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The Efficacy of Probiotics, Prebiotic Inulin-Type Fructans, and Synbiotics in Human Ulcerative Colitis: A Systematic Review and Meta-Analysis.
Astó, E, Méndez, I, Audivert, S, Farran-Codina, A, Espadaler, J
Nutrients. 2019;11(2)
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It is thought that ulcerative colitis (UC) may be caused by an excessive immune response to endogenous bacteria in genetically predisposed individuals, and therefore that manipulating of the gut flora may be of benefit. Microbial diversity and intestinal microbiota stability are lower in patients with inflammatory bowel disease (including UC), than in healthy people. This systematic review and metanalysis looked at clinical trials using probiotics, prebiotics and synbiotics (a combination of pro- and prebiotics) in UC. 18 papers were included, with a total of 1491 adult and 69 children. 16 of these were on probiotics, one on prebiotics and one on synbiotics. Outcomes considered in this systematic review were the effects on short chain fatty acids (SCFAs, metabolic end products of gut bacteria which have a beneficial effect on immune and gut health), inflammation levels, composition of faecal microbiota and UC remission. In trials on inactive UC patients, the faecal concentration of SCFAs did not differ significantly between the probiotic and placebo groups, whilst in trials with active UC patients, SCFAs significantly increased after probiotic supplementation. All studies reported a significant reduction in inflammation. Meta-analysis of studies which looked at induction/maintenance of remission by probiotics showed that this depends on a) the type of disease activity score used to assess remission, and b) the type of probiotics used, with bifidobacteria containing probiotics, VSL3 and Mutaflor showing benefits, but studies without bifidobacteria being no different from placebo. The authors conclude that bifidobacteria containing probiotics seem to be beneficial in terms of reaching remission in patients with UC, although there is insufficient information on necessary dose and duration of treatment. They note that there are only few studies on prebiotics and synbiotics and are calling for a standardisation of scales to assess remission.
Abstract
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13⁻2.15, p-value = 0.007, I² = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23⁻2.43, p-value = 0.002, I² = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
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I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life.
Lorenzo-Zúñiga, V, Llop, E, Suárez, C, Alvarez, B, Abreu, L, Espadaler, J, Serra, J
World journal of gastroenterology. 2014;(26):8709-16
Abstract
AIM: To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). METHODS A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. RESULTS During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. CONCLUSION A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea.
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A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial.
Mañé, J, Pedrosa, E, Lorén, V, Gassull, MA, Espadaler, J, Cuñé, J, Audivert, S, Bonachera, MA, Cabré, E
Nutricion hospitalaria. 2011;(1):228-35
Abstract
BACKGROUND & AIM: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum--CECT 7315 and 7316--on systemic immunity in elderly. METHODS 50 institutionalized elderly subjects were randomized, in a double-blind fashion, to receive for 12 weeks 1) 5·10(8) cfu/day of L. plantarum CECT7315/7316 ("low probiotic dose") (n = 13), 2) 5·10(9) cfu/day of the probiotic mixture ("high probiotic dose") (n = 19), or 3) placebo (n = 15). Leukocyte subpopulations, and cytokine levels (IL-1 , IL-10, TGF-β1) were measured in venous blood at baseline, end of treatment (week 12), and end of follow-up (week 24). Infection and survival rates were recorded. RESULTS After treatment, high probiotic dose resulted in significant increases in the percentages of activated potentially T-suppressor (CD8+CD25+) and NK (CD56+ CD16+) cells, while low probiotic dose increased activated T-helper lymphocytes (CD4+CD25+), B lymphocytes (CD19+), and antigen presenting cells (HLA-DR+). Also, plasma TGF-β1 concentration significantly decreased after treatment with both probiotic doses. Most of these changes remained 12 weeks after probiotic discontinuation. Incidence of infections during treatment showed a significant trend to be lower in the high probiotic dose group. In addition, there was a significant trend for mortality to be greater in the placebo group vs. both probiotic groups. CONCLUSIONS Depending on the dose, L. plantarum CECT7315/7316 have different immune-enhancing effects in elderly subjects. These effects might result in a better clinical outcome.
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Prediction of enzyme function by combining sequence similarity and protein interactions.
Espadaler, J, Eswar, N, Querol, E, Avilés, FX, Sali, A, Marti-Renom, MA, Oliva, B
BMC bioinformatics. 2008;:249
Abstract
BACKGROUND A number of studies have used protein interaction data alone for protein function prediction. Here, we introduce a computational approach for annotation of enzymes, based on the observation that similar protein sequences are more likely to perform the same function if they share similar interacting partners. RESULTS The method has been tested against the PSI-BLAST program using a set of 3,890 protein sequences from which interaction data was available. For protein sequences that align with at least 40% sequence identity to a known enzyme, the specificity of our method in predicting the first three EC digits increased from 80% to 90% at 80% coverage when compared to PSI-BLAST. CONCLUSION Our method can also be used in proteins for which homologous sequences with known interacting partners can be detected. Thus, our method could increase 10% the specificity of genome-wide enzyme predictions based on sequence matching by PSI-BLAST alone.
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Identification of function-associated loop motifs and application to protein function prediction.
Espadaler, J, Querol, E, Aviles, FX, Oliva, B
Bioinformatics (Oxford, England). 2006;(18):2237-43
Abstract
MOTIVATION The detection of function-related local 3D-motifs in protein structures can provide insights towards protein function in absence of sequence or fold similarity. Protein loops are known to play important roles in protein function and several loop classifications have been described, but the automated identification of putative functional 3D-motifs in such classifications has not yet been addressed. This identification can be used on sequence annotations. RESULTS We evaluated three different scoring methods for their ability to identify known motifs from the PROSITE database in ArchDB. More than 500 new putative function-related motifs not reported in PROSITE were identified. Sequence patterns derived from these motifs were especially useful at predicting precise annotations. The number of reliable sequence annotations could be increased up to 100% with respect to standard BLAST. CONTACT boliva@imim.es SUPPLEMENTARY INFORMATION Supplementary Data are available at Bioinformatics online.
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Detecting remotely related proteins by their interactions and sequence similarity.
Espadaler, J, Aragüés, R, Eswar, N, Marti-Renom, MA, Querol, E, Avilés, FX, Sali, A, Oliva, B
Proceedings of the National Academy of Sciences of the United States of America. 2005;(20):7151-6
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Abstract
The function of an uncharacterized protein is usually inferred either from its homology to, or its interactions with, characterized proteins. Here, we use both sequence similarity and protein interactions to identify relationships between remotely related protein sequences. We rely on the fact that homologous sequences share similar interactions, and, therefore, the set of interacting partners of the partners of a given protein is enriched by its homologs. The approach was bench-marked by assigning the fold and functional family to test sequences of known structure. Specifically, we relied on 1,434 proteins with known folds, as defined in the Structural Classification of Proteins (SCOP) database, and with known interacting partners, as defined in the Database of Interacting Proteins (DIP). For this subset, the specificity of fold assignment was increased from 54% for position-specific iterative BLAST to 75% for our approach, with a concomitant increase in sensitivity for a few percentage points. Similarly, the specificity of family assignment at the e-value threshold of 10(-8) was increased from 70% to 87%. The proposed method would be a useful tool for large-scale automated discovery of remote relationships between protein sequences, given its unique reliance on sequence similarity and protein-protein interactions.