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Single strain versus multispecies probiotic on necrotizing enterocolitis and faecal IgA levels in very low birth weight preterm neonates: A randomized clinical trial.
Gómez-Rodríguez, G, Amador-Licona, N, Daza-Benítez, L, Barbosa-Sabanero, G, Carballo-Magdaleno, D, Aguilar-Padilla, R, González-Ramirez, E
Pediatrics and neonatology. 2019;(5):564-569
Abstract
BACKGROUND According to the literature, probiotics are an attractive alternative to prevent necrotizing enterocolitis (NEC). However, due to differences in probiotic composition, randomized controlled trials are necessary to compare different probiotic mixtures. The objective of this study was to compare single strain (Lactobacillus acidophilus boucardii) versus multispecies probiotics on NEC incidence and faecal secretory Immunoglobulin A (sIgA) levels in very low preterm newborns. METHODS We performed a double-blind randomized trial in 90 newborns. L. acidophilus boucardii strain or multispecies probiotics were randomly assigned to preterm newborns. As the primary outcome, we evaluated NEC incidence on the total length of neonatal intensive care unit (NICU) stay. As the secondary outcome, we measured the change in faecal sIgA levels from baseline to 3 weeks following the use of probiotics. RESULTS NEC incidence was similar between groups (0% vs. 2.2% for the single strain and multispecies probiotic, respectively). Faecal sIgA levels increased significantly (p < 0.001) within groups (31% for single strain and 47% for multispecies probiotic), but this increase was not different between groups. Neonates with a faecal sIgA level increment >0.45 mg/dl showed higher gestational age, birth weight, and weight at the second and third weeks of follow up than neonates with a faecal sIgA level increment ≤0.45 mg/dl. No adverse effects were found after probiotics use. CONCLUSIONS No difference between strains of probiotics used was found on NEC incidence or in the increase of faecal sIgA levels. Faecal sIgA levels were positively related to gestational age and body weight in very low preterm infants. ClinicalTrials.gov/NCT02245815.
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Rectal swabs are a reliable proxy for faecal samples in infant gut microbiota research based on 16S-rRNA sequencing.
Reyman, M, van Houten, MA, Arp, K, Sanders, EAM, Bogaert, D
Scientific reports. 2019;(1):16072
Abstract
Rectal swabs are potentially a valuable method for monitoring the gut microbiome in research and clinical settings, where it is important to adhere to strict timing, or where acute sampling is needed. It is currently unknown whether rectal swabs give comparable results to faecal samples regarding microbiota community composition in neonates and infants. To study how well the two sampling methods correlate in infants, we compared the 16S-rRNA-based sequencing results of 131 paired rectal swabs and faecal samples collected from 116 infants at two timepoints in early life. The paired samples were highly comparable regarding both diversity and overall community composition, and strongly correlated on taxonomical level. We observed no significant nor relevant contribution of sampling method to the variation in overall gut microbiota community composition in a multivariable model. Our study provides evidence supporting the use of rectal swabs as a reliable proxy for faecal samples in infant gut microbiota research.
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Effect of administering kefir on the changes in fecal microbiota and symptoms of inflammatory bowel disease: A randomized controlled trial.
Yılmaz, İ, Dolar, ME, Özpınar, H
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2019;(3):242-253
Abstract
BACKGROUND/AIMS: Kefir is a kind of fermented probiotic dairy product. The objective of the present study was to investigate the effects of kefir consumption on the fecal microflora and symptoms of patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS Kefir was serially diluted and inoculated into de Man, Rogosa, and Sharpe agar and incubated at 37°C for 48 to 72 h under anaerobic conditions. This was a single-center, prospective, open-label randomized controlled trial. Forty-five patients with IBD were classified into two groups: 25 for treatment and 20 for control. A 400 mL/day kefir was administered to the patients for 4 weeks day and night. Their stool Lactobacillus, Lactobacillus kefiri, content was quantitated by real-time quantitative polymerase chain reaction before and after consumption. Abdominal pain, bloating, stool frequency, stool consistency, and feeling good scores were recorded in diaries daily by the patients. RESULTS A 5×107 CFU/mL count of lactic acid bacteria colony forming units was found in a kefir sample as the total average count. Lactobacillus bacterial load of feces of all subjects in the treatment group was between 104 and 109 CFU/g, and the first and last measurements were statistically significant (p=0.001 in ulcerative colitis and p=0.005 in Crohn's disease (CD)). The L. kefiri bacterial load in the stool of 17 subjects was measured as between 104 and 106 CFU/g. For patients with CD, there was a significant decrease in erythrocyte sedimentation rate and C-reactive protein, whereas hemoglobin increased, and for the last 2 weeks, bloating scores were significantly reduced (p=0.012), and feeling good scores increased (p=0.032). CONCLUSION According to our data, kefir consumption may modulate gut microbiota, and regular consumption of kefir may improve the patient's quality of life in the short term.
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Pomegranate juice to reduce fecal calprotectin levels in inflammatory bowel disease patients with a high risk of clinical relapse: Study protocol for a randomized controlled trial.
Scaioli, E, Belluzzi, A, Ricciardiello, L, Del Rio, D, Rotondo, E, Mena, P, Derlindati, E, Danesi, F
Trials. 2019;(1):327
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes of intestinal inflammation and is thought to be related to an autoimmune reaction to genetic and environmental factors. Although evidence indicates that a polyphenolic-rich diet plays an important role in modulating aspects of chronic inflammation, few studies have focused on the effect of ellagitannin (ET)-rich food consumption on long-term remission maintenance in IBD patients with a high risk of clinical relapse. Therefore, we hypothesize that supplementation with a pomegranate juice, a naturally rich source of ETs, could significantly modulate the markers of mucosal and systemic inflammation relative to a control group receiving a placebo. METHODS/DESIGN This double-blind, randomized controlled trial includes patients with IBD involving the colorectum who have been in stable therapy for at least the three previous months and have a high risk of clinical relapse. Participants are randomly allocated to one of two groups: active supplementation (125 mL of cv. Wonderful pomegranate juice) or placebo (125 mL) taken twice daily for 12 weeks. The primary outcome is changes in the fecal neutrophil-derived protein calprotectin, a surrogate marker of mucosal improvement, between the two groups from baseline to 12 weeks later. The secondary outcomes include transcriptomic changes in peripheral blood mononuclear cells and intestinal biopsies and changes in circulating inflammatory markers and trimethylamine-N-oxide levels. Pomegranate ET-derived metabolites are identified and quantified in plasma and urine samples. DISCUSSION The results will provide information on the possible reduction of fecal calprotectin levels following the consumption of pomegranate juice. The findings will also show the in vivo metabolism of pomegranate ETs. Finally, the effect of 12-week pomegranate juice consumption on local and systemic inflammatory markers will be elucidated, which will likely provide additional insights into the maintenance of remission in IBD patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT03000101 . Registered on 21 December 2016.
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Modification of wheat bran particle size and tissue composition affects colonisation and metabolism by human faecal microbiota.
De Paepe, K, Verspreet, J, Rezaei, MN, Martinez, SH, Meysman, F, Van de Walle, D, Dewettinck, K, Courtin, CM, Van de Wiele, T
Food & function. 2019;(1):379-396
Abstract
Dietary modulation can alter the gut microbiota composition and activity, in turn affecting health. Particularly, dietary fibre rich foods, such as wheat bran, are an important nutrient source for the gut microbiota. Several processing methods have been developed to modify the functional, textural and breadmaking properties of wheat bran, which can affect the gut microbiota. We therefore studied the effect of enzyme treatment, particle size reduction and wheat kernel pearling on the faecal microbiota of ten healthy individuals. The most commonly studied health marker, associated to the gut microbiota activity is Short Chain Fatty Acid (SCFA) production. This study shows that modifying wheat bran physicochemical properties allows control over the extent and the rate of SCFA production by the faecal microbiota. Wheat bran pericarp fractions, depleted in starch and enriched in cellulose and highly branched arabinoxylans, were poorly fermentable compared to unmodified wheat bran, thus resulting in a reduced SCFA production with up to 20 mM. The nature of the SCFA, however, largely depends on the donor and can be linked to the individual's gut microbiota composition. The latter changed in an individually dependent manner in response to wheat bran modification. Some product dependent significant differences could still be identified across the ten donors. This product effect is more pronounced in the microbial community attached to the wheat bran residue as compared to the luminal microbial community. Generally, we find lower levels of Firmicutes, Bacteroidetes and Bifidobacterium and a higher abundance of Proteobacteria in the pericarp enriched wheat bran fractions, compared to unmodified wheat bran.
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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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Fecal Microbiotas of Indonesian and New Zealand Children Differ in Complexity and Bifidobacterial Taxa during the First Year of Life.
Lawley, B, Otal, A, Moloney-Geany, K, Diana, A, Houghton, L, Heath, AM, Taylor, RW, Tannock, GW
Applied and environmental microbiology. 2019;(19)
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Abstract
The biological succession that occurs during the first year of life in the gut of infants in Western countries is broadly predictable in terms of the increasing complexity of the composition of microbiotas. Less information is available about microbiotas in Asian countries, where environmental, nutritional, and cultural influences may differentially affect the composition and development of the microbial community. We compared the fecal microbiotas of Indonesian (n = 204) and New Zealand (NZ) (n = 74) infants 6 to 7 months and 12 months of age. Comparisons were made by analysis of 16S rRNA gene sequences and derivation of community diversity metrics, relative abundances of bacterial families, enterotypes, and cooccurrence correlation networks. Abundances of Bifidobacterium longum subsp. infantis and B. longum subsp. longum were determined by quantitative PCR. All observations supported the view that the Indonesian and NZ infant microbiotas developed in complexity over time, but the changes were much greater for NZ infants. B. longum subsp. infantis dominated the microbiotas of Indonesian children, whereas B. longum subsp. longum was dominant in NZ children. Network analysis showed that the niche model (in which trophic adaptation results in preferential colonization) of the assemblage of microbiotas was supported in Indonesian infants, whereas the neutral (stochastic) model was supported by the development of the microbiotas of NZ infants. The results of the study show that the development of the fecal microbiota is not the same for infants in all countries, and they point to the necessity of obtaining a better understanding of the factors that control the colonization of the gut in early life.IMPORTANCE This study addresses the microbiology of a natural ecosystem (the infant bowel) for children in a rural setting in Indonesia and in an urban environment in New Zealand. Analysis of DNA sequences generated from the microbial community (microbiota) in the feces of the infants during the first year of life showed marked differences in the composition and complexity of the bacterial collections. The differences were most likely due to differences in the prevalence and duration of breastfeeding of infants in the two countries. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of nutrition and environment on the development of the gut microbiota and for determining the long-term effects of microbiological events in early life on human health and well-being.
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Growth, stool consistency and bone mineral content in healthy term infants fed sn-2-palmitate-enriched starter infant formula: A randomized, double-blind, multicentre clinical trial.
Béghin, L, Marchandise, X, Lien, E, Bricout, M, Bernet, JP, Lienhardt, JF, Jeannerot, F, Menet, V, Requillart, JC, Marx, J, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(3):1023-1030
Abstract
BACKGROUND Palmitate in breast milk is predominantly located in the triacylglycerol sn-2 position, while infant formulae contain palmitate predominantly in the sn-1 and sn-3 positions. During digestion, palmitate in the sn-1 and sn-3 positions is hydrolyzed to free palmitic acid that can subsequently complex with calcium to form insoluble soaps; this may partially explain why formula-fed infants have harder stools than breast-fed infants. METHODS This large (n = 488) randomized, double-blind, multicentre trial investigated whether increasing the sn-2 palmitate content of infant formula improves stool consistency and bone mineral content (measured by dual-energy x-ray absorptiometry), without affecting growth or health. From ∼1 week to 4 months of age, infants were exclusively fed one of three formulae: i) control formula (CF; 16% of total palmitate at sn-2; n = 162), (ii) experimental formula 1 (EF1; 43% of total palmitate at sn-2; n = 166) or (iii) experimental formula 2 (EF2; 51% of total palmitate at sn-2; n = 160). RESULTS Intention-to-treat analysis showed softer stools in both EF groups (vs. CF) at ages 2 weeks and 1 and 2 months (p ≤ 0.01), but not 3 and 4 months. At 4 months, all groups had similar growth outcomes while bone mineral content was significantly higher in EF1 (p = 0.0012) and EF2 (p = 0.0002) compared with CF. Comparison of reported adverse events up to 12 months revealed no differences among groups. All 3 infant formulae exhibited equally good digestive tolerance. CONCLUSIONS Formulae enriched in sn-2 palmitate fed in early infancy are safe, improve stool consistency (from 2 weeks to 2 months) and increase bone mineral content (at 4 months).
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Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction.
Mondal, P, Long, JM, Westcott, JE, Islam, MM, Ahmed, M, Mahfuz, M, Ahmed, T, Miller, LV, Krebs, NF
Journal of pediatric gastroenterology and nutrition. 2019;(6):874-879
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Abstract
OBJECTIVES Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M). METHODS Bangladeshi toddlers (18-24 months) with low (<0.09) and high (≥0.09) L:M were administered isotope-labeled 3 mg aqueous zinc in the fasted state. Fractional absorption of zinc (FAZ) and EFZ were measured by dual stable isotope tracer method and an isotope dilution method, respectively. Secondary aims included examining relationships of biomarkers of systemic and intestinal inflammation and gut function with FAZ and EFZ. RESULTS Forty children completed the study; nearly all had evidence of EED. No differences in zinc homeostasis measurements (mean ± SD) were observed between high and low L:M groups: FAZ was 0.38 ± 0.19 and 0.31 ± 0.19, respectively; both figures were within estimated reference range. Means of EFZ were 0.73 ± 0.27 and 0.76 ± 0.20 mg/day for high and low L:M, respectively, and were 10% to 15% above estimated reference range. Regression analyses indicated that biomarkers of systemic inflammation were directly associated with increasing FAZ, consistent with increased gut permeability. Biomarkers of intestinal inflammation were negatively associated with EFZ, consistent with low-zinc intake and chronic deficiency. CONCLUSIONS In these children at risk of EED, endogenous zinc losses were not markedly increased. Results suggest that efforts to improve zinc status in EED should focus on substantially improving zinc intakes.
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Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients.
Foster, AJ, Smyth, M, Lakhani, A, Jung, B, Brant, RF, Jacobson, K
World journal of gastroenterology. 2019;(10):1266-1277
Abstract
BACKGROUND Asymptomatic children with Crohn's disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation. AIM: In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse. METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo. RESULTS 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 μg/g (283-1758) vs 244 μg/g (61-627), P = 0.02]. Fecal calprotectin levels > 250 μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937). CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.