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Effect of vaginal probiotics containing Lactobacillus casei rhamnosus (Lcr regenerans) on vaginal dysbiotic microbiota and pregnancy outcome, prospective, randomized study.
Petricevic, L, Rosicky, I, Kiss, H, Janjic, N, Kaufmann, U, Holzer, I, Farr, A
Scientific reports. 2023;13(1):7129
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Preterm delivery (PTD) of babies is thought in some women to be associated with the development of vaginal infections. An imbalance in the bacteria normally present in the vagina and especially a lack of Lactobacillus species can develop into a condition known as bacterial vaginosis (BV), which is a risk factor for PTD. The use of antibiotics is the standard treatment, however concerns on its effectiveness in preventing PTB have been raised. Antibiotics not only eradicate the abnormal bacteria, but also the Lactobacillus. This randomised control trial of 129 women with BV aimed to determine the effect of vaginally applied lactobacilli on the restoration of normal bacteria in the vagina and the rate of PTD. The results showed that women who had a complete lack of Lactobacillus, the vaginal application of Lactobacillus casei rhamnosus, BV was improved and gestational age at delivery and birthweight were both significantly increased, although PTD rate was not. It was concluded that vaginally applied Lactobacillus may be of some benefit to women with BV during pregnancy. This study could be used by healthcare professionals to understand the importance of vaginal microbiota during pregnancy. However, this was a study of very small numbers of women and larger studies are needed before vaginally applied microbiota can be definitively recommended.
Abstract
The intermediate bacterial microbiota is a heterogeneous group that varies in the severity of the dysbiosis, from minor deficiency to total absence of vaginal Lactobacillus spp. We treated women with this vaginal dysbiosis in the first trimester of pregnancy using a vaginally applied lactobacilli preparation to restore the normal microbiota in order to delay the preterm delivery rate. Pregnant women with intermediate microbiota of the vagina and a Nugent score of 4 were enrolled in two groups: intermediate vaginal microbiota and a Nugent score of 4 with lactobacilli (IMLN4) and intermediate vaginal microbiota and a Nugent score of 4 without lactobacilli (IM0N4), with and without vaginal lactobacilli at baseline, respectively. Half of the women in each group received the treatment. Among women without lactobacilli (the IM0N4 group), the Nugent sore decreased by 4 points only in the women who received treatment, and gestational age at delivery and neonatal birthweight were both significantly higher in the treated subgroup than in the untreated subgroup (p = 0.047 and p = 0.016, respectively). This small study found a trend toward a benefit of treatment with vaginal lactobacilli during pregnancy.
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Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.
Casselbrant, A, Wallenius, V, Elebring, E, Marschall, HU, Johansson, BR, Helander, HF, Fändriks, L
Nutrients. 2022;14(19)
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The small intestinal mucosa is a large organ which acts as an intestinal barrier. The jejunal mucosa is the largest part of the small intestinal mucosa, and its functions include digestion and absorption of food. Epithelium cells on the surface of the small intestine renew every few days. Therefore, this single-centre, randomised, unblinded, crossover study looked at how jejunal mucosal cells change after two weeks of an isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) in fifteen healthy people. The study also measured ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and mitochondria following the isocaloric HFD and HCD. Neither HFD nor HCD changes the mucosal surface enlargement factor. However, at the ultrastructural level, there was a significant surface enlargement in the bases of the villi after following HCD than HFD. In addition, HFD increased the number of mitochondrial cristae in the erythrocytes than HCD. The increased number of mitochondrial cristae in the erythrocytes was associated with the increased expression of HMGCS2. Healthcare professionals can use the results of this study to understand how short-term implementation of different diets affects jejunal mucosal morphology at the ultrastructural level. Further robust studies are required to evaluate the long-term effects of HFD and HCD in jejunal mucosa and how the morphological adaptations impact people with obesity.
Abstract
BACKGROUND AND AIMS The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. METHODS A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. RESULTS The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. CONCLUSION There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.
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Effect of physical fitness on colorectal tumor development in patients with familial adenomatous polyposis.
Nakamura, T, Ishikawa, H, Sakai, T, Ayabe, M, Wakabayashi, K, Mutoh, M, Matsuura, N
Medicine. 2019;98(38):e17076
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Familial adenomatous polyposis (FAP), is a rare genetic disease leading to a very high risk of developing colorectal cancer (CRC), with about half of all these patients developing cancer by the age of 40 years. Research has shown that exercise and physical fitness can reduce the risk of sporadic CRC. The aim of this cross-sectional study was to examine the relationship between physical fitness and CRC development in patients with FAP. 119 patients with FAP participated in the study and underwent an exercise stress test to determine physical fitness. The risk of CRC was significantly higher in those who were less physically fit. There was also a significant negative correlation between maximum polyp diameter and physical fitness. The authors conclude that physical fitness may play a role not only in the development of sporadic CRC, but also in cancer development in FAP. The mechanism by which physical fitness prevents the development of CRC and adenoma is largely unknown, but it is thought that improved insulin resistance and altered intestinal transit time may mediate the association.
Abstract
Although accumulated epidemiological evidence indicates that a good physical fitness level may prevent the development of sporadic colorectal cancer (CRC), few studies have examined the effect of physical fitness level on familial adenomatous polyposis (FAP). This cross-sectional study aimed to examine the relationship between physical fitness and CRC development in patients with FAP.A total of 119 patients (54 male; 65 female) with FAP, aged 17 to 73 years, underwent a step test to induce exercise stress. Predicted maximal oxygen uptake (VO2max) was calculated for each patient by using heart rate as an index of physical fitness. The association of VO2max with the presence or absence of CRC and polyp diameter was examined. Patients with FAP were divided into 3 categories according to their VO2max (high, medium, and low). The association between maximum polyp size and VO2max among the patients with FAP without a history of colectomy was examined.The risk of CRC was significantly higher in the low VO2max group than in the high VO2max group (odds ratio = 4.07; 95% confidence interval, 1.02-16.26). The maximum polyp diameter was significantly negatively correlated with the VO2max among the patients with FAP without a history of colectomy (r = -.44, P = .01). In the multiple linear regression analysis, maximum polyp diameter was independently correlated with VO2max.Our results suggest a preventive association between physical fitness and CRC development or colorectal adenoma growth exists in patients with FAP.
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Prolonged Collagen Peptide Supplementation and Resistance Exercise Training Affects Body Composition in Recreationally Active Men.
Kirmse, M, Oertzen-Hagemann, V, de Marées, M, Bloch, W, Platen, P
Nutrients. 2019;11(5)
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Currently little is known concerning collagen protein supplementation combined with a prolonged resistance exercising training (RET) programme. The aim of this study was to determine the effects of long-term collagen peptide supplementation and RET on body composition, strength and muscle fibre cross-sectional surface area (fCSA) in 57 recreationally active men. In this double-blind, placebo-controlled study, participants were randomly allocated to receive either collagen peptides or placebo for 12 weeks. Both groups trained three times a week. Strength testing, bioimedance analysis and muscle biopsies were taken at baseline and post-intervention. Most notably the collagen group experienced a significant increase in fat-free mass while body fat mass remained unchanged, compared to the placebo group. Both groups showed significant increases in strength tests and the fCSA increased significantly without differences. Based on these results, the authors conclude collagen protein supplementation have positive impact on body composition however suggest further study include connective tissue in addition to muscle tissue to better understand the mechanisms underlying these changes.
Abstract
We aimed to determine the effects of long-term collagen peptide (CP) supplementation and resistance exercise training (RET) on body composition, strength, and muscle fiber cross-sectional area (fCSA) in recreationally active men. Fifty-seven young men were randomly and double-blinded divided into a group receiving either collagen peptides (COL, 15 g/day) or a placebo (PLA). Strength testing, bioimpedance analysis, and muscle biopsies were used prior to and after an RET intervention. Food record protocols were performed during the RET intervention. The groups trained three times a week for 12 weeks. Baseline parameters showed no differences between groups, and the external training load and dietary food intake were also similar. COL showed a significant increase in fat-free mass (FFM) compared with the placebo group (p < 0.05). Body fat mass (BFM) was unchanged in COL, whereas a significant increase in BFM was observed in PLA. Both groups showed significant increases in all strength tests, with a trend for a slightly more pronounced effect in COL. The fCSA of type II muscle fibers increased significantly in both groups without differences between the two groups. We firstly demonstrated improved body composition in healthy, recreationally active men subsequent to prolonged CP supplementation in combination with RET. As the observed increase in FFM was not reflected in differences in fCSA hypertrophy between groups, we assume enhanced passive connective tissue adaptations in COL due to CP intake.
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Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection.
Palma, E, Recine, N, Domenici, L, Giorgini, M, Pierangeli, A, Panici, PB
BMC infectious diseases. 2018;18(1):13
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There is increasing interest in the role that the vaginal microbiome (the bacterial profile) plays in women’s health. Lactobacilli are the most dominant vaginal bacteria present in healthy women and it is known that when the bacteria get out of balance (a state called dysbiosis), disorders such as vaginosis and sexually transmitted diseases such as the Human Papilloma Virus (HPV) increase. This randomised pilot study aimed to investigate whether long-term use of Lactobacillus rhamnosus in women with dysbiosis and HPV-infection had an impact on treatment outcomes. 117 women with diagnosed vaginosis or vaginitis and HPV-infection were treated with standard antibiotic therapy and then randomly assigned to receive either 2-months or 6 months of vaginal Lactobacillus. At the median follow-up of 14 months post treatment, more than double the number of women in the 6-month probiotic treatment group received a negative HPV-pap smear, when compared to the 2-month treatment group. Randomised controlled trials are required to further this research, however Nutrition Practitioners working with women with vaginosis/vaginitis may want to consider the possible use of probiotics to support a healthy vaginal microbiome.
Abstract
BACKGROUND Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis. METHODS A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016. Women were randomized in two groups, standard treatment (metronidazole 500 mg twice a day for 7 days or fluconazole 150 mg orally once a day for 2 consecutive days) plus short-term (3 months) vaginal Lactobacillus implementation (group 1, short probiotics treatment protocol group, n = 60) versus the same standard treatment plus long-lasting (6 months) vaginal Lactobacillus rhamnosus BMX 54 administration (group 2, treatment group, n = 57). RESULTS After a median follow up of 14 months (range 9-30 months) the chance to solve HPV-related cytological anomalies was twice higher in probiotic long-term users (group 2) versus short probiotics implementation group (group 1) (79.4% vs 37.5%, p = 0.041). Moreover, a total HPV-clearance was shown in 11.6% of short schedule probiotics implementation patients compared to a percentage of 31.2% in vaginal Lactobacilli long term users (p = 0.044), assessed as negative HPV-DNA test documented at the end of the study period. CONCLUSIONS The consistent percentage of clearance of PAP-smear abnormalities and HPV-clearance obtained in long-term treatment group has been interestingly high and encouraging. Obviously, larger and randomized studies are warranted to confirm these encouraging results, but we believe that eubiosis re-establishment is the key to tackle effectively even HPV-infection. TRIAL REGISTRATION Retrospectively registered on PRS NCT03372395 (12/12/2017).
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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.
Salden, BN, Monserrat, V, Troost, FJ, Bruins, MJ, Edens, L, Bartholomé, R, Haenen, GR, Winkens, B, Koning, F, Masclee, AA
Alimentary pharmacology & therapeutics. 2015;42(3):273-85
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Gluten is high in proline, an amino acid that is not naturally broken down in the human gastrointestinal tract. In patients with coeliac disease, proline-rich gluten reaches the small intestine and triggers an abnormal immune response, causing inflammation and microvilli damage. The aim of this randomised study was to test the efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) on gluten degradation. AN-PEP belongs to a family of enzymes that has been previously known to break down proline in vitro. The study included 12 healthy volunteers aged 18-45 who were administered a low or high calorie meal containing 4.0g of gluten protein, with AN-PEP or placebo into the stomach. The findings of this study showed that AN-PEP significantly enhanced gluten digestion in the stomach before entering the duodenum of healthy volunteers. Based on this study, the authors conclude that AN-PEP is a promising option for degrading inadvertent dietary gluten consumption, and should be evaluated in target populations.
Abstract
BACKGROUND Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM: To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × min/mL; P = 0.001). CONCLUSIONS AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.
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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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Reintroduction of gluten following flour transamidation in adult celiac patients: a randomized, controlled clinical study.
Mazzarella, G, Salvati, VM, Iaquinto, G, Stefanile, R, Capobianco, F, Luongo, D, Bergamo, P, Maurano, F, Giardullo, N, Malamisura, B, et al
Clinical & developmental immunology. 2012;2012:329150
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A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying new strategies. Chemically altering the protein in wheat flour (transamidation of gliadin) reduces the reaction experienced in vitro in intestinal cells of CD patients. This randomized single blinded, controlled 90-day trial in 47 CD patients examines the safety of transamidated wheat flour compared to control. 35 patients received 50g a day of transamidated flour bread and 12 received 3.7g of non-transamidated flour bread. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse whereas intestinal permeability was mainly altered in the control group. On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no change to the autoantibody found in CD (Ttg) and other markers of CD. This study demonstrated that a protracted intake of gluten from chemically treated wheat flour was associated with a reduced number of relapses in challenged patients. Nevertheless, the enzyme reaction did not eradicate gluten activity in all CD patients examined. Whether an upgrade of the transamidation reaction might be instrumental in blocking other immune components involved in the mucosal lesion is under investigation.
Abstract
A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.
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Dose dependent effects of protracted ingestion of small amounts of gliadin in coeliac disease children: a clinical and jejunal morphometric study.
Catassi, C, Rossini, M, Rätsch, IM, Bearzi, I, Santinelli, A, Castagnani, R, Pisani, E, Coppa, GV, Giorgi, PL
Gut. 1993;34(11):1515-9
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Coeliac disease (CD) is an intestinal reaction that is caused by the ingestion of gluten. While this is well established, the relationship between the quantity ingested and the severity of adverse effects, namely for small amounts of gluten, is still unclear. The aim of this study was to assess the effects of chronic ingestion of small amounts of gluten in children with CD. 20 children who had been on a long-term gluten-free diet were given a daily dose of either 100 mg or 500 mg of gliadin for four weeks. Effects were measured through an intestinal biopsy, antibody test and sugar intestinal permeability test. The findings of this study showed that in children with CD, chronic ingestion of gluten causes dose-dependent damage to intestinal mucosa and lymphocyte infiltration.
Abstract
This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.