature search of databases to identify studies comparing mesh and primary suture repair of patients with incarcerated or strangulated inguinal or femoral hernias who underwent emergency surgery. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I 2 statistics., Results: 1095 studies were screened and 101 were thoroughly reviewed. Twenty observational studies and four randomized controlled trials comprising 12,402 patients were included. We found that mesh-based repair had reduced recurrence (OR 0.36; 95% CI 0.19, 0.67; P = 0.001; I 2  = 35%), length of hospital stay (OR - 1.02; 95% CI - 1.87, - 0.17; P = 0.02; I 2  = 94%) and operative time (OR - 9.21; 95% CI - 16.82, - 1.61; P = 0.02; I 2  = 95%) without increasing surgical site infection, mortality or postoperative complications such as seroma, chronic, ileus or urinary retention. In the subgroup analysis of patients that underwent bowel resection, we found that mesh repair was associated with an increased risk of surgical site infection (OR 1.74; 95% CI 1.04, 2.91; P = 0.04; I 2  = 9%)., Conclusions: Mesh repair for incarcerated and strangulated groin hernias reduces recurrence without an increase in postoperative complications and should be considered in clean cases. However, in the setting of bowel resection, mesh repair might increase the incidence of surgical site infection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Obesity is associated with an increased risk of ventral hernia development and recurrence rates after ventral hernia repair (VHR). The metabolic derangements caused by obesity can also lead to many postoperative complications. Therefore, it is a common practice to attempt weight loss before VHR. However, there is still no consensus on optimal preoperative management for obese patients with a ventral hernia. This study aims to perform a meta-analysis to evaluate the effect of preoperative weight optimization on VHR outcomes., Methods: We performed a literature search of PubMed, Scopus, and Cochrane Library databases to identify studies comparing obese patients who underwent surgical or non-surgical weight loss interventions before undergoing hernia repair surgery to obese patients who underwent hernia repair surgery without prehabilitation. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I 2 statistics., Results: One thousand six hundred nine studies were screened and 13 were thoroughly reviewed. Five studies comprising 465 patients undergoing hernia repair surgery were included. No differences in hernia recurrence [odds ratio (OR) 0.66; 95% CI 0.23-1.89; P =0.44; I 2 =20%], seroma (OR 0.70; 95% CI 0.25-1.95; P =0.50; I 2 =5%), hematoma (OR 2.00; 95% CI 0.5-7.94; P =0.45; I 2 =0%), surgical site infection (OR 1.96; 95% CI 0.52-7.40; P =0.32; I 2 =0%), and overall complication (OR 0.80; 95% CI 0.37-1.74; P =0.58; I 2 =40%) rates were noted when comparing patients who underwent a preoperative weight loss intervention (prehabilitation or bariatric surgery) versus those who did not. In the subgroup analysis of patients who underwent bariatric surgery, we found no difference in hernia recurrence (OR 0.64; 95% CI 0.12-3.33; P = 0.59; I 2 =41%) or overall complications (OR 1.14; 95% CI 0.36-3.64; P =0.82; I 2 =64%). In the subgroup analysis of patients who lost weight versus patients who did not, there was no significant difference in overall complication rates (OR 0.86; 95% CI 0.34-2.21; P =0.76; I 2 =55%)., Conclusions: We found similar hernia recurrence, seroma, hematoma, and surgical site infection rates in patients who underwent preoperative optimization. These findings underline the need for prospective studies to define the optimal role of preoperative optimization and weight loss in obese patients undergoing ventral hernia repair., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn's disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice ( Nod2 -/- ; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2 -/- mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.

Background & Aims: Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD primarily affects the small intestine. Thus, we characterized CeD microbiota along the duodenum and in feces and verified functional impact in gnotobiotic mice., Methods: We used 16S rRNA gene sequencing (Illumina) and predicted gene function (PICRUSt2) in duodenal biopsies (D1, D2 and D3), aspirates, and stool from patients with active CeD and controls. CeD alleles were determined in consented participants. A subset of duodenal samples stratified according to similar CeD risk genotypes (controls DQ2 -/- or DQ2 +/- and CeD DQ2 +/- ) were used for further analysis and to colonize germ-free mice for gluten metabolism studies., Results: Microbiota composition and predicted function in CeD was largely determined by intestinal location. In the duodenum, but not stool, there was higher abundance of Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3) in CeD vs controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota., Conclusions: Our results showed luminal and mucosal microbial niches along the gut in CeD. We identified novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD but not in controls carrying DQ2, suggesting an association with active duodenal inflammation. Sampling site should be considered a confounding factor in microbiome studies in CeD., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout ( GCN2 -/- ) mice displayed resistance to anemia compared with wild-type ( GCN2 +/+ ) mice. GCN2 -/- liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2 -/- cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling.

Background: Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide. Methods: Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery-Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide. Results: Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis., Competing Interests: For the EUDOR-A study, the participating centres (MS, MI, PZ, CG, MA, EB-G, AB, DC, PC, GD, JE, RG, CJ, MH, MC, PMR, PS, and MW) received funding by EMOTRA AB, Sweden to perform the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carli, Hadlaczky, Petros, Iosue, Zeppegno, Gramaglia, Amore, Baca-Garcia, Batra, Cosman, Courtet, Di Sciascio, Ekstrand, Galfalvy, Gusmão, Jesus, Heitor, Constante, Rad, Saiz, Wojnar and Sarchiapone.)

Background & Aims: Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown., Methods: We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs)., Results: Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC-colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice., Conclusions: We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms., Methods: Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification., Key Results: Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels., Conclusions & Inferences: Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria., (© 2020 John Wiley & Sons Ltd.)

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand production by the gut microbiota could influence gluten immunopathology in nonobese diabetic (NOD) mice expressing DQ8, a celiac disease susceptibility gene. NOD/DQ8 mice, exposed or not exposed to gluten, were subjected to three interventions directed at enhancing AhR pathway activation. These included a high-tryptophan diet, gavage with Lactobacillus reuteri that produces AhR ligands or treatment with an AhR agonist. We investigated intestinal permeability, gut microbiota composition determined by 16 S rRNA gene sequencing, AhR pathway activation in intestinal contents, and small intestinal pathology and inflammatory markers. In NOD/DQ8 mice, a high-tryptophan diet modulated gut microbiota composition and enhanced AhR ligand production. AhR pathway activation by an enriched tryptophan diet, treatment with the AhR ligand producer L. reuteri , or pharmacological stimulation using 6-formylindolo (3,2-b) carbazole (Ficz) decreased immunopathology in NOD/DQ8 mice exposed to gluten. We then determined AhR ligand production by the fecal microbiota and AhR activation in patients with active celiac disease compared to nonceliac control individuals. Patients with active celiac disease demonstrated reduced AhR ligand production and lower intestinal AhR pathway activation. These results highlight gut microbiota-dependent modulation of the AhR pathway in celiac disease and suggest a new therapeutic strategy for treating this disorder., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Syncope caused by carotid sinus syndrome due to head and neck cancer is rare. We report a case of recurrent syncope as a result of extreme bradycardia requiring pacemaker implantation. The patient began chemotherapy and radiation therapy to treat the underlying cause. When diagnosed early, a positive outcome is expected in these situations., Learning Points: The differential diagnosis of transient loss of consciousness is frequently evident at clinical examination but may prove to be a challenge.The invasion and direct compression of the carotid sinus is a rare cause of carotid sinus syndrome and presents clinically as syncope., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Emphysematous gastritis is a rare disease characterised by air in the wall of the stomach due to gas-forming microorganisms. This is a highly lethal entity for which only prompt diagnosis and treatment can avoid mortality. Different factors have been described that disrupt the integrity of the mucosa such as corrosive ingestion, alcohol abuse, recent abdominal surgery or cancer. We report a case of emphysematous gastritis in a 92-year-old woman who presented to the emergency department with abdominal pain, nausea and vomiting. Inflammatory markers were elevated and abdominal X-rays showed intramural gastric air, confirmed by CT scan. The patient received intravenous fluids, nutritional support and broad-spectrum antibiotic with resolution of gastric wall emphysema. However, the diagnosis of poorly cohesive gastric adenocarcinoma was made and the patient was referred to palliative care. This case highlights the importance of prompt recognition of this lethal entity that represents a rare and aggressive presentation of gastric cancer., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A low fermentable carbohydrate (FODMAP) diet is used in quiescent inflammatory bowel disease when irritable bowel syndrome-like symptoms occur. There is concern that the diet could exacerbate inflammation by modifying microbiota and short-chain fatty acid (SCFA) production. We examined the effect of altering dietary FODMAP content on inflammation in preclinical inflammatory models., Methods: C57BL/6 mice were given 3% dextran sodium sulfate (DSS) in drinking water for 5 days and recovered for 3 weeks (postinflammatory, n = 12), or 5 days (positive-control, n = 12). Following recovery, DSS-treated or control mice (negative-control, n = 12) were randomized to 2-week low- (0.51 g/100 g total FODMAP) or high-FODMAP (4.10 g) diets. Diets mimicked human consumption containing fructose, sorbitol, galacto-oligosaccharide, and fructan. Colons were assessed for myeloperoxidase (MPO) activity and histological damage. Supernatants were generated for perforated patch-clamp recordings and cytokine measurement. Cecum contents were analyzed for microbiota, SCFA, and branched-chain fatty acids (BCFA). Data were analyzed by two-way ANOVA with Bonferroni., Key Results: Inflammatory markers were higher in the positive-control compared with negative-control and postinflammatory groups, but no differences occurred between the two diets within each treatment (MPO P > .99, histological scores P > .99, cytokines P > .05), or the perforated patch-clamp recordings (P > .05). Microbiota clustered mainly based on DSS exposure. No difference in SCFA content occurred. Higher total BCFA occurred with the low-FODMAP diet in positive-control (P < .01) and postinflammatory groups (P < .01)., Conclusions and Inferences: In this preclinical study, reducing dietary FODMAPs did not exacerbate nor mitigate inflammation. Microbiota profile changes were largely driven by inflammation rather than diet. Low FODMAP intake caused a shift toward proteolytic fermentation following inflammation., (© 2019 John Wiley & Sons Ltd.)

Anemia is frequently encountered in patients with inflammatory bowel disease (IBD), decreasing the quality of life and significantly worsening the prognosis of the disease. The pathogenesis of anemia in IBD is multifactorial and results mainly from intestinal blood loss in inflamed mucosa and impaired dietary iron absorption. Multiple studies have proposed the use of the polyphenolic compound curcumin to counteract IBD pathogenesis since it has significant preventive and therapeutic properties as an anti-inflammatory agent and very low toxicity, even at high dosages. However, curcumin has been shown to possess properties consistent with those of an iron-chelator, such as the ability to modulate proteins of iron metabolism and decrease spleen and liver iron content. Thus, this property may further contribute to the development and severity of anemia of inflammation and iron deficiency in IBD. Herein, we evaluate the effects of curcumin on systemic iron balance in the dextran sodium sulfate (DSS) model of colitis in C57Bl/6 and BALB/c mouse strains that were fed an iron-sufficient diet. In these conditions, curcumin supplementation caused mild anemia, lowered iron stores, worsened colitis and significantly decreased overall survival, independent of the mouse strain. These findings suggest that curcumin usage as an anti-inflammatory supplement should be accompanied by monitoring of erythroid parameters to avoid exacerbation of iron deficiency anemia in IBD., Competing Interests: The authors have declared that no competing interests exist.

Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the underlying mechanisms are incompletely understood. Here we show that duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten substrates that correlates with increased Proteobacteria abundance, including Pseudomonas. Using Pseudomonas aeruginosa producing elastase as a model, we show gluten-independent, PAR-2 mediated upregulation of inflammatory pathways in C57BL/6 mice without villus blunting. In mice expressing CeD risk genes, P. aeruginosa elastase synergizes with gluten to induce more severe inflammation that is associated with moderate villus blunting. These results demonstrate that proteases expressed by opportunistic pathogens impact host immune responses that are relevant to the development of food sensitivities, independently of the trigger antigen.

Patients with systemic sclerosis (SSc) display altered intestinal microbiota. However, the influence of intestinal dysbiosis on the development of experimental SSc remains unknown. Topoisomerase I peptide-loaded dendritic cell immunization induces SSc-like disease, with progressive skin and lung fibrosis. Breeders were given streptomycin and pups continued to receive antibiotic (ATB) until endpoint (lifelongATB). Alternately, ATB was withdrawn (earlyATB) or initiated (adultATB) during adulthood. Topoisomerase I peptide-loaded dendritic cell (no ATB) immunization induced pronounced skin fibrosis, with increased matrix (Col1a1), profibrotic (Il13, Tweakr), and vascular function (Serpine1) gene expression. Remarkably, earlyATB exposure was sufficient to augment skin Col5a1 and Il13 expression, and inflammatory cell infiltration, which included IL-13 + cells, mononuclear phagocytes, and mast cells. Moreover, skin pathology exacerbation was also observed in lifelongATB and adultATB groups. Oral streptomycin administration induced intestinal dysbiosis, with exposure limited to early life (earlyATB) being sufficient to cause long-term modification of the microbiota and a shift toward increased Bacteroidetes/Firmicutes ratio. Finally, aggravated lung fibrosis and dysregulated pulmonary T-cell responses were observed in earlyATB and lifelongATB but not adultATB-exposed mice. Collectively, intestinal microbiota manipulation with streptomycin exacerbated pathology in two distinct sites, skin and lungs, with early life being a critical window to affect the course of SSc-like disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD), where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria , particularly Enterobacteriaceae . These changes were similar to shifts seen in dextran sodium sulfate (DSS)-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC) mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis. Thus, luminal heme levels may further exacerbate colitis through the modulation of the gut microbiota and its metagenomic functional composition. Our data may have implications in the development of novel targets for therapeutic approaches aimed at lowering gastrointestinal heme levels through heme chelation or degradation using probiotics and nutritional interventions.