Bo Tjellström

Gut Microflora Associated Characteristics in Children with Celiac Disease

OBJECTIVES:The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls.METHODS:The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas–liquid chromatography of short chain fatty acids (SCFAs) in fecal samples.RESULTS:There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups.CONCLUSIONS:This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.

Effect of exclusive enteral nutrition on gut microflora function in children with Crohn's disease

Abstract Objective. Exclusive enteral nutrition (EEN) is a first-line treatment in children with active Crohns disease (CD) but is seldom used in adults with active disease. The mode of action of EEN in suppressing mucosal inflammation is not fully understood, but modulation of intestinal microflora activity is one possible explanation. The aim of this study was to investigate the effect of 6-week EEN in children with active CD, with special reference to intestinal microflora function. Materials and methods. Fecal samples from 18 children (11 boys, 7 girls; median age 13.5 years) with active CD (13 children with small bowel/colonic and 5 with perianal disease) were analyzed for short chain fatty acid (SCFA) pattern as marker of gut microflora function. The children were studied before and after EEN treatment. Results from 12 healthy teenagers were used for comparison. Results. Eleven (79%) of the children with small bowel/colonic CD responded clinically positively to EEN treatment showing decreased levels of pro-inflammatory acetic acid as well as increased concentrations of anti-inflammatory butyric acids and also of valeric acids, similar to the levels in healthy age-matched children. In children with active perianal CD, however, EEN had no positive effect on clinical status or inflammatory parameters. Conclusions. The authors present new data supporting the hypothesis that the well-documented anti-inflammatory effect of EEN in children with active small bowel/colonic CD is brought about by modulation of gut microflora activity, resulting in an anti-inflammatory SCFA pattern. By contrast, none of the children with perianal disease showed clinical or biochemical improvement after EEN treatment.

Gut microflora associated characteristics in first-degree relatives of children with celiac disease

Objective. In celiac disease (CD), enteropathy of the small bowel results from a T-cell-mediated reaction to gluten in the diet. In addition to gluten, other environmental and genetic factors participate in the disease pathogenesis. We have recently reported the finding of a significantly different short-chain fatty acid (SCFA) profile in fecal samples from children with CD compared to healthy controls reflecting an aberrant gut microflora. The aim of the present study was to make a functional evaluation of the gut microflora status in non-celiac 1st degree relatives of children with CD. Material and methods. Fecal samples from 76 symptom-free, non-celiac, 1st degree CD relatives and from 91 aged-matched healthy controls were analyzed for fecal tryptic activity (FTA) and a number of SCFAs. Results. There was a significantly lower level of acetic acid and total SCFAs as well as a significantly increased level of i-butyric acid and FTA in relatives compared to healthy controls. Conclusions. The FTA and the SCFA profiles in fecal samples from 1st degree relatives of children with CD are different from those of healthy individuals. The implication of this observation provides insight into the pathogenesis of CD and opens up the possibility of future new diagnostic, therapeutic and prophylactic strategies.

Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year’s gluten-free diet

Objective Recent work indicates that the gut microflora is altered in patients with coeliac disease (CD). Faecal short-chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported a high SCFA output in children with symptomatic and asymptomatic CD at presentation, as well as in CD children on a gluten-free diet (GFD) for less than 1 year, indicating deviant gut microfloral function. In this report, we focus on faecal SCFA production in coeliacs on GFD for more than 1 year. Materials and methods Faecal samples were collected from 53 children with CD at presentation, 74 coeliac children on GFD for less than 1 year, and 25 individuals diagnosed with CD in childhood and on GFD for more than 1 year. The control group comprised 54 healthy children (HC). The faecal samples were analysed to show the SCFA pattern taken as a marker of gut microflora function. We applied a new fermentation index, reflecting the inflammatory activity of the SCFAs (amount of acetic acid minus propionic acid and n-butyric acid, together divided by the total amount of SCFAs). Results In coeliacs on GFD for more than 1 year, the individual SCFAs, total SCFA, and fermentation index did not differ significantly from the findings in controls. In contrast, the faecal SCFA level was clearly higher in coeliacs treated with GFD for less than 1 year compared to those more than 1 year. Conclusions This is the first study on SCFA patterns in faecal samples from individuals with CD on GFD for more than 1 year. Our study indicates that the disturbed gut microflora function in children with CD at presentation and after less than 1 year of GFD, previously demonstrated by us, is normalised on GFD for more than 1 year.

The effects of oats on the function of gut microflora in children with coeliac disease

Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat‐free oats can safely be included in a gluten‐free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs.

Intranasal versus intravenous administration of midazolam to children undergoing small bowel biopsy

Sixty‐three children under the age of 9 years were randomized to receive intravenous (group A, n= 33) or intranasal (group B, n= 30) midazolam as sedation for small bowel biopsy. Mean doses of midazolam given to produce adequate sedation were 0.31 mg (kg body weight)−1 in group A and 0.34 mg (kg body weight)−1 in group B (NS). Four children in group A and 10 children in group B required additional doses to maintain adequate sedation throughout the biopsy procedure (p <0.05). There was no significant difference between the groups regarding the median procedure time (7 min in group A, 8.5 min in group B) or median fluoroscopy time (5 s in group A, 4 s in group B). All children in group B showed signs of discomfort from the nose when given midazolam intranasally. In conclusion, this study indicates that intravenous administration of midazolam is preferable to the intranasal route.

A Role for Bacteria in Celiac Disease

In their excellent review of the gut microbiota in celiac disease (CD), Marasco et al. [1] evaluate the current evidence for its role in the pathogenesis of the disease and in the effect of the gluten-free diet (GFD) treatment. They present recent studies on the fecal microflora in CD indicating a dysbiosis. The function of the gut flora is mirrored by various microflora-associated characteristics, e.g., the fecal content of bacterial metabolites, such as short-chain fatty acids (SCFAs) [2]. Here, our group was the first to report on the deviant fecal SCFA pattern in CD [3], which later on has been confirmed by others (for lit. ref., see [1]). It has been discussed whether the deviant gut microflora and its functions are causative factors in CD or merely consequences of the disease [4]. The review by Marasco et al. also deals with this issue. The authors conclude that the dysbiosis is reduced, but not restored, by GFD. This may, however, very well be a matter of time. Judging from our studies of the effect of GFD on the fecal SCFA pattern, a CD patient still displayed a deviant gut microflora function after \1 year of GFD, which was normalized only after GFD for more than 1 year [5]. This indicates that the celiac dysbiosis is indeed a long-lasting consequence of the susceptibility to gluten and that the disturbed microflora function, as evidenced by associated fecal metabolites, might be an epiphenomenon rather than a cause of disease.

John Walker-Smith: the father of European paediatric gastroenterology

The rapid development of paediatrics during the latter half of the 20th century led to organ‐specific subspecialities being established. One of these was paediatric gastroenterology, which was pion ...

Oral immunoglobulin treatment improved intestinal permeability in children with active Crohn's disease

Crohns disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohns disease.

Exclusive Enteral Nutrition Does Not Normalize Gut Microflora Function in Pediatric Perianal Crohn Disease

T o the Editor: In their excellent overview, de Zoeten et al (1) present detailed and practical guidelines for the diagnosis and treatment of perianal Crohn disease (CD) in children. In the section on enteral therapy (page 406), they refer to a report of successful treatment with enteral nutrition in 3 children with perianal CD (2). Exclusive enteral nutrition (EEN) is a wellestablished and effective treatment in pediatric CD (3). Although the mode of action of EEN is not fully understood, modulation of the gut microflora activity in a less inflammatory direction has been proposed to be a probable explanation (4–6). Further evidence of a gut microflora–mediated anti-inflammatory effect of EEN in children with active CD was recently presented by us, analyzing the fecal short-chain fatty acid (SCFA) profile, which reflects the gut microfloral function (7). We showed that 6 weeks’ EEN normalized the initially proinflammatory SCFA pattern, resulting in clinical remission. Interestingly, only children with active small bowel and/or colonic CD had a positive effect of the treatment. In children with active perianal CD, EEN had no positive effect on clinical status, inflammatory parameters, or SCFA pattern. Thus, our findings question the use of EEN as the treatment for perianal CD and illustrate the need for further research on the complex interactions between genetics, dietary nutrients, gut microflora metabolites, and intestinal inflammation in individuals with CD (6,8).