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Abstract Background Bast fibres from the phloem tissues of flax are scientifically interesting and economically useful due in part to a dynamic system of secondary cell wall deposition. To better understand the molecular mechanisms underlying the process of cell wall development in flax, we extracted proteins from individually dissected phloem fibres (i.e. individual cells) at an early stage of secondary cell wall development, and compared these extracts to protein extracts from surrounding, non-fibre cells of the cortex, using fluorescent (DiGE) labels and 2D-gel electrophoresis, with identities assigned to some proteins by mass spectrometry. Results The abundance of many proteins in fibres was notably different from the surrounding non-fibre cells of the cortex, with approximately 13% of the 1,850 detectable spots being significantly (> 1.5 fold, p ≤ 0.05) enriched in fibres. Following mass spectrometry, we assigned identity to 114 spots, of which 51 were significantly enriched in fibres. We observed that a K+ channel subunit, annexins, porins, secretory pathway components, β-amylase, β-galactosidase and pectin and galactan biosynthetic enzymes were among the most highly enriched proteins detected in developing flax fibres, with many of these proteins showing electrophoretic patterns consistent with post-translational modifications. Conclusion The fibre-enriched proteins we identified are consistent with the dynamic process of secondary wall deposition previously suggested by histological and biochemical analyses, and particularly the importance of galactans and the secretory pathway in this process. The apparent abundance of β-amylase suggests that starch may be an unappreciated source of materials for cell wall biogenesis in flax bast fibres. Furthermore, our observations confirm previous reports that correlate accumulation proteins such as annexins, and specific heat shock proteins with secondary cell wall deposition.

Introduction: Fecal microbial transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD)., Methods: This double-blind, placebo-controlled trial was conducted in three Canadian academic centers; randomized patients with mild to moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly fecal capsules for 7 weeks. Primary endpoint was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments., Results: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One participant in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, participants who achieved clinical response became more similar to their donors in stool microbial composition., Discussion: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, biologic or small molecule therapies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

A range of issues related to sustainability in the agrifood industry have spurred interest in mass production of insects as human food and animal feed alternatives. This rapidly evolving sector addresses several challenges, including the management of food waste or agrifood by-products and the production of alternative animal proteins demonstrating low environmental impacts that improve sector circularity. The mass production of insects on agrifood processing wastes or by-products represents an opportunity to address these challenges. While the production of insects offers prospects for sustainable protein production, a major side stream is the production of frass or larval excrement including uneaten feed and chitin-rich exuviae (derived from multiple larval moults). The production of each tonne of edible insects generates 2 to 4 tonnes of frass with an interesting potential in agriculture versus traditional organic amendments (compost, manure, biochar). This review aims to demonstrate the characteristics of frass, its common harvest and conditioning methods, its optimal application rates for planting crops, the mechanisms by which it can protect plants against biotic and abiotic stresses and demystify the risks and potential associated with its application in agriculture. The characteristics of frass are compared with those of conventional fertilizers or other. This report also compiles the Canadian, US and European regulatory frameworks as a novel plant fertilizer and aims to pave the way for future research necessary for its valorization in plant production., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Louise Hénault-Ethier, Alexis Fortin, Étienne Normandin, Guillaume de La Rochelle Renaud are co-founders, and Noémie Hotte was affiliated with TriCycle, an enterprise that produces and markets mealworm frass and edible insect protein. However, all authors confirm that this scientific paper conducted in collaboration with different academic institutions respected the ethical and academic integrity standards. Other authors declare that they have no conflicts of interest regarding this study., (Copyright © 2023. Published by Elsevier Ltd.)

Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders ( n  = 21) and HOMA-IR non-responders ( n  = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders ( p  = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) ( p  < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.

Background: Following viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain-specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-10 -/- ) model derived from the SvEv mouse, had evidence of increased Mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wild type. MMTV is endemic in several mouse strains as an endogenously encoded Betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut-associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10 -/- model., Results: Viral preparations extracted from IL-10 -/- weanling stomachs revealed augmented MMTV load compared to the SvEv wild type. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4-97.3% identity with the mtv-1 endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTV sag gene cloned from IL-10 -/- spleen encoded the MTV-9 superantigen that preferentially activates T-cell receptor Vβ-12 subsets, which were expanded in the IL-10 -/- versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10 -/- splenocytes with amplified interferon-γ production versus the SvEv wild type. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12-week treatment versus placebo. The combination antiretroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL-10 -/- mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis., Conclusions: This study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis. Video Abstract., (© 2023. The Author(s).)

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) that affect women in their childbearing years. Early pregnancy flare-up negatively impacts obstetrical and perinatal outcomes, but the impact on infants is unclear., Aim: To determine whether active IBD disease activity is associated with adverse post-neonatal outcomes post-partum., Methods: This is a single-center cohort study of women with IBD who underwent serial monitoring of post-neonatal outcomes post-partum. Infant outcomes were collected via self-filled questionnaires, including perinatal outcomes, APGAR scores, infant weights, heights, feeding habits and comorbidities within the first year of life., Results: There was a total of 98 women with IBD and 78 live births throughout the study: 50 women were enrolled during trimester one alone and 49 were included into the current study. Among the 49 analyzed, 32 were in remission and 17 were in relapse during trimester one. Trimester one disease activity was associated with more adverse obstetrical outcomes including emergency C-sections and reduced 1-min APGAR scores. At follow-up, infants born to women with T1-flare had reduced weight-for-age Z scores and length-for-age Z scores up to 6 months of age., Conclusions: Active IBD during trimester one is correlated with adverse post-neonatal outcomes, particularly decreased infant weight and height up to 6 months of age. This suggests disease control in first trimester is essential for optimizing infant growth and post-neonatal outcomes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design., Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD., Design: This is a RCT., Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences., Results: Of 150 screened patients, 101 were randomized to the intervention ( n  = 49) and control ( n  = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p  < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets., Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course., Registration: ClinicalTrials.gov Identifier NCT03831750., Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention., (© The Author(s), 2022.)

Inflammatory bowel diseases (IBD), including Ulcerative Colitis (UC) and Crohn’s disease (CD), are inflammatory conditions of the intestinal tract that affect women in their reproductive years. Pregnancy affects Th1- and Th2-cytokines, but how these changes occur during pregnancy in IBD is unclear. We performed a longitudinal profiling of serum cytokines in a cohort of 11 healthy pregnant women and 76 pregnant women with IBD from the first trimester of pregnancy to the first 12 months post-partum. Participants were monitored for biochemical disease activity (C-reactive protein [CRP] and fecal calprotectin [FCP]) and clinical activities. Maternal cytokines were measured using ELISA. We identified changes in Th1 and Th17 cytokines throughout pregnancy in healthy pregnant women. During pregnancy, maternal serum cytokine expressions were influenced by IBD, disease activity, and medications. Active UC was associated with an elevation in IL-21, whereas active CD was associated with elevated IFN-γ, IL-6, and IL-21. Interestingly, T1 serum cytokine levels of IL-22 (>0.624 pg/mL) and IL-6 (>0.648 pg/mL) were associated with worse IBD disease activity throughout pregnancy in women with UC and CD, respectively. This shows serum cytokines in pregnancy differ by IBD, disease activity, and medications. We show for the first time that T1 IL-22 and IL-6 correlate with IBD disease course throughout pregnancy.

Background and Aims: Inflammatory bowel disease (IBD), inclusive of ulcerative colitis and Crohn's disease, are chronic inflammatory conditions that impact women of childbearing age. It has been previously shown that IBD is associated with altered metabolomic profiles, but whether metabolomic changes also affect pregnant patients with IBD is completely unknown., Methods: This was a prospective cohort study comprised of 48 pregnant women with IBD who were followed throughout preconception and pregnancy. IBD disease activity was measured using biochemical markers C-reactive protein or fecal calprotectin using enzyme-linked immunosorbent assay and clinical disease activity using Harvey-Bradshaw Index or partial Mayo scores. Serum and urine samples were collected from preconception, trimester 1, and trimester 2 and analyzed using nuclear magnetic resonance spectroscopy combined with metabolomics set enrichment analysis., Results: We identified a total of 24 urine metabolites and 17 serum metabolites which were altered by active disease across pregnancy. First trimester (T1) active disease-associated metabolites were enriched in "amino acid metabolism" and "fatty-acid β-oxidation." The leading urine metabolites at T1 were trimethyl-N-oxide (TMAO), succinic acid, and 3-hydroxy-2-methylbutyric acid, and leading serum metabolites were TMAO, glucose, and acetic acid. Multivariate modeling using serum TMAO, glucose, and acetic acid predicts T1 disease activity and correlated with mode of delivery and infant weights at delivery. Moreover, cross-time point modeling using metabolomes predicted future disease flare-up during pregnancy., Conclusion: These results suggest select host metabolites may be able to discriminate and predict disease activity and are correlated with pregnancy outcomes at delivery. This warrants further validation of metabolomics to monitor IBD in pregnancy., (© 2022 The Authors.)

Shotgun metagenomics studies have improved our understanding of microbial population dynamics and have revealed significant contributions of microbes to gut homeostasis. They also allow in silico inference of the metagenome. While they link the microbiome with metabolic abnormalities associated with disease phenotypes, they do not capture microbial gene expression patterns that occur in response to the multitude of stimuli that constantly ambush the gut environment. Metatranscriptomics closes that gap, but its implementation is more expensive and tedious. We assessed the metabolic perturbations associated with gut inflammation using shotgun metagenomics and metatranscriptomics. Shotgun metagenomics detected changes in abundance of bacterial taxa known to be SCFA producers, which favors gut homeostasis. Bacteria in the phylum Firmicutes were found at decreased abundance, while those in phyla Bacteroidetes and Proteobacteria were found at increased abundance. Surprisingly, inferring the coding capacity of the microbiome from shotgun metagenomics data did not result in any statistically significant difference, suggesting functional redundancy in the microbiome or poor resolution of shotgun metagenomics data to profile bacterial pathways, especially when sequencing is not very deep. Obviously, the ability of metatranscriptomics libraries to detect transcripts expressed at basal (or simply low) levels is also dependent on sequencing depth. Nevertheless, metatranscriptomics informed about contrasting roles of bacteria during inflammation. Functions involved in nutrient transport, immune suppression and regulation of tissue damage were dramatically upregulated, perhaps contributed by homeostasis-promoting bacteria. Functions ostensibly increasing bacteria pathogenesis were also found upregulated, perhaps as a consequence of increased abundance of Proteobacteria. Bacterial protein synthesis appeared downregulated. In summary, shotgun metagenomics was useful to profile bacterial population composition and taxa relative abundance, but did not inform about differential gene content associated with inflammation. Metatranscriptomics was more robust for capturing bacterial metabolism in real time. Although both approaches are complementary, it is often not possible to apply them in parallel. We hope our data will help researchers to decide which approach is more appropriate for the study of different aspects of the microbiome., Competing Interests: The 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 Jovel, Nimaga, Jordan, O’Keefe, Patterson, Thiesen, Hotte, Bording-Jorgensen, Subedi, Hamilton, Carpenter, Lauga, Elahi, Madsen, Wong and Mason.)

Bariatric surgery induces significant microbial and metabolomic changes, however, links between microbial and metabolic pathways have not been fully elucidated. The objective of this study was to conduct a comprehensive investigation of the microbial, metabolomic, and inflammatory changes that occur following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A prospective clinical trial was conducted with participants undergoing RYGB, SG, and non-operative controls (CTRL). Clinical parameters, blood samples, and fecal samples were collected pre-intervention and at 3 and 9 months. A multi-omics approach was used to perform integrated microbial-metabolomic analysis to identify functional pathways in which weight loss and metabolic changes occur after surgery. RYGB led to profound microbial changes over time that included reductions in alpha-diversity, increased Proteobacteria and Verrucomicrobiota, decreased Firmicutes, and numerous changes at the genera level. These changes were associated with a reduction in inflammation and significant weight loss. A reduction in Romboutsia genera correlated strongly with weight loss and integrated microbial-metabolomic analysis revealed the importance of Romboutsia . Its obliteration correlated with improved weight loss and insulin resistance, possibly through decreases in glycerophospholipids. In contrast, SG was associated with no changes in alpha-diversity, and only a small number of changes in microbial genera. A cluster of Firmicutes genera including Butyriciccocus, Eubacterium ventriosum , and Monoglobus was decreased, which correlated with decreased weight, insulin resistance, and systemic inflammation. This work represents comprehensive analyses of microbial-metabolomic changes that occur following bariatric surgery and identifies several pathways that are associated with beneficial metabolic effects of surgery.

Roux-en-Y gastric bypass (RYGB)-induced glycemic improvement is associated with increases in glucagon-like-peptide-1 (GLP-1) secreted from ileal L-cells. We analyzed changes in ileal bile acids and ileal microbial composition in diet-induced-obesity rats after RYGB or sham surgery to elucidate the early and late effects on L-cells and glucose homeostasis. In early cohorts, there were no significant changes in L-cell density, GLP-1 or glucose tolerance. In late cohorts, RYGB demonstrated less weight regain, improved glucose tolerance, increased L-cell density, and increased villi height. No difference in the expression of GLP-1 genes was observed. There were lower concentrations of ileal bile acids in the late RYGB cohort. Microbial analysis demonstrated decreased alpha diversity in early RYGB cohorts which normalized in the late group. The early RYGB cohorts had higher abundances of Escherichia-Shigella but lower abundances of Lactobacillus, Adlercreutzia, and Proteus while the late cohorts demonstrated higher abundances of Escherichia-Shigella and lower abundances of Lactobacillus. Shifts in Lactobacillus and Escherichia-Shigella correlated with decreases in multiple conjugated bile acids. In conclusion, RYGB caused a late and substantial increase in L-cell quantity with associated changes in bile acids which correlated to shifts in Escherichia-Shigella and Lactobacillus. This proliferation of L-cells contributed to improved glucose homeostasis., (© 2021. The Author(s).)

Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation., Methods: Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks., Results: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia . The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1β ( p = 0.09), IL-6 ( p = 0.03), and TNF-α ( p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 ( p = 0.07) and TNF-α ( p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring., Conclusions: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.

This study examined associations between dietary intake and gut and systemic inflammation assessed by fecal calprotectin ≤ or > 100 μg/mg (FCP), C-reactive protein ≤ or > 5 mg/L (CRP) and serum cytokine profiles in Crohn's disease (CD) patients in clinical remission. A 3-month observational study was conducted at the University of Calgary in Calgary, Alberta, Canada between 2016 and 2018 in 66 outpatients with CD in clinical remission. FCP was obtained from stool samples at baseline and 3-months and serum CRP and serum cytokines were assessed at 3-months only (n = 41). Dietary intakes were collected using 3-day food records at baseline and 3-months and categorized as: PREDIMED Mediterranean diet scores (pMDS) total and individual components, the dietary inflammatory index (DII), food groups, and common micro- and macro-nutrients. Statistical models were developed to identify relationships between dietary factors and FCP, CRP and cytokine levels. Daily intake of leafy green vegetables was associated with FCP ≤ 100 μg/mg (p < 0.05). Increasing omega 6:3 ratio was associated with CRP ≤ 5 mg/L (p = 0.02). Different cytokines were significantly associated with various dietary variables. Future studies in patients with greater disease activity should be undertaken to explore these relationships.

Background and Aims: Crohn's disease [CD] is associated with alterations in gut microbial composition and function. The present controlled-intervention study investigated the relationship between patterns of dietary intake and baseline gut microbiota in CD patients in remission and examined the effects of a dietary intervention in patients consuming a non-diversified diet [NDD]., Methods: Forty outpatients with quiescent CD were recruited in Calgary, Alberta, Canada. Based on 3-day food records, patients consuming a lower plant-based and higher red and processed meat-based diet were assigned to the NDD group [n = 15] and received a 12-week structured dietary intervention; all other patients were assigned to the diversified diet [DD] control group [n = 25] and received conventional management. Faecal microbiota composition, short chain fatty acids [SCFAs] and calprotectin were measured., Results: At baseline the NDD and DD groups had a different faecal microbial beta-diversity [p = 0.003, permutational multivariate analysis of variance]. The NDD group had lower Faecalibacterium and higher Escherichia/Shigella relative abundances compared to the DD group [3.3 ± 5.4% vs. 8.5 ± 10.6%; 6.9 ± 12.2% vs. 1.6 ± 4.4%; p ≤ 0.03, analysis of covariance]. These two genera showed a strong negative correlation [rs = -0.60, q = 0.0002]. Faecal butyrate showed a positive correlation with Faecalibacterium [rs = 0.52, q = 0.002], and an inhibitory relationship with Escherichia/Shigella abundance [four-parameter sigmoidal model, R = -0.83; rs = -0.44, q = 0.01], respectively. After the 12 weeks of dietary intervention, no difference in microbial beta-diversity between the two groups was observed [p = 0.43]. The NDD group demonstrated an increase in Faecalibacterium [p < 0.05, generalized estimated equation model], and resembled the DD group at the end of the intervention [p = 0.84, t-test with permutation]. We did not find an association of diet with faecal SCFAs or calprotectin., Conclusions: Dietary patterns are associated with specific gut microbial compositions in CD patients in remission. A diet intervention in patients consuming a NDD modifies gut microbial composition to resemble that seen in patients consuming a DD. These results show that diet is important in shaping the microbial dysbiosis signature in CD towards a balanced community., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There is growing interest in studying dietary fiber to stimulate microbiome changes that might prevent or alleviate inflammatory bowel disease (IBD). However, dietary fiber effects have shown varying degrees of efficacy, for reasons that are unclear. This study examined whether the effects of isomaltodextrin on gut microbiota and IBD were dependent on dose or host sex, using an Interleukin (IL)-10 deficient murine colitis model. After 12 weeks, colonic IL-12p70 was depressed in male mice receiving high-dose isomaltodextrin supplementation compared to the control group ( p = 0.04). Male mice receiving high-dose isomaltodextrin exhibited changes in microbial alpha-diversity, including enhanced richness and evenness ( p = 0.01) and limited reduction in the relative abundance of Coprococcus ( q = 0.08), compared to the control group. These microbial compositional changes were negatively associated with IL-12p70 levels in the male group (rs ≤ -0.51, q ≤ 0.08). In contrast, female mice receiving isomaltodextrin displayed a reduction in alpha-diversity and Coprococcus abundance and a high level of IL-12p70, as did the control group. Together, these results indicate that isomaltodextrin altered the gut microbial composition linking specific immune-regulatory cytokine responses, while the interactions among fiber, microbiota and immune response were dose dependent and largely sex specific. The results further indicate that interactions between environmental and host factors can affect microbiome manipulation in the host.

Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.

Intravenous immunoglobulin (IVIg) is used to treat immune-mediated diseases but its mechanism of action is poorly understood. We have reported that co-treatment with IVIg and lipopolysaccharide activates macrophages to produce large amounts of anti-inflammatory IL-10 in vitro. Thus, we asked whether IVIg-treated macrophages or IVIg could reduce intestinal inflammation in mice during dextran sulfate sodium (DSS)-induced colitis by inducing macrophage IL-10 production in vivo. Adoptive transfer of IVIg-treated macrophages reduces intestinal inflammation in mice and collagen accumulation post-DSS. IVIg treatment also reduces DSS-induced intestinal inflammation and its activity is dependent on the Fc portion of the antibody. Ex vivo, IVIg induces IL-10 production and reduces IL-12/23p40 and IL-1β production in colon explant cultures. Co-staining tissues for mRNA, we demonstrate that macrophages are the source of IL-10 in IVIg-treated mice; and using IL-10-GFP reporter mice, we demonstrate that IVIg induces IL-10 production by intestinal macrophages. Finally, IVIg-mediated protection is lost in mice deficient in macrophage IL-10 production (LysMcre +/- IL-10 fl/fl mice). Together, our data demonstrate a novel, in vivo mechanism of action for IVIg. IVIg-treated macrophages or IVIg could be used to treat people with intestinal inflammation and may be particularly useful for people with inflammatory bowel disease, who are refractory to therapy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Aims: For women with inflammatory bowel disease [IBD], it is not very well known how IBD or IBD treatment affects their breast milk components. We aimed to investigate whether breast milk composition differs in healthy control [HC] versus IBD mothers in terms of antibodies, cytokines, and metabolite,s to identify potential impact of IBD breast milk on neonatal immune system., Methods: Breast milk specimens from HC [n = 17] and IBD [n = 31 for Crohn's disease [CD]; and n = 41 for ulcerative colitis [UC]; were collected at 3 and 6 months postpartum [PP3] and [PP6], respectively. Faecal samples were also collected. Cytokines and immunoglobulins [IgA/IgG/IgE] were analysed by multiplex Meso Scale Discovery [MSD] and commercial kits. Moreover, breast milk metabolites were analysed by 1H nuclear magnetic resonance [NMR]., Results: We found that breast milk from IBD mothers showed significantly lower levels of IgA, sugar metabolite [lactose], and 2-aminobutyrate. In contrast, we observed that breast milk from mothers with IBD had increased levels of pro-inflammatory cytokines and higher energy metabolites [lactate and succinate] than milk from healthy mothers. In addition, we noticed that the type of treatment [5-aminosalicylic acid versus biologics] influenced the milk cytokines and metabolites profile., Conclusions: The reduction in immunoprotective components of IBD breast milk such as sIgA and lactose theoretically may modulate the potential protective effects of breastfeeding. On the other hand, presence of higher levels of pro-inflammatory cytokines, lactate, and succinate may predispose the offspring to an inflammatory condition or impact on the gut microbiome. Better understanding of the role of succinate in infants and its potential effects on microbiome or mucosal immunity merits further investigations., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: CD71+ erythroid cells are enriched during pregnancy with immuno suppressive properties. We investigated the frequency and functionality of CD71+ erythroid cells in peripheral blood, cord blood, and placenta of inflammatory bowel disease [IBD] patients versus healthy controls [HCs]. We aimed to determine their role in IBD pathogenesis during pregnancy., Methods: Peripheral blood was collected at preconception, the first, second and third trimesters, and postpartum. Cord blood and placental tissues were collected at the time of birth. Cells from different specimens were subjected to immune-phenotyping and functional assays. CD71+ erythroid cells were purified for quantitative polymerase chain reaction [qPCR] analysis. Using an allogeneic mouse model of pregnancy, the effects of CD71+ erythroid cells depletion on intestinal homeostasis and dysbiosis was studied., Results: IBD patients had lower CD71+ erythroid cells during pregnancy compared with HCs. Placenta and cord blood CD71+ erythroid cells from IBD patients exhibited impaired functionality and expressed lower inhibitory molecules including VISTA, TGF-β, and reactive oxygen species [ROS]. Lower CD71+ erythroid cells were correlated with reduced regulatory T cells and increased immune-activation in IBD patients. Depletion of CD71+ erythroid cells in an allogeneic pregnancy model resulted in upregulation of TLRs, IL-6, and CXCL-1, and enhanced production of TNF-α, in intestinal tissues. In contrast, TGF-β gene expression was reduced. Excessive inflammatory response in the gut [e.g. TNF-α] affects intestinal integrity and CD71+ erythroid cells impact on the gut's bacterial composition., Conclusions: Reduced frequency and/or impaired functionality of CD71+ erythroid cells during pregnancy may predispose IBD patients to a more pro-inflammatory milieu in their gastrointestinal tract, characterised by lower Tregs, higher IL-6, and TNF-α, and dysbiosis.

Background : Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success. Results : Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia . A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT. Conclusions : In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

Background: Individuals with Crohn's disease frequently require ileocecal resection (ICR), and inflammation often recurs in the neoterminal ileum following surgery. Fructooligosaccharide (FOS) is a fermentable prebiotic that stimulates the growth of bifidobacteria and may promote anti-inflammatory activity. The aim of this study was to determine if supplementation of a postICR diet with FOS in a mouse model would be effective in stimulating the growth of bifidobacteria and reducing systemic and local inflammation., Methods: ICR was performed in IL10-/- mice (129S1/SvlmJ) with colitis. Following surgery, nonICR control and ICR mice were fed a chow diet ± 10% FOS for 28 days. Serum, colon, and terminal ileum (TI) were analyzed for cytokine expression by MesoScale discovery platform. DNA extracted from stool was analyzed using 16s rRNA sequencing and qPCR. Expression of occludin and ZO1 was assessed using qPCR. Short-chain fatty acid (SCFA) concentrations were assessed using gas chromatography., Results: ICR led to increased systemic inflammation (P < 0.05) and a significant decline in fecal microbial diversity (P < 0.05). Mice on the FOS diet had a greater reduction in microbial diversity and also had worsened inflammation as evidenced by increased serum IL-6 (P < 0.05) and colonic IFNγ and TNFα (P < 0.05). Expression of occludin and ZO1 were significantly reduced in FOS-supplemented mice. There was a correlation between loss of diversity and the bifidogenic effectiveness of FOS (r = -0.61, P < 0.05)., Conclusions: FOS-supplementation of a postICR diet resulted in a decrease in fecal bacterial diversity, reduction in barrier function, and increased gut inflammation., (© 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes., Methods: In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes., Results: RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT., Conclusions: RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

The advent of next generation sequencing (NGS) has enabled investigations of the gut microbiome with unprecedented resolution and throughput. This has stimulated the development of sophisticated bioinformatics tools to analyze the massive amounts of data generated. Researchers therefore need a clear understanding of the key concepts required for the design, execution and interpretation of NGS experiments on microbiomes. We conducted a literature review and used our own data to determine which approaches work best. The two main approaches for analyzing the microbiome, 16S ribosomal RNA (rRNA) gene amplicons and shotgun metagenomics, are illustrated with analyses of libraries designed to highlight their strengths and weaknesses. Several methods for taxonomic classification of bacterial sequences are discussed. We present simulations to assess the number of sequences that are required to perform reliable appraisals of bacterial community structure. To the extent that fluctuations in the diversity of gut bacterial populations correlate with health and disease, we emphasize various techniques for the analysis of bacterial communities within samples (α-diversity) and between samples (β-diversity). Finally, we demonstrate techniques to infer the metabolic capabilities of a bacteria community from these 16S and shotgun data.

Intravenous Ig is used to treat autoimmune or autoinflammatory disorders, but the mechanism by which it exerts its immunosuppressive activity is not understood completely. To examine the impact of intravenous Ig on macrophages, we compared cytokine production by LPS-activated macrophages in the presence and absence of intravenous Ig. Intravenous Ig treatment induced robust production of IL-10 in response to LPS, relative to LPS stimulation alone, and reduced production of proinflammatory cytokines. This anti-inflammatory, intravenous Ig-induced activation was sustained for 24 h but could only be induced if intravenous Ig were provided within 1 h of LPS stimulation. Intravenous Ig activation led to enhanced and prolonged activation of MAPKs, Erk1/2, p38, and Erk5, and inhibition of each reduced intravenous Ig-induced IL-10 production and suppression of IL-12/23p40. IL-10 production occurred rapidly in response to intravenous Ig + LPS and was sufficient to reduce proinflammatory IL-12/23p40 production in response to LPS. IL-10 induction and reduced IL-12/23p40 production were transcriptionally regulated. IL-10 played a direct role in reducing proinflammatory cytokine production by macrophages treated with intravenous Ig + LPS, as macrophages from mice deficient in the IL-10R β chain or in IL-10 were compromised in their ability to reduce proinflammatory cytokine production. Finally, intraperitoneal injection of intravenous Ig or intravenous Ig + LPS into mice activated macrophages to produce high levels of IL-10 during subsequent or concurrent LPS challenge, respectively. These findings identify IL-10 as a key anti-inflammatory mediator produced by intravenous Ig-treated macrophages and provide insight into a novel mechanism by which intravenous Ig may dampen down inflammatory responses in patients with autoimmune or autoinflammatory diseases., (© Society for Leukocyte Biology.)

Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them.

Background: Prebiotic fibers stimulate the growth and activity of the gut microbiota. Interleukin 10-deficient (IL-10(-/-)) mice develop a colitis that is influenced by the gut microbial composition., Objective: The purpose of this study was to determine the effect of prebiotic fibers on the intestinal microbiota and immune function in IL-10(-/-) mice., Methods: At 4 wk of age, male IL-10(-/-) mice (n = 8/group) were randomly assigned to 5 diets: unpurified diet with cellulose (4%; control), corn-derived hydroxypropylated new resistant starch (NRS) (2% NRS + 2% cellulose), soluble fiber dextrin from tapioca (SFD-t) (4%), soluble fiber dextrin from corn (SFD-c) (4%), or soluble corn fiber (4%) for 12 wk. Growth, small intestinal permeability, histologic injury, intestinal cytokine secretion, and microbiota composition by 16S ribosomal RNA pyrosequencing of stool were measured. ANOVA and principal component analysis were applied to assess the fibers' effects., Results: There were no significant differences in mouse growth, intestinal weight, length, or gut permeability over the 12 wk feeding period. Mice fed dextrin-based diets secreted 47-88% less colonic IL-1β, tumor necrosis factor α, and IL-23 (SFD-t diet) and IL-12 heterodimer p70, IL-6, and chemokine ligand 1 (CXCL1) (SFD-c diet) (P < 0.05) than did the control group, whereas NRS-fed mice secreted 55-77% less IL-6 and CXCL1 (P < 0.05). Both SFD-t- and SFD-c-fed mice had a 70-75% lower abundance of Lactobacillaceae than control mice. The SFD-t diet group had a lower enterocyte injury score (P < 0.04) than did control mice, and this was associated with increased abundance of butyrate producers, including Incertae sedis XIV, Lachnospiraceae, and Ruminococcaceae (P < 0.001)., Conclusions: These results demonstrate that soluble prebiotic fibers selectively stimulate the growth of a distinctive gut microbiota in IL-10(-/-) mice. SFD-t induced the growth of butyrate-producing microbes and was effective in reducing proinflammatory cytokine secretion and enterocyte injury in this mouse model of colitis., (© 2015 American Society for Nutrition.)

Background & Aims: Probiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn's disease after surgery. We investigated the ability of VSL#3, a mixture of 8 different bacterial probiotic species, to prevent Crohn's disease recurrence after surgery in a multicenter, randomized, double-blind, placebo-controlled trial., Methods: Within 30 days of ileocolonic resection and re-anastomosis, patients with Crohn's disease were randomly assigned to groups given 1 sachet of VSL#3 (900 billion viable bacteria, comprising 4 strains of Lactobacillus, 3 strains of Bifidobacterium, and 1 strain of Streptococcus salivarius subspecies thermophilus) (n = 59) or matching placebo (n = 60). Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis. Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365. The primary outcome was the proportion of patients with severe endoscopic recurrence at day 90., Results: At day 90, the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 (9.3%) and placebo (15.7%, P = .19). The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0% in the early VSL#3 group (given VSL#3 for the entire 365 days) and 26.7% in the late VSL#3 group (given VSL#3 from days 90 through 365) (P = .09). Aggregate rates of severe recurrence (on days 90 and 365) were not statistically different, 20.5% of subjects in the early VSL#3 group and 42.1% in the late VSL#3 group. Patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared with placebo at day 90 (P < .05). Crohn's disease activity index and inflammatory bowel disease quality of life scores were similar in the 2 groups., Conclusions: There were no statistical differences in endoscopic recurrence rates at day 90 between patients who received VSL#3 and patients who received placebo. Lower mucosal levels of inflammatory cytokines and a lower rate of recurrence among patients who received early VSL#3 (for the entire 365 days) indicate that this probiotic should be further investigated for prevention of Crohn's disease recurrence. Clinical trials.gov number: NCT00175292., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine of unclear etiology. Increasing evidence has pointed to intestinal dysbiosis as a potential factor in a genetically susceptible individual. Fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease with variable degrees of success. Herein, we report a patient with Crohn's colitis, previously failing an immunosuppressant, who achieved clinical, endoscopic, and histologic remission after a single fecal microbiota transplantation infusion. We have further characterized the changes in the fecal microbiota associated with this observation.

As human civilization is becoming more aware of the negative impact our actions can inflict upon the natural world, the intensification of fossil fuel extraction and industrial development is being met with increasing opposition. In Western Canada, proposals that would increase the volume of petroleum transported by pipelines and by tankers through the coastal waters of British Columbia have engaged the province in debate. To ease public concern on the risk of a coastal oil spill, there are additional commitments that involved parties could make. There is evidence to show that the practice of registering vessels under foreign flags of states that have exhibited failure in compliance with international obligations is more common amongst petroleum tankers that have been involved in large-scale oil spills. To prove that they are committed to reducing the risk of oil spills, businesses need to stop registering their vessels under flags of foreign, non-compliant states., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background & Aims: In patients with decompensated cirrhosis, bacterial translocation can contribute to splanchnic vasodilatation, decreased effective circulating volume, and portal hypertension. The primary objective of this randomized, double blind placebo controlled trial was to evaluate the effect of the probiotic VSL#3(®) on the hepatic venous pressure gradient (HVPG)., Methods: Seventeen patients with decompensated cirrhosis and an HVPG of ≥ 10 mmHg were randomized to receive 2 months of VSL#3(®) or an identical placebo. HVPG, endotoxin, interleukin (IL)-6, IL-8, IL-10, renin, aldosterone, nitric oxide and stool microbiota were measured at baseline and study end., Results: Two of the 17 patients were taken off the trial before completion (one for alcohol abuse and the second for SBP - both in placebo arm). Data were analysed on the remaining 15 patients. The median model for end-stage liver disease score was 12, and 80% of patients had Child Pugh B disease. The treatment arm had a greater decrease in HVPG from baseline to study end than the placebo arm (median change from baseline -11.6% vs +2.8%), although this reduction was not statistically significant in either group. There was a significant reduction in the plasma aldosterone level in the VSL#3(®) group, but no significant changes in the other measured parameters, including the stool microflora analysis., Conclusions: Within the limitations of our sample size, VSL#3(®) therapy does not appear to have a significant impact on portal pressure reduction in patients with decompensated cirrhosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)