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1.
Alterations in fecal short-chain fatty acids in patients with irritable bowel syndrome: A systematic review and meta-analysis.
Sun, Q, Jia, Q, Song, L, Duan, L
Medicine. 2019;(7):e14513
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Abstract
BACKGROUND Recent studies indicate that gut microbiota disorders potentially contribute to the pathogenesis of irritable bowel syndrome (IBS), which can be partly reflected by fecal short-chain fatty acids (SCFAs) generated from gut microbiota. Previous studies on SCFA alterations in patients with IBS have yielded conflicting results. No prior systematic review has been conducted on the alterations in fecal SCFAs in IBS patients. AIMS We performed a meta-analysis to explore and clarify alterations in fecal SCFAs in IBS patients. METHODS Case-control studies, randomized controlled trials (RCTs), and self-controlled studies were identified through electronic database searches. The standardized mean difference (SMD) with 95% confidence interval (CI) in fecal SCFA levels between different groups was calculated. RESULTS The proportion of fecal propionate in patients with IBS was significantly higher than in healthy controls (HCs) (SMD = 0.44, 95% CI = 0.12, 0.76). A subgroup analysis showed that the concentration of fecal propionate (SMD = -0.91, 95% CI = -1.41, -0.41) and butyrate (SMD = -0.53, 95% CI = -1.01, -0.04) in patients with constipation-predominant IBS (IBS-C) was significantly lower than that in HCs, and the concentration of fecal butyrate in patients with diarrhea-predominant IBS (IBS-D) was higher than that in HCs (SMD = 0.34, 95% CI = 0.00, 0.67). Finally, we found that restricted diets correlated with fecal butyrate reduction in IBS (SMD = -0.26, 95% CI = -0.51, -0.01). CONCLUSIONS In terms of fecal SCFAs, there were differences between patients with IBS and HCs. In IBS-C patients, propionate and butyrate were reduced, whereas butyrate was increased in IBS-D patients in comparison to HCs. Propionate and butyrate could be used as biomarkers for IBS diagnosis.
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Short Chain Fatty Acids and Fecal Microbiota Abundance in Humans with Obesity: A Systematic Review and Meta-Analysis.
Kim, KN, Yao, Y, Ju, SY
Nutrients. 2019;(10)
Abstract
There have been mixed results regarding the relationship among short chain fatty acids (SCFAs), microbiota, and obesity in human studies. We selected studies that provided data on SCFA levels or fecal microbiota abundance in obese and nonobese individuals and then combined the published estimates using a random-effects meta-analysis. Obese individuals had significantly higher fecal concentrations of acetate (SMD (standardized mean differences) = 0.87, 95% CI (confidence interva) = 0.24-1.50, I2 (I-squared) = 88.5), propionate (SMD = 0.86, 95% CI = 0.35-1.36, I2 = 82.3%), and butyrate (SMD = 0.78, 95% CI = 0.29-1.27, I2 = 81.7%) than nonobese controls. The subgroup analyses showed no evidence of heterogeneity among obese individuals with a BMI >30 kg/m2 (I2 = 0.0%). At the phylum level, the abundance of fecal microbiota was reduced in obese compared to nonobese individuals, but the difference was not statistically significant (Bacteroidetes phylum, SMD = -0.36, 95% CI = -0.73-0.01; Firmicutes phylum, SMD = -0.10, 95% CI = -0.31-0.10). The currently available human case-control studies show that obesity is associated with high levels of SCFA but not gut microbiota richness at the phylum level. Additional well-designed studies with a considerable sample size are needed to clarify whether this association is causal, but it is also necessary to identify additional contributors to SCFA production, absorption, and excretion in humans.
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Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.
Wirbel, J, Pyl, PT, Kartal, E, Zych, K, Kashani, A, Milanese, A, Fleck, JS, Voigt, AY, Palleja, A, Ponnudurai, R, et al
Nature medicine. 2019;(4):679-689
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Abstract
Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10-5). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
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Non-invasive diagnostic tests for Helicobacter pylori infection.
Best, LM, Takwoingi, Y, Siddique, S, Selladurai, A, Gandhi, A, Low, B, Yaghoobi, M, Gurusamy, KS
The Cochrane database of systematic reviews. 2018;(3):CD012080
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Abstract
BACKGROUND Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
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Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials.
de Vries, J, Birkett, A, Hulshof, T, Verbeke, K, Gibes, K
Nutrients. 2016;(3):130
Abstract
Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993.
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Faecal calprotectin in suspected paediatric inflammatory bowel disease.
Degraeuwe, PL, Beld, MP, Ashorn, M, Canani, RB, Day, AS, Diamanti, A, Fagerberg, UL, Henderson, P, Kolho, KL, Van de Vijver, E, et al
Journal of pediatric gastroenterology and nutrition. 2015;(3):339-46
Abstract
OBJECTIVES The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data. METHODS MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator. RESULTS According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94). CONCLUSIONS In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.
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C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis.
Mosli, MH, Zou, G, Garg, SK, Feagan, SG, MacDonald, JK, Chande, N, Sandborn, WJ, Feagan, BG
The American journal of gastroenterology. 2015;(6):802-19; quiz 820
Abstract
OBJECTIVES Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD. METHODS Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis. RESULTS Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease. CONCLUSIONS Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.
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Fecal lactoferrin in discriminating inflammatory bowel disease from irritable bowel syndrome: a diagnostic meta-analysis.
Zhou, XL, Xu, W, Tang, XX, Luo, LS, Tu, JF, Zhang, CJ, Xu, X, Wu, QD, Pan, WS
BMC gastroenterology. 2014;:121
Abstract
BACKGROUND To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). METHODS The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91). CONCLUSIONS FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.
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Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials.
Christensen, R, Lorenzen, JK, Svith, CR, Bartels, EM, Melanson, EL, Saris, WH, Tremblay, A, Astrup, A
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2009;(4):475-86
Abstract
Observational studies have found that dietary calcium intake is inversely related to body weight and body fat mass. One explanatory mechanism is that dietary calcium increases faecal fat excretion. To examine the effect of calcium from dietary supplements or dairy products on quantitative faecal fat excretion, we performed a systematic review with meta-analysis. We included randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured. Meta-analyses used random-effects models with changes in faecal fat excreted expressed as standardized mean differences, as the studies assessed the same outcome but measured in different ways. An increased calcium intake resulted in increased excretion of faecal fat by a standardized mean difference of 0.99 (95% confidence intervals: 0.63-1.34; P < 0.0001; expected to correspond to approximately 2g day(-1)) with moderate heterogeneity (I(2) = 49.5%) indicating some inconsistency in trial outcomes. However, the dairy trials showed homogeneous outcomes (I(2)=0%) indicating consistency among these trials. We estimated that increasing the dairy calcium intake by 1241 mg day(-1) resulted in an increase in faecal fat of 5.2 (1.6-8.8) g day(-1). In conclusion, dietary calcium has the potential to increase faecal fat excretion to an extent that could be relevant for prevention of weight (re-)gain. Long-term studies are required to establish its potential contribution.