Dysbiosis plays a major role in the etiology of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is a new promising option for IBD treatment. We aimed to assess the effectiveness of a two-week FMT course in children with IBD. Ten patients, 10-17 years of age with moderate to severe IBD received a course of eight doses of freshly prepared FMT via a naso-duodenal tube or gastroscopy. All of the patients had pancolitis. There were eight cases of ulcerative colitis (UC) and two of Crohn's disease (CD). Disease activity was evaluated using the Pediatric UC Activity Index (PUCAI) and Pediatric CD Activity Index (PCDAI) for UC and CD, respectively, CRP, and fecal calprotectin on the day before the first infusion and then on the day before the next course of FMT. Clinical response, defined as a decrease of 15 points in either index, was observed in 9/10 patients (seven UC and two CD). Clinical remission, defined as a PCDAI score ≤ 10 and PUCAI score < 10 measured at the same time point, was observed in 3/8 UC patients and 2/2 CD patients. Side effects observed were self-limiting and benign. We conclude that a short, intensive course of FMT has a beneficial effect on UC and CD colitis. FMT was well-tolerated and safe. Nonetheless, an optimal protocol of FMT administration is crucial for treatment efficacy.
Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.
New Findings
What is the central question of this study?‘Leaky gut’ has been found in intestinal and extra‐intestinal diseases. However, functional evaluation of intestinal permeability is not widely used as a diagnostic marker, possibly owing to significant limitations of currently used permeability assays. There is an unmet need for development of a new, non‐invasive test to assess intestinal function.
What is the main finding and its importance?We show that an increased blood‐to‐stool ratio of the concentration of gut bacteria‐produced short‐chain fatty acids may be used as a marker of gut permeability. Our findings lay the groundwork for establishing a new, non‐invasive, risk‐free diagnostic tool in diseases associated with intestinal barrier malfunction, such as inflammatory bowel disease.
Abstract
Intestinal diseases, such as inflammatory bowel disease (IBD), are characterized by an impaired gut–blood barrier commonly referred to as ‘leaky gut’. Therefore, functional evaluation of the gut–blood barrier is a promising diagnostic marker. We hypothesized that short‐chain fatty acids (SCFAs) produced by gut bacteria might serve as a marker in IBD. Animal experiments were performed on male Sprague–Dawley rats with acetic acid‐induced colitis and in sham control animals. The gut–blood barrier permeability was determined by assessing the ratios of the following: (i) portal blood concentration of SCFAs (Cp) to faecal concentration of SCFAs (Cf); (ii) systemic blood concentration of SCFAs (Cs) to faecal concentration of SCFAs (Cf); and (iii) Cp and Cs of fluorescein isothiocyanate (FITC)–dextran administered into the colon. As a clinical study, we evaluated Cs, Cf and the Cs/Cf ratio of SCFAs in six paediatric patients with IBD, assessed as mild/moderate/severe by the Paediatric Ulcerative Colitis Activity Index (PUCAI) and the Paediatric Crohn's Disease Activity Index (PCDAI) at the time of sample collection, and nine age‐matched healthy control subjects. Rats with histologically confirmed IBD had significantly increased ratios of Cp/Cf and Cs/Cf for SCFAs. This was positively correlated with the plasma FITC–dextran concentration. Likewise, IBD patients showed a significantly higher Cs/Cf ratio for SCFAs, including acetic, valeric, isocaproic, caproic and propionic acids, in comparison to control subjects. In conclusion, in the rats and in paediatric patients with IBD we found an increased blood‐to‐stool ratio of SCFAs, suggesting an increased gut‐to‐blood penetration of SCFAs. These findings pave the way for a new, non‐invasive diagnostic tool in IBD and other diseases accompanied by intestinal barrier malfunction.
Background/AimsThree-dimensional high-resolution anorectal manometry (3D-HRAM) is a precise tool to assess the function of the anorectum. Our aim is to evaluate children diagnosed with non-retentive fecal incontinence (NRFI) using 3D-HRAM.
MethodsIn all children diagnosed with NRFI, manometric parameters and 3-dimensional reconstructions of the anal canal subdivided into 8 segments were recorded. All data were compared to raw data that were obtained from asymptomatic children, collected in our laboratory and published previously (C group).
ResultsForty children (31 male; median age, 8 years; range, 5-17) were prospectively included in the study. Comparison of the NRFI group and C group revealed lower values of mean resting pressure (74.4 mmHg vs 89.2 mmHg, P < 0.001) and maximum squeeze pressure (182 mmHg vs 208.5 mmHg, P = 0.018) in the NRFI group. In the NRFI group, the thresholds of sensation, urge and discomfort (40 cm 3 , 70 cm 3 , and 140 cm 3 , respectively) were significantly higher than those in the C group (20 cm 3 , 30 cm 3 , and 85 cm 3 , respectively; P < 0.001). In the NRFI group, 62.5% presented a mean resting pressure above the fifth percentile, and 82.5% of patients presented a maximum squeeze pressure above the fifth percentile. The comparisons between segments obtained from these patients and those obtained from the C group revealed several segments with significantly decreased pressure values in the NRFI group.
ConclusionsOur study demonstrated lower pressure parameters in children with NRFI. In patients with normal resting pressures, 3D-HRAM may reveal segments with decreased pressures, which may play a potential role in the pathomechanism of incontinence.
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