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Effects of probiotics administration on lactose intolerance in adulthood: A meta-analysis.
Ahn, SI, Kim, MS, Park, DG, Han, BK, Kim, YJ
Journal of dairy science. 2023;106(7):4489-4501
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Milk and dairy products are good sources of protein, calcium and other nutrients. However, many people experience lactose intolerance due to their digestive tract's inability to digest lactose, resulting in symptoms such as flatulence, abdominal pain and diarrhoea. Oral administration of certain friendly live microorganisms or probiotics can help digest lactose more efficiently as they have greater β-galactosidase (β-gal) activity. β-galactosidase is an enzyme responsible for the digestion of lactose in the dairy products. A total of twelve studies were included in this meta-analysis. The results of this meta-analysis showed an improvement in the symptoms of lactose intolerance in adult patients, following probiotic administration. Probiotic administration was also found to enhance the digestion of lactose and calcium absorption in adult patients. Healthcare professionals can use the results of this study to understand the potential benefits of oral supplementation of probiotics for adult lactose intolerance patients. However, further studies are needed to understand the relationship between calcium absorption and lactose digestion after probiotic administration.
Abstract
This meta-analysis aimed to investigate the effect of probiotic administration on adults with lactose intolerance. Twelve studies were identified from databases such as PubMed, Cochrane Library, and Web of Knowledge based on the inclusion and exclusion criteria. The effect size was estimated using the standardized mean difference (SMD), and Cochrane's Q test was used to evaluate the statistical heterogeneity of the effect size. Moderator analysis, including meta-ANOVA and meta-regression, were performed to determine the cause of heterogeneity in the effect size using a mixed-effect model. Egger's linear regression test was conducted to evaluate publication bias. The results showed that probiotic administration alleviated the symptoms of lactose intolerance, including abdominal pain, diarrhea, and flatulence. Among them, the area under the curve (AUC) showed the greatest decrease following probiotic administration (SMD, -4.96; 95% confidence interval, -6.92 to -3.00). In the meta-ANOVA test, abdominal pain and total symptoms decreased with monostrain probiotic administration. This combination was also effective for flatulence. The dosage of probiotics or lactose was significantly associated with a reduction in the total symptom score, and the linear regression models between the dosage and SMD were found to be Y = 2.3342 × dosage - 25.0400 (R2 = 79.68%) and Y = 0.2345 × dosage - 7.6618 (R2 = 34.03%), respectively. Publication bias was detected for most items. However, even after effect size correction, the probiotic administration effect for all items remained valid. The administration of probiotics was effective at improving adult lactose intolerance, and it is expected that the results of this study could help improve the nutritional status of adults by increasing their consumption of milk and dairy products in the future.
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Yogurt, cultured fermented milk, and health: a systematic review.
Savaiano, DA, Hutkins, RW
Nutrition reviews. 2021;79(5):599-614
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Many fermented foods are associated with health benefits, including fermented dairy products. Whereby diary itself is part of many nutritional guidelines, the guidances rarely distinguish between dairy and fermented dairy. This qualitative, systematic review sought to capture how consumption of fermented milk products influences health. The review included 108 studies, with over 70% reporting beneficial health outcomes. A small number of studies reported insignificant or neutral results and four unfavourable ones. The aspects of health that were considered included lactose digestion and tolerance, gut health and disease, diarrhoea and constipation, irritable bowel syndrome, cardiovascular health and disease, hypertension, blood lipids, cancer risk, colorectal/breast/prostate cancer, weight and body composition, diabetes risk and metabolic syndrome and bone health. The authors concluded that eating fermented dairy products aided lactose digestion and showed a consistent link with reduced risk of breast and colorectal cancer, type 2 diabetes, and improved weight maintenance, cardiovascular, bone, and gastrointestinal health. As dairy appears to increase the risk for prostate cancer, fermented dairy seems to be no different here to unfermented dairy at increasing the risk. Some potential mechanisms are proposed in the discussion section, how fermented dairy may elicit its health benefits. Given the predominant health benefits of fermented dairy, the authors encouraged to include fermented dairy into national nutrition guidelines and stress distinction between dairy and fermented dairy products. This review captures current evidence of the widespread health benefits of fermented dairy consumption worthwhile considering in clinical practice. In the absence of more clear findings in relation to prostate cancer and prevention, a cautious approach to dairy and fermented dairy consumption may be warranted.
Abstract
Consumption of yogurt and other fermented products is associated with improved health outcomes. Although dairy consumption is included in most dietary guidelines, there have been few specific recommendations for yogurt and cultured dairy products. A qualitative systematic review was conducted to determine the effect of consumption of fermented milk products on gastrointestinal and cardiovascular health, cancer risk, weight management, diabetes and metabolic health, and bone density using PRISMA guidelines. English language papers in PubMed were searched, with no date restrictions. In total, 1057 abstracts were screened, of which 602 were excluded owing to lack of appropriate controls, potential biases, and experimental design issues. The remaining 455 papers were independently reviewed by both authors and 108 studies were included in the final review. The authors met regularly to concur, through consensus, on relevance, methods, findings, quality, and conclusions. The included studies were published between 1979 and 2017. From the 108 included studies, 76 reported a favorable outcome of fermented milks on health and 67 of these were considered to be positive or neutral quality according to the Academy of Nutrition and Dietetics' Quality Criteria Checklist. Of the 32 remaining studies, the study outcomes were either not significant (28) or unfavorable (4), and most studies (18) were of neutral quality. A causal relationship exists between lactose digestion and tolerance and yogurt consumption, and consistent associations exist between fermented milk consumption and reduced risk of breast and colorectal cancer and type 2 diabetes, improved weight maintenance, and improved cardiovascular, bone, and gastrointestinal health. Further, an association exists between prostate cancer occurrence and dairy product consumption in general, with no difference between fermented and unfermented products. This article argues that yogurt and other fermented milk products provide favorable health outcomes beyond the milk from which these products are made and that consumption of these products should be encouraged as part of national dietary guidelines. Systematic review registration: PROSPERO registration no. CRD42017068953.
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Effect of a Preparation of Four Probiotics on Symptoms of Patients with Irritable Bowel Syndrome: Association with Intestinal Bacterial Overgrowth.
Leventogiannis, K, Gkolfakis, P, Spithakis, G, Tsatali, A, Pistiki, A, Sioulas, A, Giamarellos-Bourboulis, EJ, Triantafyllou, K
Probiotics and antimicrobial proteins. 2019;11(2):627-634
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Irritable bowel syndrome (IBS) is the most common functional gut disorder with symptoms primarily of bloating and diarrhea. Recently these symptoms have been associated with small intestinal bacterial overgrowth (SIBO), which occurs when bacteria from the colon resides in the small intestine. The aim of this study was to determine the efficacy of probiotics in improvement of symptoms of IBS patients with SIBO. In this prospective trial, five patients with IBS and SIBO and 21 patients with IBS without SIBO were given probiotic capsules twice a day for 30 days. Participants completed an IBS severity questionnaire at three visits throughout the trial. At the end of the trial, a 71.3% decrease of the total IBS score was detected in patients with IBS and SIBO, compared with those without SIBO. This study found there are clinical benefits from probiotic supplementation in IBS patients with SIBO. Based on these findings, the authors conclude larger, randomised studies be undertaken based on this prospective design.
Abstract
The effect of probiotics on small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) has never been studied so far. In this prospective trial, five patients with IBS and SIBO and 21 patients with IBS without SIBO were administered an oral capsule containing Saccharomyces boulardii, Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus plantarum (Lactolevure®) every 12 h for 30 days. SIBO was defined by quantitative culture of the third part of the duodenum; IBS was defined by the Rome III criteria. Severity of symptoms was graded by the IBS severity scoring system (SSS). The primary study endpoint was the efficacy of probiotics in improvement of symptoms of IBS in patients with SIBO. Thirty days after the end of treatment, a 71.3% decrease of the total IBS score was detected in patients with IBS and SIBO compared to 10.6% in those without SIBO (p 0.017). A similar decrease was achieved among patients with constipation-predominant IBS without SIBO. Post-treatment satisfaction from bowel function was greater in patients with SIBO. Similar satisfaction improvement was found among patients with diarrhea-predominant IBS irrespective from SIBO; pain intensity score decreased in patients with constipation-predominant IBS irrespective from SIBO. The benefit of probiotics was greater among patients with a pro-inflammatory cytokine pattern in the duodenal fluid. This is the first study that prospectively demonstrated superior clinical efficacy of probiotics in patients with IBS with SIBO. Analysis also showed considerable benefit from probiotic intake regarding certain symptoms of patients with diarrhea-predominant and constipation-predominant IBS.Trial registration: ClinicalTrials.gov identifier NCT02204891.
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Disruption of the Gut Ecosystem by Antibiotics.
Yoon, MY, Yoon, SS
Yonsei medical journal. 2018;59(1):4-12
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The gut microbiome is a complex ecosystem of different micro-organisms, such as bacteria, viruses and fungi, living in the human intestines. It’s involved in numerous functions, such as extracting energy and nutrition from food, protecting against disease-causing microorganisms, and supporting the immune system of the host, and therefore affecting human health and disease. This paper is a review of studies on the effects of antibiotics on the gut microbiota. It outlines how different types of antibiotics can alter the intestinal environment and the composition of the microbes, resulting in various physiological changes that can trigger disease. Relevant mechanisms, such as inflammatory response and the use of intestinal nutrients by infectious bacteria are discussed. Finally, it discusses faecal microbiota transplantation (FMT) and probiotics as treatment approaches, aimed at restoring a disturbed intestinal environment.
Abstract
The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.
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Systematic review: probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.
Hungin, APS, Mitchell, CR, Whorwell, P, Mulligan, C, Cole, O, Agréus, L, Fracasso, P, Lionis, C, Mendive, J, Philippart de Foy, JM, et al
Alimentary pharmacology & therapeutics. 2018;47(8):1054-1070
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The role of the gut microbiota in health and disease is far reaching and there is a growing body of evidence on the therapeutic potential of probiotics in gastrointestinal (GI) disease. Patients with GI disease present with a variety of symptoms and current evidence suggests probiotics may play a role in ameliorating these adverse symptoms. The purpose of this review is to update the previous systematic review and incorporate new findings on the role of probiotics in adult patients presenting with a variety of GI symptoms. Based on the updated evidence, this study confirms the finding that specific probiotics are beneficial for certain lower GI problems. According to this review, the author deems this study useful for clinicians when recommending probiotics to patients.
Abstract
BACKGROUND In 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems. AIM: To update the consensus with new evidence. METHODS A systematic review identified randomised, placebo-controlled trials published between January 2012 and June 2017. Evidence was graded, previously developed statements were reassessed by an 8-expert panel, and agreement was reached via Delphi consensus. RESULTS A total of 70 studies were included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea associated with Helicobacter pylori eradication therapy, 7; other conditions, 16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8 reported significant benefits of probiotics vs placebo. Consensus statements with 100% agreement and "high" evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy, and have favourable safety. Statements with 70%-100% agreement and "moderate" evidence indicated that, in some patients with IBS, specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency. CONCLUSIONS This updated review indicates that specific probiotics are beneficial in certain lower GI problems, although many of the new publications did not report benefits of probiotics, possibly due to inclusion of new, less efficacious preparations. Specific probiotics can relieve lower GI symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori eradication therapy, and show favourable safety. This study will help clinicians recommend/prescribe probiotics for specific symptoms.
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Probiotics for prevention of radiation-induced diarrhea: A meta-analysis of randomized controlled trials.
Liu, MM, Li, ST, Shu, Y, Zhan, HQ
PloS one. 2017;12(6):e0178870
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Acute radiation-induced diarrhoea is a potentially fatal side effect of radiotherapy for abdominal or pelvic cancers. The mechanisms are not yet known, but effects of the radiation on the microbiota may be a factor and probiotic treatment may therefore be beneficial. The authors of this meta-analysis looked at randomised controlled trials of probiotics in the prevention of radiation-induced diarrhoea with probiotics (there were not enough trials to evaluate probiotics for the treatment of radiation-induced diarrhoea). Only six studies qualified for inclusion into this meta-analysis, with a total of 917 patients (490 receiving probiotics, 427 controls). Compared with placebo, patients receiving probiotics had a significantly lower risk of developing diarrhoea, but there was no significant reduction in anti-diarrhoea medication use or Bristol scale stool form. Most studies did not report adverse events from probiotic treatment. The meta-analysis was limited by several factors: variety of bacterial strains, dosages and timings used, differences in cancer treatment (dose of radiotherapy, radiotherapy alone or with chemotherapy), variability of patient populations and diseases, and diagnostic criteria for diarrhoea.
Abstract
BACKGROUND Radiotherapy is commonly used for abdominal or pelvic cancer, and patients receiving radiotherapy have a high risk developing to an acute radiation-induced diarrhea. Several previous studies have discussed the effect of probiotics on prevention of radiation-induced diarrhea, but the results are still inconsistent. OBJECTIVE We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of probiotic supplementation for prevention the radiation-induced diarrhea. METHODS Relevant RCTs studies assessing the effect of probiotic supplementation on clinical outcomes compared with placebo were searched in PubMed, EMBASE, and the Cochrane Library databases (up to March 30 2016). Heterogeneity was assessed with I2 and H2, and publication bias was evaluated using sensitive analysis. RESULTS Six trials, a total of 917 participants (490 participants received prophylactic probiotics and 427 participants received placebo), were included in this meta-analysis. Compared with placebo, probiotics were associated with a lower incidence of radiation-induced diarrhea (RR: 0.55; 95% CI: 0.34-0.88; P = 0.01; I2: 87%; 95% CI: 75%-94%; H2: 2.8; 95% CI: 2.0-4.0). However, there is no significant difference in the anti-diarrheal medication use (RR: 0.68; 95% CI: 0.40-1.14; P = 0.14) or bristol scale on stool form (RR: 0.64; 95% CI: 0.35-1.17; P = 0.14). CONCLUSION Probiotics may be beneficial to prevent radiation-induced diarrhea in patients who suffered from abdominal or pelvic cancers during radiotherapy period.
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A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.
Vazquez-Roque, MI, Camilleri, M, Smyrk, T, Murray, JA, Marietta, E, O'Neill, J, Carlson, P, Lamsam, J, Janzow, D, Eckert, D, et al
Gastroenterology. 2013;144(5):903-911.e3
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The relationship between gluten exposure and diarrhoea-predominant irritable bowel syndrome (IBS-D) is not well understood. Non-celiac IBS-D patients who are positive for HLA-DQ2/8 genes associated with CD can show symptom improvement on a gluten-free diet (GFD). The aim of this 4-week parallel randomized controlled clinical trial in HLA-DQ2/8 positive and negative patients with IBS-D was to assess the effects of a gluten-containing diet (GCD) compared to a GFD on bowel function, gut transit, small bowel (SB) and colonic barrier functions as measured by two-sugar excretion permeability test and mRNA expression of TJ proteins in mucosa of the small bowel (SB) and rectosigmoid (RS) derived by biopsy. Immune response to diets was also measured as cytokine production from peripheral blood mononuclear cells (PBMCs). Patient were recruited from the Mayo clinic’s database of IBS suffers, and invited to participate. Patients with diagnosed CD were excluded. Genotype analysis was performed for HLA-DQ2 and HLA-DQ8. 22 patients were placed on the GCD (11 HLA-DQ2/8–negative and 11 HLA-DQ2/8–positive) and 23 on the GFD (12 HLA-DQ2/8−negative and 11 HLA-DQ2/8–positive. All meals and snacks were ingested or prepared in the Mayo Clinic. Patients were advised to eat only the foods provided by the study dieticians. Gluten-free and gluten-containing meals were prepared using the same macronutrient content (20% protein, 30% fat, 50% carb). Compliance to the diet was assessed by direct questioning by the dietitians and reported to be excellent. All patients were ingesting gluten in their diet prior to starting the study. At 4-weeks, a statistically significant decrease in stool frequency of subjects on GFD compared to subjects on GCD (p=0.04) was seen. This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (p=0.019) There was no significant diet effect (GFD vs. GCD) on, daily stool form, ease of passage or gastric emptying. The GCD was associated with higher small bowel (SB) permeability (based on 0–2 hr levels of mannitol (p=0.028) and lactulose:mannitol ratio (P=0.0012)). SB permeability was greater in HLA-DQ2/8–positive than −negative patients (P=.018). No significant differences in colonic permeability were observed. Significant diet-associated changes in occludin expression in SB mucosa in the HLA-DQ2 or 8 positive group were seen (p=0.017). Expressions of tight junction proteins (zonulin (ZO-1), occludin, and claudin-1 mRNA) in colonic mucosa were significantly lower in GCD relative to GFD in the overall groups, particularly in subjects with HLA-DQ2 or 8 positive status. Cytokine response was higher (interleukin-10) in response to GCD than GFD (unrelated to HLA genotype). A limitation in the quantification of TJ protein expression is that it was solely based on PCR (mRNA expression). In future, other methods should be included to directly identify these proteins and their distribution. The inability to document alterations in colonic permeability using the 2-sugar excretion profile from 8 to 24 hours is a limitation. This may be due to lack of sensitivity of the lactulose and mannitol excretion test, for example, due to the metabolism of both sugars by colonic bacteria. Another limitation is that the mechanism for improvement in stool frequency on a GFD in the absence of changes in colonic transit was not elucidated by our studies. This study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed. The author concludes that this study provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS. The data also partially explains that the biological effects of gluten were associated with HLA-DQ2 or 8 genotype. The relationship of dietary factors, innate and adaptive immune responses and mucosal interactions in IBS-D deserve further study. Further clinical studies evaluating the effects of gluten withdrawal in patients with IBS-D are needed.
Abstract
BACKGROUND & AIMS Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). METHODS We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. RESULTS Subjects on the GCD had more bowel movements per day (P = .04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). CONCLUSIONS Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.govNCT01094041.
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The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.
Paterson, BM, Lammers, KM, Arrieta, MC, Fasano, A, Meddings, JB
Alimentary pharmacology & therapeutics. 2007;26(5):757-66
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In a healthy gut, intestinal epithelial cells, with their tight junctions, allow controlled passage of gluten and other fragments. When integrity of this system is compromised, as in celiac disease (CD), an inappropriate immune response to environmental antigens (i.e. gluten) develops. This is called hyper-intestinal permeability or 'leaky gut'. AT-1001 is a protein derived from a Gram-negative bacteria called Vibrio cholera. AT-1001 inhibits leaky gut and appears to have an impact on autoimmunity, making it a potential candidate for the treatment of CD. This double-blind, randomised placebo controlled study aims to determine the safety and tolerability of 12 mg doses of AT-1001 in CD subjects challenged with gluten. Intestinal permeability (IP) (measured urinary lactulose-to-mannitol) is used as a measure of drug efficacy. Male and female in-patients (n=20) aged 18-59y with diagnosed CD, on gluten-free diets for 6 months+ were, on days 1 and 3, treated with 12mg AT-1001 or placebo, followed by a sham gluten challenge, followed by the intestinal permeability measure. On day 2 the sham gluten was replaced by gluten. Puddings (containing sham or gluten) were served to all participants by kitchen staff in singe-blind fashion. For day 2 to day 1 IP change, there was a 70% increase in IP in the placebo group (P = 0.041) and no increase in the drug group, confirming the effects of gluten exposure on IP and the protective effects of AT-1001. Adverse events were mild (n=49) or moderate (n=3). Both groups experienced diarrhoea (an expected symptom in CD patients after exposure to gluten) but the AT-1001 treated volunteers reported less diarrhoea than placebo (P=0.017) suggesting a protective effect for AT-1001. This data demonstrate that 12 mg AT-1001 was generally safe, well tolerated and effectively mitigated gluten-induced GI adverse effects in coeliac patients when compared to placebo. Interferon (IFN)-γ (a marker of immune activity after acute dietary gluten) increased on day 3 in both the placebo group and AT-1001 group, but less so in the AT-1001 group though the difference was not statistically significant (likely due to small sample size). AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure. Larger studies are required to further elucidate the effects of AT-1001.
Abstract
BACKGROUND Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae. AIM: To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten. METHODS An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy. RESULTS Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-gamma levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018). CONCLUSIONS AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.
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Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449].
Dancey, CP, Attree, EA, Brown, KF
Nutrition journal. 2006;5:16
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Nucleotides are the building blocks of DNA and RNA. Dietary sources of nucleotides are found to varying degrees in many foods – lamb, liver, mushrooms (but not fruit and other vegetables) all are rich in nucleotides. Giving nucleotide supplements to infants has been shown to reduce the incidence and duration of diarrhoea, and animal studies show structural improvements in the intestines when nucleotide supplementation is given. The aim of this study was to test the hypothesis that nucleotide supplements would improve symptoms in people with Irritable Bowel Syndrome (IBS). Thirty-seven people with an IBS diagnosis took part in the study. Participants were asked to rate the severity of their IBS symptoms before and throughout the study period, and psychological measures (anxiety, depression, illness intrusiveness and general health) were also assessed. Participants were assigned to either placebo (56 days) followed by supplement (56 days) or the reverse. The supplement given was IntestAidIB which contained: nucleotides & RNA (concentrated extracts of Saccharomyces cerevisae), hydroxypropyl methylcellulose, FOS (fructo-oligosaccharides), Methionine, Glutamine, Inositol, Lysine, Pantothenic acid (Vitamin B5 as Calcium d-pantothenate), Sodium citrate, Riboflavin (Vitamin B2), Vanillin, Folic acid, and Biotin. The supplement improved the severity of all IBS symptoms, apart from diarrhoea, more than the placebo. Symptom improvement ranged from 4 - 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement and were statistically significant. The differences between groups for diarrhoea, bloating and flatulence were not significant. Although the improvements in symptoms were consistent, the effects were not strong, and the psychological measures showed no improvement. The authors concluded that dietary nucleotide supplementation improves some of the symptoms of IBS. Further studies need to replicate and extend these results, and clarify the mechanism by which improvements occur.
Abstract
BACKGROUND Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 - 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed.
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Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.
Bhutta, ZA, Bang, P, Karlsson, E, Hagenäs, L, Nizami, SQ, Söder, O
Archives of disease in childhood. 1999;80(5):438-42
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Persistent diarrhoea in childhood causes severe malnutrition, and morbidity in 15%+ cases. Treatment includes nutritional rehabilitation for weight gain and diarrheal recovery. This study evaluates nutritional recovery (defined as weight gain (> 5 g/kg/day) with a resolution of diarrhea by day 7 of treatment), intestinal permeability and insulin-like growth factor I (IGF-I) response in malnourished children with faltering growth (aged 6-36 months) with persistent diarrhoea ((>/= 14 days) and their relation to concomitant systemic infection(s) (as indicated by serum C reactive protein (CRP)). For a minimum of 7 days, 63 children were fed a previously validated dietary regimen (data not available) of rice–lentil (khitchri) and yogurt aimed at providing at least 100 kcal/kg/day by day 3, with ad libitum feeds thereafter. Children were nursed on a research ward throughout. 49 children were treatment successes. They had a significant increase in serum IGF-I and IGF-I% correlated with weight gain. 14 children did not meet the criteria for nutritional recovery. They had higher serum CRP concentrations and sepsis at admission. They had lower mean (SD) weight gain in spite of overall mean energy intake being comparable with treatment successes. This may indicate malabsoption. Admission CRP concentration and IGF-I were negatively correlated. CRP concentrations at admission and corresponding individual IGF-I values over the 7 days treatment were significantly correlated. Significantly raised CRP concentrations in children with a correspondingly low IGF-I response may indicate a continued inflammatory or infected state in these children. Small but opposing trends of urinary excretion of the oral lactulose dose were seen in both groups over the seven days of treatment, indicating worsening enteropathy (mucosal injury) among treatment failures. None of the permeability parameters correlated with IGF-I at baseline or recovery. The study confirms that a traditional rice–lentil (khitchri) and yogurt diet can be used successfully for enteral nutritional rehabilitation in malnourished children with persistent diarrhoea and leads to adequate weight gain; Serum IGF-I levels correlates closely with weight gain and reduction in stool output; recovery is delayed with sepsis and raised blood CRP concentrations at admission; IGF-I is depressed at admission in children with persistent diarrhoea. The data provide evidence that serum IGF-I response in recovering malnourished children with persistent diarrhoea may provide a sensitive measure of nutritional and diarrhoeal recovery. Further studies are needed to evaluate factors regulating the IGF-I response in such children, especially the effect of intercurrent infections. Arbitrary definition of treatment failure is a study limitation.
Abstract
OBJECTIVE Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (≥ 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.