Nutritional aspects and gut microbiota in paediatric inflammatory bowel disease

As Crohn’s disease (CD) is a disease of the gastrointestinal tract, nutrition is very important and is implicated in several aspects of the disease, from aetiology, management, and the long-term health of the patient. Nutritional therapy with EEN is the mainstream approach in the management of active paediatric CD and has a dual effect, inducing clinical remission and providing nutritional support and rehabilitation. Although its efficacy is well established by human trials and clinical experience, the mode of action remains unknown. Initial speculations for a mechanism of action mediated through gut rest, and protein/energy reconstitution have not been established. On the other hand the strong evidence for the role of the indigenous microbiota and micronutrients in disease aetiology and mucosal injury, challenged the researcher to explore whether the action of EEN is mediated through changes in these parameters. This study aimed to assess aspects of the nutritional status of paediatric patients with inflammatory bowel disease (IBD), to appraise the use of nutritional remedies in the same population, and to explore putative mechanisms of action of EEN, the nutritional therapy, with the most robust evidence of clinically efficacy. The first of these studies was a questionnaire survey which assessed the use of special diets, nutritional supplements, herbals, and alternative medicine in a representative sample of paediatric patients with IBD. Use of these treatments was declared by two thirds of the patients with probiotic use and dairy free diet being the commonest forms used. Prevalence of anaemia and predictors of its progress at six and 12 months were assessed in a large retrospective case review study. Anaemia was as high as 73% of patients at diagnosis and haemoglobin concentration improvement at six and 12 post diagnosis was associated with the use of oral iron supplementation, improvement of nutritional status markers, growth, and systemic markers of disease activity. In a mechanistic study the validity of a bedside method, used to assess the body composition of children with CD, was compared against a reference method. The agreement of the two methods was low and the inter-individual bias between them was substantial. The aim of this thesis was to study the effect of EEN on gut microbiota diversity, bacterial metabolic activity, inflammatory response and nutritional status in paediatric patients with active CD. Newly diagnosed children with active CD, and patients with longstanding disease, on clinical relapse, who started treatment with EEN as part of their standard clinical management, were recruited. Four stool samples were collected while on treatment with EEN and one when the patient returned to their normal diet. Bacterial diversity was assessed with molecular microbiology techniques, and bacterial metabolites were measured in serial stool samples and correlated with faecal calprotectin levels, systemic inflammatory markers and clinical activity. A single stool sample was collected from their first-degree relatives and two serial samples from healthy children with no family history of IBD. Significant changes were observed for the metabolic activity of the commensal microbiota during the course of treatment. In particular, faecal butyrate significantly decreased by more than 100%, faecal pH moved into the alkaline range, and a five-fold increase was observed in total sulphide but only in those patients who achieved clinical remission, or in whom faecal calprotectin levels decreased at the end of treatment. No such changes were observed in children who did not achieve complete clinical remission or when the treatment failed. Gut bacterial diversity did not change significantly during treatment, but was significantly lower than in healthy children, who also presented a higher degree of similarity between the two serial samples. Interestingly the gut microbiota of the healthy first degree relatives of CD children had significantly lower bacterial diversity compared with the healthy children but no such difference was observed compared with their CD relatives. The majority of the healthy relatives had also significantly high levels of calprotectin suggesting intestinal inflammation but no clinical presentation of gastrointestinal disease. A secondary outcome of this study was to measure changes in the systemic and gut specific markers of disease activity during treatment. Although systemic markers of disease activity improved to normal levels in the majority of the patients, intestinal inflammation was still ongoing and only one of the 16 children had normal calprotectin levels at the end of EEN. Moreover, only in those patients who achieved clinically complete remission, did calprotectin levels decrease significantly at the end of treatment. From the same cohort of patients three blood samples were also collected before, at the end of treatment and on normal diet. Changes in the concentration of 19 different micronutrients were measured in the serum and some in erythrocytes and correlated with systemic markers of disease activity. Serial changes in anthropometry and body composition were assessed during EEN and correlated with disease activity markers. Body weight increased in all patients at the end of treatment but fat free mass significantly increased only in those patients who entered in clinical remission. Several micronutrients and mainly antioxidants were below the reference range for the majority of patients at the time of treatment initiation. Most of them improved by the end of treatment but the serum concentration of carotenoids further deteriorated with more than 90% of the patients presenting concentration lower than the lower sensitivity level of the assay. A strong association was found between systemic markers of disease activity and antioxidant vitamins, but not with intestinal inflammation. In conclusion, paediatric patients with IBD, and mainly those with CD present with suboptimal protein/energy status, anaemia, and low circulating levels for many antioxidants. Treatment with EEN corrected the majority of these markers of nutritional status but the carotenoid levels deteriorated. Although the improvement in the serum levels of some micronutrients can be an epiphenomenon of the acute phase response, it does not explain the depleted levels of carotenoids at the end of EEN. This may be attributed to the lack of carotenoids in the feeds used in conjunction with excessive utilisation during the active course of the disease. On the other hand, the unhealthy intestinal microenvironment observed, in only those patients who clinically improved at the end of treatment; do not support a prebiotic mode of EEN action, as was proposed by a recent Italian study. These changes may be a secondary phenomenon, associated with changes in gut motility, better absorption of butyrate with disease improvement, or changes in the availability of colonic bacterial substrates. Alternatively these changes may be associated with changes in the microbiota composition and production of so far unknown bacterial bioproducts which may have a causative association with the onset and propagation of intestinal inflammation in CD. These results may have significant implications in manufacturers of clinical nutrition products. Addition of carotenoids may improve the provision of antioxidant micronutrients and a dual nutritional therapy combining EEN with prebiotics, butyrate supplementation, or probiotics may increase the efficacy of the existing formulae. This should be addressed in future studies

Dietitians’ perceptions and experience of blenderised feeds for paediatric tube-feeding

Objective: There is an emerging interest in the use of blenderised food for tube-feeding (BFTF). This survey explored paediatric dietitians' perceptions and experiences of BFTF use. Design: A web-based questionnaire was distributed to the Paediatric group of the British Dietetic Association. The survey captured dietitians' personal opinions and experience supporting children on BFTF, and the perceptions of carers. Results: Of the 77 respondents, 19 were aware of professional guidelines and 63 had never received training on BFTF. Thirty-four would not recommend BFTF and 11 would advise against its use; yet 43 would recommend it to supplement commercial feeds. Fifty-seven would change their perception about BFTF if there were evidence-based guidelines. Forty-four would feel confident to support a patient using BFTF. Forty-three had previous experience supporting a patient with BFTF. The main concerns perceived by dietitians, pertinent to the use of BFTF, were nutritional inadequacy (n=71), tube blockages (n=64) and increased infection risk (n=59) but these were significantly higher than those experienced by themselves in clinical practice (p<0.001 for all three). A reduction in reflux and vomiting and increased carer involvement were the main perceived and observed benefits by both dietitians and carers. Conclusions: The use of these feeds for tube-fed children is increasingly being seen as a viable choice. Dietitians experienced significantly fewer issues with the use of BFTF in clinical practice compared with their self-reported apprehensions in the survey. Well-controlled studies are now needed to objectively assess the benefits, risks, costs and practicality of BFTF

Impact of phenylketonuria type meal on appetite, thermic effect of feeding and postprandial fat oxidation

Background: Dietary management of phenylketonuria (PKU) requires the replacement of natural protein-containing foods with special low protein foods. The effect of a PKU type diet on factors contributing to energy balance requires investigation. Objective: To investigate the impact of a PKU type meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation. Methods: Twenty-three healthy adults (mean ± SD age: 24.3 ± 5.1 years; BMI: 22.4 ± 2.5 kg/m2) participated in a randomized, crossover design study. Each participant conducted two (PKU and Control) experimental trials which involved consumption of a PKU type meal and protein substitute drink or an isocaloric and weight matched ordinary meal and protein-enriched milk. Appetite, metabolic rate, fat oxidation measurements and blood collections were conducted for the duration of 300 min. On the completion of the measurements ad libitum buffet dinner was served. Results: Responses of appetite ratings, plasma concentrations of GLP-1 and PYY (P > 0.05, trial effect, two-way ANOVA) and energy intake during ad libitum buffet dinner (P > 0.05, paired t-test) were not significantly different between the two trials. The TEF (PKU, 10.2 ± 1.5%; Control, 13.2 ± 1.0%) and the total amount of fat oxidized (PKU, 18.90 ± 1.10 g; Control, 22.10 ± 1.10 g) were significantly (P < 0.05, paired t-tests) lower in the PKU than in the Control trial. The differences in TEF and fat oxidation were significant (P < 0.05, paired t-tests) for the post-meal period. Conclusions: Consumption of a meal composed of special low protein foods has no detrimental impact on appetite and appetite hormones but produces a lower TEF and postprandial fat oxidation than an ordinary meal. These metabolic alterations may contribute to the increased prevalence of obesity reported in patients with PKU on contemporary dietary management

Response of appetite and potential appetite regulators following intake of high energy nutritional supplements

Background: The net clinical benefit of high-energy nutritional supplements (HENSDs) consumption is lower than expected. Objectives: To investigate the extent to which consumption of oral HENSD in the fasted state reduces energy intake in slim females during consecutive breakfast and lunch, and whether this relates to changes in appetite and metabolic appetite regulators. Design: Twenty three females of 24.4 ± 2.8 years with BMI of 18.2 ± 0.8 kg/m2 consumed HENSD (2.5 MJ) or PLACEBO (0.4 MJ) in fasted state in a single blind randomized cross-over study. Appetite and metabolic rate measurements and blood collection were conducted prior to and during 240 min after the intake of the supplements. Energy intake was recorded during ad libitum buffet breakfast and lunch served 60 min and 240 min post supplementation respectively. Results: Energy intake during breakfast was significantly (P < 0.01) lower in the HENSD trial but the net cumulative effect on energy intake was 1.07 ± 0.34 MJ higher in the HENSD compared to PLACEBO. Plasma concentration of CCK and PYY and insulin and were significantly (P < 0.05) higher in the HENSD trial while appetite measures were not significantly different between HENSD and PLACEBO trials. Correlations for the within participant relations between the responses of plasma hormones and appetite scores were significant (P < 0.05) for PYY and insulin but not CCK. The energy expended aboveresting metabolic rate was significantly (P < 0.05) higher in the HENDS trial but relative increase in energy expenditure was not significantly different between the two trials. Conclusion: Oral high-energy nutritional supplements have a partial and relatively short lived suppressive action on energy intake and can be expected to increase net energy intake by approximately half the energy value of the supplement consumed

An automated identification and analysis of ontological terms in gastrointestinal diseases and nutrition-related literature provides useful insights

With an unprecedented growth in the biomedical literature, keeping up to date with the new developments presents an immense challenge. Publications are often studied in isolation of the established literature, with interpretation being subjective and often introducing human bias. With ontology-driven annotation of biomedical data gaining popularity in recent years and online databases offering metatags with rich textual information, it is now possible to automatically text-mine ontological terms and complement the laborious task of manual management, interpretation, and analysis of the accumulated literature with downstream statistical analysis. In this paper, we have formulated an automated workflow through which we have identified ontological information, including nutrition-related terms in PubMed abstracts (from 1991 to 2016) for two main types of Inflammatory Bowel Diseases: Crohn’s Disease and Ulcerative Colitis; and two other gastrointestinal (GI) diseases, namely, Coeliac Disease and Irritable Bowel Syndrome. Our analysis reveals unique clustering patterns as well as spatial and temporal trends inherent to the considered GI diseases in terms of literature that has been accumulated so far. Although automated interpretation cannot replace human judgement, the developed workflow shows promising results and can be a useful tool in systematic literature reviews. The workflow is available at https://github.com/KociOrges/pytag

Optimal distribution and utilization of donated human breast milk: a novel approach

Background: The nutritional content of donated expressed breast milk (DEBM) is variable. Using DEBM to provide for the energy requirements of neonates is challenging. Objective: The authors hypothesized that a system of DEBM energy content categorization and distribution would improve energy intake from DEBM. Methods: We compared infants’ actual cumulative energy intake with projected energy intake, had they been fed using our proposed system. Eighty-five milk samples were ranked by energy content. The bottom, middle, and top tertiles were classified as red, amber, and green energy content categories, respectively. Data on 378 feeding days from 20 babies who received this milk were analyzed. Total daily intake of DEBM was calculated in mL/kg/day and similarly ranked. Infants received red energy content milk, with DEBM intake in the bottom daily volume intake tertile; amber energy content milk, with intake in the middle daily volume intake tertile; and green energy content milk when intake reached the top daily volume intake tertile. Results: Actual median cumulative energy intake from DEBM was 1612 (range, 15-11 182) kcal. Using DEBM with the minimum energy content from the 3 DEBM energy content categories, median projected cumulative intake was 1670 (range 13-11 077) kcal, which was not statistically significant (P = .418). Statistical significance was achieved using DEBM with the median and maximum energy content from each energy content category, giving median projected cumulative intakes of 1859 kcal (P = .0006) and 2280 kcal (P = .0001), respectively. Conclusion: Cumulative energy intake from DEBM can be improved by categorizing and distributing milk according to energy content

Asthma causation and the gastrointestinal microbiome and metabolome: might there be a signal, or is it just noise?

No abstract available

Application of knee-bracing system on high-rise buildings

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2006.Includes bibliographical references (leaf 60).The need and ambition of humanity to go higher and higher is something that is amplified as time evolves. It is the same need that leads engineers to push their structures to higher limits. However, when engineers design higher structures their knowledge and their abilities are challenged. In that sense, during the design process of a high-rise building all the strange phenomenon of the behavior of the structure must be considered. A very significant factor that affects the limits of today's high-rise construction is the wind loading. Bracing the building in a clever and more efficient way was always a difficult task for designers and engineers. This thesis deals with a bracing system called the knee-bracing system. The application of knee-bracing system for high-rise buildings is not yet fully determined and this study will try to describe the problem and provide some solutions. Knee-bracing will be checked and the possibility of providing the required results using the minimum amount of material and giving the maximum space for use from the residents or workers of the building will be examined.(cont.) Several different cases of loading and knee-bracing systems are considered and an optimization for the design of such systems is described. The last part of the document describes the idea of adaptive stiffness, something new for high-rise buildings. Reinforcing these ideas, solutions for the construction of these bracings are also provided.by Symeon Gerasimidis.M.Eng

Analysis of 61 exclusive enteral nutrition formulas used in management of active Crohn's disease - new insights into dietary disease triggers

Background: Exclusive enteral nutrition (EEN) is an effective treatment for Crohn's disease. Aims: To investigate the hypothesis that ingredients of EEN formulas are unlikely to initiate a disease flare and that their dietary elimination is not essential for disease amelioration. Methods: We performed compositional analysis of EEN formulas with evidence of efficacy in management of active Crohn's disease. Macronutrient content was compared against the dietary reference values (DRV), the UK National Diet and Nutrition Survey (NDNS) and intake of Crohn's disease children. Food additives were cross‐referenced against the FAO/WHO database. Results: Sixty‐one formulas were identified with variable composition (carbohydrates [22.8%‐89.3%], protein [7.8%‐30.1%], fat [0%‐52.5%]). Maltodextrin, milk protein and vegetable/plant oils were the commonest macronutrient sources. Their n‐6:n‐3 fatty acid ratio varied from 0.25 to 46.5. 56 food additives were identified (median per formula: 11). All formulas were lactose‐free, gluten‐free, and 82% lacked fibre. The commonest food additives were emulsifiers, stabilisers, antioxidants, acidity regulators and thickeners. Food additives, implicated in Crohn's disease aetiology, were present in formulas (modified starches [100%], carrageenan [22%], carboxymethyl cellulose [13%] and polysorbate 80 [5%]). Remission rates did not differ between EEN formulas with and without those food additives. Analysis including only formulas from randomised controlled trials (RCTs) retained in the latest Cochrane meta‐analysis produced similar findings. EEN formulas contained less energy from saturated fat than NDNS intake. Conclusion: We have identified food ingredients which are present in EEN formulas that are effective in Crohn's disease and challenge perceptions that these ingredients might be harmful