Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans.

BACKGROUND: We have shown that a galactooligosaccharide prebiotic administration (HOST-G904) initially increased intestinal gas production and this increase declined back to baseline after 2 week administration. Our aim was to determine the mechanism of microbiota adaptation; i.e., to determine whether the net reduction is due to decreased overall production or increased gas consumption. METHODS: In 10 healthy subjects, intestinal gas production and intraluminal disposal was measured before, at the beginning and after 2 week of HOST-G904 prebiotic administration. Anal gas was collected for 4 hour after a probe meal. Paired studies were performed without and with high-rate infusion of exogenous gas (24 mL/min) into the jejunum to wash-out the endogenous gas produced by bacterial fermentation. The exogenous gas infused was labeled (5% SF6 ) to calculate the proportion of endogenous gas evacuated. KEY RESULTS: The volume of intestinal gas produced i.e., endogenous gas washed-out, increased by 37% at the beginning of HOST-G904 administration (P=.049 vs preadministration) and decreased down to preadministration level after 2 week administration (P=.030 vs early administration). The proportion of gas eliminated from the lumen before reaching the anus tended to increase after 2-week administration (87±3% vs 78±5% preadministration; P=.098). CONCLUSIONS & INFERENCES: Adaptation to regular consumption of HOST-G904 prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways, with a non-significant increase in gas-consuming activity. Hence, regular consumption of HOST-G904 regulates intestinal gas metabolism: less gas is produced and a somewhat larger proportion of it is consumed.

The Mexican consensus on probiotics in gastroenterology. / Consenso mexicano sobre probióticos en gastroenterología.

INTRODUCTION: Probiotics are frequently prescribed in clinical practice. Their efficacy in treating gastrointestinal disorders is supported by a significant number of clinical trials. However, the correct prescription of these agents is hampered due to a lack of knowledge of the scientific evidence and to the different presentations and microbial compositions of the probiotics that are currently available. AIM: To provide the clinician with a consensus review of probiotics and recommendations for their use in gastroenterology. MATERIALS AND METHODS: Controlled clinical trials, meta-analyses, and systematic reviews published up to 2015 were selected, using the MESH terms: probiotics, gastrointestinal diseases, humans, adults, AND children. The Delphi method was employed. Eighteen gastroenterologists treating adult patients and 14 pediatric gastroenterologists formulated statements that were voted on until agreement>70% was reached. The level of evidence based on the GRADE system was evaluated for each statement. RESULTS AND CONCLUSIONS: Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis and pouchitis, and the treatment of covert and overt hepatic encephalopathy.

Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study.

BACKGROUND: Prebiotics have been shown to reduce abdominal symptoms in patients with functional gut disorders, despite that they are fermented by colonic bacteria and may induce gas-related symptoms. AIM: To investigate changes in the metabolic activity of gut microbiota induced by a recognised prebiotic. METHODS: Healthy subjects (n = 20) were given a prebiotic (2.8 g/day HOST-G904, HOST Therabiomics, Jersey, Channel Islands) for 3 weeks. During 3-day periods immediately before, at the beginning and at the end of the administration subjects were put on a standard diet (low fibre diet supplemented with one portion of high fibre foods) and the following outcomes were measured: (i) number of daytime gas evacuations for 2 days by means of an event marker; (ii) volume of gas evacuated via a rectal tube during 4 h after a test meal; and (iii) microbiota composition by faecal Illumina MiSeq sequencing. RESULTS: At the beginning of administration, HOST-G904 significantly increased the number of daily anal gas evacuations (18 ± 2 vs. 12 ± 1 pre-administration; P < 0.001) and the volume of gas evacuated after the test meal (236 ± 23 mL vs. 160 ± 17 mL pre-administration; P = 0.006). However, after 3 weeks of administration, these effects diminished (11 ± 2 daily evacuations, 169 ± 23 mL gas evacuation). At day 21, relative abundance of butyrate producers (Lachnospiraceae) correlated inversely with the volume of gas evacuated (r = -0.52; P = 0.02). CONCLUSION: The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239.

Effect of inulin and fructo-oligosaccharide on the prevention of acute radiation enteritis in patients with gynecological cancer and impact on quality-of-life: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: The pathogenesis of enteritis after abdominal radiotherapy (RT) is unknown, although changes in fecal microbiota may be involved. Prebiotics stimulate the proliferation of Lactobacillus spp and Bifidobacterium spp, and this may have positive effects on the intestinal mucosa during abdominal RT. SUBJECTS/METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with gynecological cancer who received abdominal RT after surgery. Patients were randomized to receive prebiotics or placebo. The prebiotic group received a mixture of fiber (50 inulin and 50% fructo-oligosaccharide), and the placebo group received 6 g of maltodextrin twice daily from 1 week before to 3 weeks after RT. The number of bowel movements and stool consistency was recorded daily. Diarrhea was evaluated according to the Common Toxicity Criteria of the National Cancer Institute. Stool consistency was assessed using the 7-point Bristol scale. Patients' quality-of-life was evaluated at baseline and at completion of RT using the EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer quality-of-life Questionnaire C30) test. RESULTS: Thirty-eight women with a mean age of 60.3±11.8 years participated in the study. Both groups (prebiotic (n=20) and placebo (n=18)) were comparable in their baseline characteristics. The number of bowel movements per month increased in both groups during RT. The number of bowel movements per day increased in both groups. The number of days with watery stool (Bristol score 7) was lower in the prebiotic group (3.3±4.4 to 2.2±1.6) than in the placebo group (P=0.08). With respect to quality-of-life, the symptoms with the highest score in the placebo group were insomnia at baseline and diarrhea toward the end of the treatment. In the prebiotic group, insomnia was the symptom with the highest score at both assessments, although the differences were not statistically significant. CONCLUSIONS: Prebiotics can improve the consistency of stools in gynecologic cancer patients on RT. This finding could have important implications in the quality-of-life of these patients during treatment.

Accumulative effect of food residues on intestinal gas production.

BACKGROUND: As mean transit time in the colon is longer than the interval between meals, several consecutive meal loads accumulate, and contribute to colonic biomass. Our aim was to determine the summation effect of fermentable food residues on intestinal gas production. METHODS: In eight healthy subjects, the volume of endogenous intestinal gas produced in the intestine over a 4-h period was measured by means of a wash-out technique, using an exogenous gas infusion into the jejunum (24 mL/min) and collection of the effluent via a rectal Foley catheter. The exogenous gas infused was labeled (5% SF6 ) to calculate the proportion of endogenous intestinal gas evacuated. In each subject, four experiments were performed ≥1 week apart combining a 1-day high- or low-flatulogenic diet with a test meal or fast. KEY RESULTS: Basal conditions: on the low-flatulogenic diet, intestinal gas production during fasting over the 4-h study period was 609 ± 63 mL. Effect of diet: during fasting, intestinal gas production on the high-flatulogenic diet was 370 ± 146 mL greater than on the low-flatulogenic diet (p = 0.040). Effect of test meal: on the low-flatulogenic diet, intestinal gas production after the test meal was 681 ± 114 mL greater than during fasting (p = 0.001); a similar effect was observed on the high-flatulogenic diet (599 ± 174 mL more intestinal gas production after the test meal than during fasting; p = 0.021). CONCLUSIONS & INFERENCES: Our data demonstrate temporal summation effects of food residues on intestinal gas production. Hence, intestinal gas production depends on pre-existing and on recent colonic loads of fermentable foodstuffs.

Safety of probiotics and synbiotics in children under 18 years of age.

This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.

The administration of probiotics and synbiotics in immune compromised adults: is it safe?

This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.

Effect of a low-flatulogenic diet in patients with flatulence and functional digestive symptoms.

BACKGROUND: Diets rich in fermentable residues increase intestinal gas production. Our aim was to demonstrate the potential effects of diet on gas-related symptoms. METHODS: The effect of a low-flatulogenic test diet (restricted to foodstuffs low in fermentable residues; n = 15) was compared to that of a balanced control diet (Mediterranean type; n = 15) in 30 patients complaining of flatulence and other abdominal symptoms using a randomized parallel design. The following outcomes were measured daily: number of anal gas evacuations by an event marker, severity of gas-related symptoms by 0-10 scales, and sensation of digestive comfort by a -5 (unpleasant) to +5 (pleasant) scale. Measurements were taken pretreatment for 3 days on their habitual diet and for 7 days during the treatment phase. KEY RESULTS: No pretreatment differences were detected between patients allocated to the control or test diets. The test diet significantly reduced the number of gas evacuations (by 54 ± 10%; p = 0.002 vs basal diet) whereas the control diet had a lesser effect (reduction by 28 ± 9%; p = 0.059 vs basal diet; p = 0.089 vs test diet). Compared to the control diet, the test diet significantly reduced flatulence (by 48 ± 7% vs 27 ± 8%, respectively; p = 0.018), abdominal distension (by 48 ± 4% vs 22 ± 12%, respectively; p = 0.038), and enhanced digestive well-being (by 149 ± 18% vs 58 ± 22%, respectively; p = 0.006). CONCLUSIONS & INFERENCES: In patients with gas-related symptoms, a low-flatulogenic diet produces immediate beneficial effects with digestive, cognitive, and emotive dimensions. The number of gas evacuations is an objective biological marker of response to dietary treatment.

Probiotic and synbiotic safety in infants under two years of age.

In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.

Colonisation by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis.

BACKGROUND: Although incrimination of the intestinal microbiota in the pathogenesis of IBD is widely accepted, few data are available about the role of specific bacteria. Potentially, Faecalibacterium prausnitzii, bacteria with anti-inflammatory properties, might be deficient in ulcerative colitis (UC). AIM: To quantify F. prausnitzii in the faecal microbiota of UC patients in remission and determine its relationship with relapse. METHODS: A cross-sectional study included 116 UC patients in remission, 29 first-degree relatives and 31 healthy controls. A subset of eighteen patients, recruited during the first month of remission, underwent a 1-year follow-up. Total bacteria and F. prausnitzii were measured by quantitative Real Time PCR (qPCR, copies/g). Calprotectin was determined as inflammatory index (µg/g). RESULTS: We found that F. prausnitzii was reduced in patients (median, IQR: 1.4 × 108 , 5.1 × 107-4.5 × 108) and relatives (1.7 × 108, 9.3 × 107-5.1 × 108) vs. controls (6.5 × 108, 3.7 × 108-1.6 × 109, P < 0.0001). Moreover, low counts of F. prausnitzii were associated with less than 12 months of remission (8.0 × 107, 2.0 × 107-3.5 × 108 vs. 2.1 × 108, 1.0 × 108-7.9 × 108, P < 0.001) and more than 1 relapse/year (8.0 × 107, 3.2 × 107-3.8 × 108 vs. 1.9 × 108, 6.8 × 107-6.0 × 108, P < 0.01). When patients were followed up, F. prausnitzii increased steadily until reaching similar levels to those of controls if remission persisted (2.9 × 108, 9.3 × 106-1.2 × 109; calprotectin: 76, 19-212), whereas it remained low if patients relapsed (2.2 × 108, 1.4 × 106-3.3 × 108; calprotectin: 1760, 844-3662 P < 0.05 vs. controls). CONCLUSIONS: Defective gut colonisation by F. prausnitzii occurred in UC patients during remission and in their unaffected relatives. The recovery of the F. prausnitzii population after relapse is associated with maintenance of clinical remission.

Gut microbiota and gastrointestinal health: current concepts and future directions.

BACKGROUND: The microbial community of the human gut - the enteric microbiota - plays a critical role in functions that sustain health and is a positive asset in host defenses. In recent years, our understanding of this so-called human 'super organism' has advanced, following characterization of fecal metagenomes which identified three core bacterial enterotypes, and based on basic and clinical research into the impact and consequences of microbiota biodiversity and change on gastrointestinal disorders and diseases. PURPOSE: This article considers current knowledge and future perspectives on the make-up and function of human gut microbiota, with a particular focus on altered microbiota and gastrointestinal disorders, nutritional influences on the gut microbiota, and the consequences for gastrointestinal health, as well as improved understanding of gut-microbiota-brain communication.

Effect of a mixture of inulin and fructo-oligosaccharide on Lactobacillus and Bifidobacterium intestinal microbiota of patients receiving radiotherapy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: The pathogenesis of enteritis after abdominal radiotherapy is unknown, although changes in faecal microbiota may be involved. In several studies, Lactobacillus and Bifidobacterium have proven beneficial for the host. Prebiotics stimulate the proliferation of Lactobacillus and Bifidobacterium, and this may have positive effects on the intestinal mucosa during abdominal radiotherapy. METHODS: We performed a randomised double-blind, placebo-controlled trial including 31 patients with gynaecological cancer who received radiotherapy (29 sessions, 52.2 Gy) after surgery. Patients were randomised to two groups: prebiotic and placebo. The first group received a mixture of fibre (50% inulin and 50% fructo-oligosaccharide) and the second received 6 g of maltodextrin twice daily from one week before to three weeks after radiotherapy. Lactobacillus and Bifidobacterium counts were determined in faeces samples (day -7 before radiotherapy, day 15 of radiotherapy, at the end of treatment, and three weeks after radiotherapy) by culture in selective media and fluorescent in situ hybridization (FISH) using genus-specific probes. Bacterial counts by FISH were significantly higher than by culture method. RESULTS: There were no differences in baseline microbiota between groups. At the end of radiotherapy, we observed a statistically significant decrease in Lactobacillus and Bifidobacterium counts in both groups. By cultural analysis, we observed higher numbers of Lactobacillus and Bifidobacterium three weeks after radiotherapy in the prebiotic group (5.6 vs. 6.3, p = 0.04 and 5.5 vs. 6 log cfu/g, p = 0.03). CONCLUSIONS: Abdominal radiotherapy negatively affects Lactobacillus and Bifidobacterium counts. The prebiotic mixture of inulin and fructoligosaccharide can improve the recovery of both genera after radiotherapy. Registered under ClinicalTrials.gov Identifier no. NCT01549782.

Cutoff values of the Inflammatory Bowel Disease Questionnaire to predict a normal health related quality of life.

UNLABELLED: One of the objectives in the treatment of the inflammatory bowel disease (IBD) is improving the patient's quality of life. However, we do not dispose of validated criteria to determine the questionnaire's scoring threshold that has to be reached in order to be able to assert that the patients' quality of life has normalized. OBJECTIVE: To determine the normality punctuation cutoff in the IBD specific quality of life questionnaire IBDQ-36. METHOD: Cross-sectional study in a random sample of IBD patients, who have completed the questionnaires IBDQ-36 and EuroQol-5D. The IBDQ-36 normality was calculated according to its equivalence with the EuroQol-5D tariff ≥ 0.90, which corresponds to the 95% CI of the average obtained in a Spanish general population. RESULTS: 218 patients were included. According to the EuroQol-5D tariff, 70 patients were considered to have a normal quality of life and 148 a quality of life poorer than the general population. The IBDQ-36 scoring was significantly higher in the normal quality of life group (222.9 ± 22.8 vs. 171.4 ± 44.8 in the bad quality of life group, p<0.001). According to the linear regression between IBDQ-36 and EuroQol-5D, the cutoff point is 209, with a sensitivity and specificity to predict normality of 0.74 and 0.71 respectively. CONCLUSIONS: Scores of the IBDQ-36 equal or superior to 209 suggest quality of life comparable to that perceived by the general population. This study allowed to set a threshold of normality in the management of the inflammatory bowel diseases.

Influence of colectomy on hydrogen excretion in breath.

INTRODUCTION: Hydrogen breath test is the most commonly used method to analyze carbohydrate absorption and diagnose carbohydrate malabsorption. The result of the H(2) breath test is influenced by different factors, which are mostly related to quantitative or qualitative aspects of colonic flora. A scarcely studied variable is the effect of colonic anatomical integrity on H(2) excretion in breath. PURPOSE: The present study aims to determine whether loss of colonic integrity reduces H(2) excretion capacity after an oral load of an unabsorbable carbohydrate. METHODS: An observational study was conducted in three patient groups: controls with preserved colon, patients with partial colectomy, and patients with complete colectomy and ileostomy. H(2) concentration in breath was measured by gas chromatography every 10 min for 3 h after oral lactulose administration. RESULTS: Twenty-two patients with partial colectomy, 18 controls with preserved colon, and seven patients with ileostomy were included. H(2) excretion after lactulose did not differ between patients with partial colectomy and controls (basal excretion = 8.5 vs 4 ppm; delta increase = 50.0 vs 47.5 ppm; area under the curve = 4,480.0 vs 4,710.5 ppm/min). In contrast, H(2) excretion was significantly lower in the ileostomy group. CONCLUSIONS: Partial colectomy does not influence the capacity for H(2) excretion after oral unabsorbable carbohydrate administration.

Consensus statements from the Workshop "Probiotics and Health: Scientific evidence".

This report shows the level of scientific consensus on definition, characteristics and health benefits of probiotics. The content of the report has derived from the scientific meeting: Workshop on Probiotics and Health. Scientific evidence, that congregated several Spanish experts, including gastroenterologists, microbiologists, nutritionists, immunologists and food technologists, among others, who have agreed with the statements shown in this document. Each statement has been sustained with the most relevant scientific aspects that were discussed during the Workshop and the following evaluation of the report by all experts who approved and signed it.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Faecal DNA and calprotectin as biomarkers of acute intestinal toxicity in patients undergoing pelvic radiotherapy.

BACKGROUND: Acute intestinal toxicity is a frequent complication that may lead to interruption of treatment in patients undergoing pelvic radiotherapy. Reliable, non-invasive biological markers to evidence their severity are not yet available. AIM: To test faecal DNA and calprotectin as potential biomarkers of intestinal toxicity caused by pelvic radiotherapy. METHODS: Patients were categorized according to the location of the cancer as nonrectal (n = 25) and rectal (n = 27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy) and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA. Intestinal toxicity was scored according to the Common Toxicity Criteria. RESULTS: In the nonrectal group, acute diarrhoea toxicity was present in 80% of patients, faecal DNA increased 10-fold during radiotherapy (1.5 x 10(3) copies/mg dry weight, 9.5 x 10(2)-8.8 x 10(3) at w0, median and interquartile range vs. 1.3 x 10(4), 1.9 x 10(3)-3.9 x 10(4) at w5, P < 0.01), but was not recovered at w7 (3.4 x 10(3), 1.5 x 10(3)-4.1 x 10(4)) and calprotectin doubled during treatment at w3 and w5. No significant changes in faecal markers were found in the rectal group. CONCLUSION: Faecal excretion of human DNA and calprotectin increased during pelvic radiotherapy treatment, and may be a good objective biomarker of intestinal damage in nonrectal cancer patients.

Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin.

BACKGROUND: Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. OBJECTIVE: To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. DESIGN: Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g/day) and randomly allocated to receive either oligofructose-enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. RESULTS: Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 +/- 659 microg/g; day 7: 1033 +/- 393 microg/g, P < 0.05) but not in the placebo group (day 0: 5834 +/- 1563 microg/g; day 7: 4084 +/- 1395 microg/g, n.s.). Changes in faecal concentration of human DNA were not significant. CONCLUSION: In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.

Selective inhibition of phosphodiesterase-4 ameliorates chronic colitis and prevents intestinal fibrosis.

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.