In the last 30 years, non‐celiac gluten sensitivity (NCGS) has emerged as an intriguing and controversial topic in gastroenterology. The diagnosis of NCGS/NCWS requires a symptomatic reaction to ...gluten, or wheat‐containing food, and remission of symptoms with gluten or wheat challenge, in patients in whom celiac disease and wheat allergy have been excluded. There have been several randomized clinical trials (RCT) addressing this issue which have produced controversial results. In this issue of Neurogastroenterology and Motility, a double‐blind placebo‐controlled randomized trial in patients with suspected NCGS on GFD, did not reproduce symptoms after gluten intake compared to placebo. This mini‐review addresses outstanding issues related to the diagnosis of NCGS/NCWS as well as areas of interest for future studies that could explain, in part, the controversy in this area.
Alterations in the intestinal microbiota, characterized by depletion of anti-inflammatory bacteria, such as Firmicutes, in patients with ulcerative colitis (UC) have prompted interest in ...microbiota-modulating strategies for this condition. The aim of this study was to evaluate the role of fecal and synthetic human microbial ecosystems, low or enriched in Firmicutes, on colitis susceptibility and host immune responses.
The microbiota of selected healthy and UC human donors was characterized by culture method and 16S rRNA-based sequencing. Germ-free mice were colonized with fecal or a synthetic ecosystem enriched (healthy donors) or low (UC donors) in Firmicutes. Experimental colitis was induced using dextran sodium sulfate. Colon transcriptome and colon lamina propria cells were evaluated in mice postcolonization by RNA-seq and flow cytometry, respectively, and T helper (TH) 17 differentiation was assessed in vitro.
Mice colonized with microbiota from patients with UC low in Firmicutes had increased sensitivity to colitis compared with mice colonized with fecal or synthetic ecosystems rich in Firmicutes. Microbiota low in Firmicutes increased expression of TH17-related genes and expansion of interleukin-17A-expressing CD4 cells in vivo. Supplementation with bacterial isolates belonging to the Firmicutes phylum abrogated the heightened TH17 responses in vitro.
A microbiota rich in Firmicutes derived from fecal samples of a healthy human donor, or assembled synthetically, downregulated colonic inflammation and TH17 pathways in mice. The results support the use of ecobiotherapy strategies, enriched in Firmicutes, for the prevention or treatment of UC.
We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) ...patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity.
To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD).
Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies.
We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001).
The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.
Gluten free diet is the only available treatment for celiac disease (CeD). Patients with CeD who do not adhere to a strict gluten-free diet (GFD) have been found to have complications involving ...nutritional deficiencies, increased risk of bone fractures, increased risk of mortality, and certain types of cancers. Complete removal of gluten from the diet in a patient with CeD often results in symptomatic, serologic, and histologic remission. However, strict compliance with the diet is challenging. Long-term follow-up care is needed to assure treatment compliance and positive health outcomes. Monitoring celiac specific serology, nutrient deficiencies, bone mineral density, and assessment of GFD compliance have been recommended in clinical practice. However, there is no consensus on which specific tests and how often they should be performed during the follow up. Here, we have performed a review of the literature on current strategies to follow up patients with CeD. There are new tools for monitoring adherence to the GFD which could change some paradigms in following up treated patients.
Background & Aims. Postoperative weight loss is common following hepato-pancreato-biliary (HPB) surgical resections; however, the extent of weight loss and the association with poor outcomes have not ...been well described. We assessed the average percentage of weight loss and risk factors associated with sustained postoperative weight loss. Materials and Methods. We enrolled patients undergoing major HPB surgical resections from 2011–2016 at a single institution. We evaluated percent change in weight postoperatively, incidence of complications, and nutritional clinical markers at 1, 3, and 6 months postoperatively compared to preoperative baseline. We used multiple logistic regression to evaluate factors associated with significant weight loss (>10% from baseline) at 3 months from surgery. Results. Among 262 patients undergoing HPB surgery, liver surgery patients lost 2.5% of baseline weight at 3 months postoperatively but regained baseline weight by 6 months. Pancreatic surgery patients lost 7.7% at 3 months and were unable to recover their baseline weights at 6 months. Forty-three (16%) patients had major postoperative complications including abdominal abscess (5.3%) and anastomotic leak (3.8%). Patients who experienced major postoperative complications had a greater percentage weight loss at 3 months compared to those without major complications: median 11% (interquartile range (IQR): 7%–15%) vs 4% (IQR: 0%–8%), P < .001. In the multivariable analysis, major postoperative complications were associated with significant weight loss at 3 months (OR 3.39, 95% CI 1.38–8.33). Conclusions. Due to the association of weight loss and major postoperative complications, patients who experience significant weight loss (>10% from baseline) may benefit from nutritional assessment for dietary intervention.
Open-air composting evolution of domestic solid wastes (DSW) collected during 150 days from a neighborhood of Santiago del Estero, Argentina, was investigated using several standard methods of ...compost analysis, in combination with steady-state UV–Vis absorption and fluorescence measurements of their extracted total humic substance-like (HSL), fulvic acid-like (FAL), and humic acid-like (HAL) molecules. The UV-spectra of the HSL were fitted with a two Gaussian-like bands model, allowing the calculation of the absorption ratio between the electron-transfer and benzenoid band components,
A
o,ET/
A
o,Bz, which provided information about the type and degree of substitution into the aromatic chromophores. In addition, the variation of the absorbance ratio E
4/E
6 of the HSL was mainly sensitive to the fraction of FAL substances. Fluorescence quantum yields (
Φ
F) and full-width at half-maximum (FWHM) for the different humic extracts were also valuable parameters for tracking the evolution of these substances during composting. The excitation–emission matrix (EEM) of the different extracts showed the presence of two fluorescence maxima, namely P1 (
λ
exc
<
280 nm) and P2 (
λ
exc
>
280 nm) respectively. Only the location of the P2 of HAL was sensitive to the evolution of composting, indicating the continuous modification of the fluorophore during the process.
The present results indicate the suitability of combined absorption and emission spectroscopical properties in the characterization of both HSL and evolution of composting.
There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled ...trials (RCTs) in this population is lacking.
A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale.
For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal–sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points.
We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
An expert panel of gastroenterologists and pathologists established recommendations for the design of clinical trials evaluating new drugs for the treatment of celiac disease in adults, adolescents, and children.
Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid ...conditions is unknown.
To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis.
This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group.
A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett's esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (
< 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%;
< 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality
< 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (
< 0.02).
In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.
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