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Children with Cystic Fibrosis (CF) are more likely to have intestinal dysbiosis due to recurrent antibiotic therapy and the conventional hypercaloric diet administered to them. This study aimed at evaluating the effect of isolated prebiotic components and probiotic strains, and their combinations as potential synbiotics, on the intestinal microbiota of CF children. A static in vitro colonic fermentation model was used by colonizing vials with faecal inoculum, a culture medium, and the substrates to be tested. Post treatment, aliquots were taken to determine ammonium, lactate, and short-chain fatty acids production and to profile the microbiota composition by 16s rRNA sequencing. At genus level, Escherichia-Shigella decreased (15.8%) with the treatment pectin + L. rhamnosus, followed by the beta-glucan + L. salivarius (15.5%). Inversely, the most increase in Bacteroides (44%) was obtained by the treatment with Pectin + L. reuteri. Lactate and acetic acid production was significantly increased with prebiotics and their combinations with L. rhamnosus and L. salivarius. In conclusion, the use of beta-glucan and pectin in combination with probiotic strains from the Lactobacillaceae family suggest potential to modulate dysbiosis and metabolic activity on CF colonic microbiota, encouraging further studies in animal studies or clinical settings to confirm the findings in vivo.
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Colo , Fibrose Cística , Microbioma Gastrointestinal , Prebióticos , Probióticos , Humanos , Fibrose Cística/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Criança , Colo/microbiologia , Colo/metabolismo , Fezes/microbiologia , Masculino , Fermentação , Ácidos Graxos Voláteis/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Feminino , Disbiose/microbiologia , Pectinas/metabolismo , Pectinas/farmacologiaRESUMO
BACKGROUND: Fat malabsorption in children with cystic fibrosis (CF) leads to poor nutritional status and altered colonic microbiota. This study aimed at establishing the faecal lipid profile in children with CF, and exploring associations between the faecal lipidome and microbiota. METHODS: Cross-sectional observational study with children with CF and an age-matched control group. Faecal lipidome was analysed by UHLC-HRMS and microbiota profiling by 16S rRNA amplicon sequencing. RESULTS: Among 234 identified lipid species, five lipidome clusters (LC) were obtained with significant differences in triacylglycerols (TG), diacylglycerols (DG), monoacylglycerols (MG) and fatty-acids (FA): LC1 subjects with good digestion and absorption: low TG and low MG and FA; LC2 good digestion and poor absorption: low TG and high MG and FA; LC3 Mild digestion and poor absorption: intermediate TG and high MG and FA; LC4 poor digestion and absorption: high TG and high MG and FA; LC5 outliers. Bacteroidota and Verrucomicrobiota decreased over LC1-LC4, while Proteobacteria increased. Nutritional status indicators were significantly higher in LC1 and decreased over LC2-LC4. CONCLUSION: Assessing faecal lipidome may be relevant to determine how dietary lipids are digested and absorbed. This new evidence might be a method to support targeted nutritional interventions towards reverting fat maldigestion or malabsorption. IMPACT: Lipidomic analysis enabled the identification of the lipid species related to maldigestion (triglycerides) or malabsorption (monoglycerides and fatty acids). Children with cystic fibrosis can be grouped depending on the faecal lipidome profile related to dietary fat maldigestion or malabsorption. The lipidome profile in faeces is related to the composition of microbiota and nutritional status indicators.
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OBJECTIVE: Intestinal inflammation with contradictory data on faecal calprotectin (fCP) levels is documented in patients with cystic fibrosis (CF). The aim of this study was to longitudinally evaluate fCP in a cohort of children with CF and their relationship with clinical variables. DESIGN: Prospective observational study to assess evolution of fCP levels, primary aimed at improving fat absorption. Along 1.5 years of follow-up (November 2016-May 2018) with four study visits pertaining to a pilot study (two of four) and to a clinical trial (two of four), the study outcomes were measured. SETTING: Six European CF centres in the context of MyCyFAPP Project. SUBJECTS: Children with CF and pancreatic insufficiency (2-18 years old). MAIN OUTCOME MEASUREMENTS: fCP levels, pulmonary function (percentage of forced expiratory volume in 1 s (FEV1%)) and coefficient of fat absorption (CFA). Additionally, in the last two visits, gastrointestinal (GI) symptoms were evaluated through the PedsQL-GI Questionnaire. Linear mixed regression models were applied to assess association between fCP and FEV1, CFA and GI symptoms. RESULTS: Twenty-nine children with CF and pancreatic insufficiency were included. fCP levels were inversely associated with total modified specific PedsQL-GI score (p=0.04) and positively associated with diarrhoea (p=0.03), but not with CFA. Along the four study visits, fCP significantly increased (from 62 to 256 µg/g) and pulmonary function decreased (from 97% to 87%), with a significant inverse association between the two study outcomes (p<0.001). CONCLUSIONS: In children with CF, fCP levels are inversely associated with pulmonary function and thus the specificity of fCP as a marker of intestinal inflammation in paediatric patients with CF warrants further investigation.
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Fibrose Cística , Fezes , Complexo Antígeno L1 Leucocitário , Humanos , Fibrose Cística/fisiopatologia , Fibrose Cística/metabolismo , Complexo Antígeno L1 Leucocitário/análise , Criança , Fezes/química , Feminino , Masculino , Estudos Prospectivos , Pré-Escolar , Adolescente , Europa (Continente) , Biomarcadores/análise , Biomarcadores/metabolismo , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/etiologia , Volume Expiratório Forçado/fisiologiaRESUMO
BACKGROUND: Children with cystic fibrosis (CF) present with gut dysbiosis, and current evidence impedes robust recommendations on the use of prebiotics. This study aimed at establishing the prebiotic potential of a commercial beta-glucan on the in vitro colonic microbiota of a child with CF compared to a healthy counterpart (H). METHODS: A dynamic simulator of colonic fermentation (twin-SHIME® model) was set up including the simulation of the proximal (PC) and distal colon (DC) of the CF and the H subjects by colonizing the bioreactors with faecal microbiota. During two weeks the system was supplied with the beta-glucan. At baseline, during treatment and post-treatment, microbiota composition was profiled by 16 S rRNA and short-chain fatty acids (SCFA) production was determined by GS-MS. RESULTS: At baseline, Faecalibacterium, was higher in CF' DC than in the H, along higher Acidaminococcus and less Megasphaera and Sutterella. Beta-glucan supplementation induced increased microbiota richness and diversity in both subjects during the treatment. At genus level, Pseudomonas and Veillonella decreased, while Akkermansia and Faecalibacterium increased significantly in CF. CONCLUSION: The supplementation with beta-glucan suggests positive results on CF colonic microbiota in the in vitro context, encouraging further research in the in vivo setting. IMPACT: Current evidence supports assessing the effect of prebiotics on modifying cystic fibrosis microbiota. The effect of beta-glucan supplementation was evaluated in a controlled dynamic in vitro colonic ecosystem. Beta-glucan supplement improved diversity in cystic fibrosis colonic microbiota. The treatment showed increased abundance of Faecalibacterium and Akkermansia in cystic fibrosis. New evidence supports the use of prebiotics in future clinical studies.
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A "high-fat, high-energy diet" is commonly recommended for children with cystic fibrosis (CF), leading to negative consequences on dietary patterns that could contribute to altered colonic microbiota. The aim of this study was to assess dietary intake and to identify possible associations with the composition of faecal microbiota in a cohort of children with CF. A cross-sectional observational study was conducted, including a 3-day food record simultaneously with the collection of faecal samples. The results showed a high fat intake (43.9% of total energy intake) and a mean dietary fibre intake of 10.6 g/day. The faecal microbiota was characterised at the phylum level as 54.5% Firmicutes and revealed an altered proportion between Proteobacteria (32%) and Bacteroidota (2.2%). Significant associations were found, including a negative association between protein, meat, and fish intake and Bifidobacterium, a positive association between lipids and Escherichia/Shigella and Streptococcus, a negative association between carbohydrates and Veillonella and Klebsiella, and a positive association between total dietary fibre and Bacteroides and Roseburia. The results reveal that a "high-fat, high-energy" diet does not satisfy dietary fibre intake from healthy food sources in children with CF. Further interventional studies are encouraged to explore the potential of shifting to a high-fibre or standard healthy diet to improve colonic microbiota.
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Fibrose Cística , Microbiota , Criança , Animais , Humanos , Dieta , Estudos Transversais , Fibras na Dieta/análise , Dieta Hiperlipídica , Ingestão de AlimentosRESUMO
Cystic Fibrosis-related gut dysbiosis (CFRGD) has become a recognised complication in children with this condition, and current evidence remains insufficient to guide the selection of probiotic strains for supplementation treatments. The aim of this study was to characterise the effect of three probiotic strains on CFRGD by means of a dynamic in vitro simulation of the colonic fermentation (SHIME®). The configuration of the system included three bioreactors colonised with the faecal inoculum of a child with cystic fibrosis. For 20 days, each bioreactor was supplied daily with either Lacticaseibacillus rhamnosus GG (ATCC 53103 TM), Limosilactobacillus reuteri (DSM 17938) or Lactiplantibacillus plantarum (DSM 22266). The baseline microbiota was characterised by a high abundance of Prevotella, Faecalibacterium and Acidaminococcus genera. After 20 days of supplementation, L. rhamnosus and L. plantarum reduced Prevotella significantly, and the three strains led to increased Faecalibacterium and Bifidobacterium and decreased Acidaminococcus, with some of these changes being maintained 10 days after ceasing supplementation. The metabolic activity remained unaltered in terms of short-chain fatty acids, but branched-chain fatty acids showed a significant decrease, especially with L. plantarum. Additionally, ammonia decreased at 20 days of supplementation, and lactate continuously increased with the three strains. The effects on colonic microbiota of L. rhamnosus, L. reuteri or L. plantarum were established, including increased beneficial bacteria, such as Faecalibacterium, and beneficial metabolites such as lactate; and on the other hand, a reduction in pathogenic genera, including Prevotella or Acidaminococcus and branched-chain fatty acids, overall supported their use as probiotics in the context of CFRGD.
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Fibrose Cística , Limosilactobacillus reuteri , Microbiota , Criança , Humanos , Lactobacillaceae , Ácido Láctico , Disbiose , Faecalibacterium , Ácidos GraxosRESUMO
Microalgae contain a diverse range of high-value compounds that can be utilized directly or fractionated to obtain components with even greater value-added potential. With the use of microalgae for food and medical purposes, there is a growing interest in their digestive properties and impact on human gut health. The extraction, separation, and purification of these components are key processes in the industrial application of microalgae. Innovative technologies used to extract and purify microalgal high-added-value compounds are key for their efficient utilization and evaluation. This review's comprehensive literature review was performed to highlight the main high-added-value microalgal components. The technologies for obtaining bioactive compounds from microalgae are being developed rapidly, various innovative, efficient, green separation and purification technologies are emerging, thus helping in the scaling-up and subsequent commercialization of microalgae products. Finally, the digestive behavior of microalgae nutrients and their health effects on the human gut microbiota were discussed. Microalgal nutrients exhibit favorable digestive properties and certain components have been shown to benefit gut microbes. The reality that must be faced is that multiple processes are still required for microalgae raw materials to final usable products, involving energy, time consumption and loss of ingredients, which still face challenges.
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The impact of Spirulina, Chlorella and Phaeodactylum tricornutum (P. tricornutum) microalgal extracts obtained by pressurized liquid extraction (PLE) on antioxidant and anti-inflammatory activities, microbial growth and in vitro gut microbiota composition was evaluated. PLE, compared to conventional extraction, led to a significant (p < 0.05) increase in proteins, carbohydrates, polyphenols, and antioxidant capacities of the three microalgal extracts. Moreover, Spirulina and P. tricornutum extracts significantly (p < 0.05) reduced the in vitro activation of the inflammatory NF-κB pathway. The microalgal extracts had also an inhibitory effect on the pathogenic bacteria while potential beneficial Lactobacillus and Bifidobacterium strains increased growth. The effects of microalgal extracts on specific bacterial groups were analyzed by quantitative PCR technology, and bacterial gene copy numbers were affected by in vitro digestion process and colonic fermentation time. GC-MS results showed that microalgal biomolecules' digestion promoted the release of short-chain fatty acids (SCFAs) during in vitro colonic microbiota fermentation, particularly acetic, butanoic and propanoic, indicating that the biomolecules in microalgae extracts have potential health benefits for human gut.
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Chlorella , Microbioma Gastrointestinal , Microalgas , Spirulina , Humanos , Chlorella/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Spirulina/metabolismo , NF-kappa B/metabolismo , Microalgas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , CarboidratosRESUMO
BACKGROUND: low evidence on the dose of enzymatic supplements used in pancreatic enzyme replacement therapy (PERT) is available. AIM: assessing if fat, protein and starch absorption could be related to the dose of the enzymatic supplement, the intra-patient variability in the dose and macronutrient intake. METHODS: Four-day food records and 3-day faecal samples were prospectively collected in 69 children with cystic fibrosis. Pearson correlations between enzyme dose and macronutrient absorption, and beta regression models were applied to explain the results. RESULTS: the supply of protease units per protein intake (PU/g protein) in relation to lipase units per fat intake (LU/g fat) was low and the intra-patient variability in the dose of enzymes was ±1331 LU/g fat. Fat and starch absorption was >90% while for protein it was 81.5%. The coefficient of fat absorption was associated with an interaction between the dose of LU/g fat and its variability among different days. Lipid and protein intake were also determinants of the coefficient of fat absorption. CONCLUSION: the dose of PERT should be re-adjusted to the amount of dietary fat of every meal (constant LU/g fat) to minimize variability and increase fat absorption. Also, the supply of protease should be increased to prevent from protein malabsorption.
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Fibrose Cística , Insuficiência Pancreática Exócrina , Humanos , Criança , Fibrose Cística/tratamento farmacológico , Fibrose Cística/complicações , Pâncreas , Gorduras na Dieta , Terapia de Reposição de Enzimas/métodos , Peptídeo Hidrolases/uso terapêutico , Nutrientes , Insuficiência Pancreática Exócrina/complicaçõesRESUMO
Digestion and the absorption of food compounds are necessary steps before nutrients can exert a role in human health. The absorption and utilization of nutrients in the diet is an extremely complex dynamic process. Accurately grasping the digestion and absorption mechanisms of different nutrients or bioactive compounds can provide a better understanding regarding the relationship between health and nutrition. Several in vitro models for simulating human gastrointestinal digestion and colonic fermentation have been established to obtain more accurate data for further understanding of the metabolism of dietary components. Marine media is rich in a wide variety of nutrients that are essential for humans and is gaining increased attention as a research topic. This review summarizes some of the most explored in vitro digestion and colonic fermentation models. It also summarizes the research progress on the digestion and absorption of nutrients and bioactive compounds from marine substrates when subjected to these in vitro models. Additionally, an overview of the changes imparted by the digestion process on these bioactive compounds is provided, in order to support those marine resources that can be utilized for developing new healthy foods.
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Colo , Digestão , Colo/metabolismo , Dieta , Fermentação , Humanos , NutrientesRESUMO
Objectives: The fatty acid (FA) composition of breast milk is a relevant aspect related to the development of the lactating infant. The present study aimed at exploring correlations between dietary intake of macro- and micronutrients with the FA profile in breast milk, and the possible implication for infants' growth. Study Design: Breast milk samples from a cohort of lactating women were collected 7-15 days postpartum. The FA profiles in triacylglycerol (TAG) and phospholipid (PL)-rich fractions were analyzed by gas chromatography. Diet was registered during the third trimester of pregnancy by means of a food frequency questionnaire (FFQ). In addition, anthropometric measurements of infants were collected from gestation and up to 12 months postpartum. Results: The FA profile in breast milk was characterized by a median of 37.4, 41.3 and 16.8% of saturated, monounsaturated, and polyunsaturated FAs, respectively. From the dietary components, zinc, iron, and B group vitamins were correlated positively with the proportion of total n-3 FAs in TAG and C20:5 n-3 in PL. Lycopene, vitamin E, zinc, and vitamin B2 showed a similar correlation with total polyunsaturated fatty acid (PUFA), total n-6 FAs, C20:4 n-6, and C18:2 n-6 in TAG. Regarding food groups, nuts showed the strongest association with several PUFA both in TAG and PL, while the vegetable group was also positively associated with C18:3 n-3. Furthermore, the concentration of linolenic acid (C18:3 n-3) and palmitic acid (C16:0) were positively associated with increased length for age (LFA) and weight for age (WFA) at 12 months compared with birth [ΔLFA -0.16 (-0.85, 0.37); ΔWFA -0.26 (-0.77, 0.21)]. Conclusions: Mothers' intake of nuts, dietary sources of zinc, iron, and B group vitamins were identified as potential predictors of a high-unsaturated FA profile in breast milk. In addition, linolenic and palmitic acids in breast milk were positively associated with infants' growth in the first year of life.
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Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.
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Doença Celíaca , Autoanticorpos , Biópsia , Criança , Proteínas de Ligação ao GTP , Humanos , Imunoglobulina A , Mucosa Intestinal , Proteína 2 Glutamina gama-Glutamiltransferase , TransglutaminasesRESUMO
Breastfeeding is key for infant development and growth. Breast milk contains different bioactive compounds including antibodies. Recent studies have demonstrated the presence of breast milk SARS-CoV-2 antibodies after maternal infection and vaccination. However, the potential impact on the infant has not been explored yet. As a first step, we aimed at assessing the potential persistence of SARS-CoV-2 IgA and IgG antibodies from infected and vaccinated women in the gastrointestinal tract of the infants by means of an in vitro-simulated gastrointestinal digestion approach. Breast milk samples from 10 lactating women receiving mRNA vaccination against SARS-CoV-2 (n = 5 with BNT162b2 mRNA and n = 5 with mRNA-1273) and also, COVID-19 infected (n = 5) were included. A control group with women with no exposure to the virus (n = 10 pre-pandemic) were also studied. The presence of IgA and IgG SARS-CoV-2 antibody levels was determined by ELISA after the gastric and intestinal stages. The impact of digested antibodies on infant gut microbiota was tested by simulating colonic fermentation with two different fecal inoculums: infants from vaccinated and non-vaccinated mothers. Specific gut microbial groups were tested by targeted qPCR. In vitro infant gastrointestinal digestion significantly decreased the levels of both anti-SARS-CoV-2 IgA and IgG. However, both remained resistant in all the study groups except in that evaluating breast milk samples from infected women, in which IgG was degraded below the cut-off values in the intestinal phase. No effect of the antibodies on microbiota were identified after digestion. In conclusion, antibody levels against SARS-CoV-2 are reduced after in vitro-simulated gastrointestinal tract but remain present, so a positive biological effect could be expected from this infant immunization pathway.
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COVID-19 , Leite Humano , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Criança , Digestão , Feminino , Humanos , Imunoglobulina A , Imunoglobulina G , Lactente , Lactação , RNA Mensageiro , SARS-CoV-2RESUMO
Fermentation of plant-based substrates with edible fungi enhances the nutrient profile and digestibility, but it has been scarcely applied to edible seeds, which are rich in healthy lipids. In this study, chia and sesame seeds were solid-state fermented with Pleurotus ostreatus, followed by drying and milling. Fermentation led to increased content of lipid and protein in both seeds' products, and a change in fatty acid profile in favor of increased polyunsaturated fatty acids. Then, the samples were subjected to in vitro digestion. Lipolysis, determined by nuclear magnetic resonance, was higher in sesame than in chia products, and the fermented counterparts had increased values compared to the controls. In terms of physical properties, fermentation showed reduced particle size and increased matrix degradation and decreased viscosity of the digestion medium, which were related to increased lipolysis. In conclusion, applying solid-state fermentation on chia and sesame seeds could be a recommendable approach.
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Human milk (HM) is the gold standard for infant nutrition during the first months of life. Beyond its nutritional components, its complex bioactive composition includes microorganisms, their metabolites, and oligosaccharides, which also contribute to gut colonization and immune system maturation. There is growing evidence of the beneficial effects of bacteria present in HM. However, current research presents limited data on the presence and functions of other organisms. The potential biological impacts on maternal and infant health outcomes, the factors contributing to milk microbes' variations, and the potential functions in the infant's gut remain unclear. This review provides a global overview of milk microbiota, what the actual knowledge is, and what the gaps and challenges are for the next years.
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Human milk is the gold standard for infant nutrition during the first months of life since it is perfectly adapted to the neonatal nutritional requirements and supports infant growth and development. Human milk contains a complex nutritional and bioactive composition including microorganisms and oligosaccharides which would also contribute to the gut and immune system maturation. Despite the growing evidence, the factors contributing to milk microbes' variations and the potential functions on the infant's gut are still uncovered. This short-review provides a general overview of milk microbiota, potential factors shaping its composition, contribution to the infant microbiota and immune system development, including the suggested biological relevance for infant health as well as the description of tools and strategies aimed to restore and module microbes in milk.
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Microbioma Gastrointestinal , Microbiota , Aleitamento Materno , Feminino , Humanos , Lactente , Saúde do Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Leite HumanoRESUMO
Cystic Fibrosis (CF) is a life-long genetic disease, causing increased energy needs and a healthy diet with a specific nutrient distribution. Nutritional status is an indicator of disease prognosis and survival. This study aimed at assessing the effectiveness of a self-management mobile app in supporting patients with CF to achieve the dietary goals set by the CF nutrition guidelines. A clinical trial was conducted in pancreatic insufficient children with CF, followed in six European CF centres, where the self-management app developed within the MyCyFAPP project was used for six months. To assess secondary outcomes, three-day food records were compiled in the app at baseline and after 3 and 6 months of use. Eighty-four subjects (mean 7.8 years old) were enrolled. Compared to baseline, macronutrient distribution better approximated the guidelines, with protein and lipid increasing by 1.0 and 2.1% of the total energy intake, respectively, by the end of the study. Consequently, carbohydrate intake of the total energy intake decreased significantly (-2.9%), along with simple carbohydrate intake (-2.4%). Regarding food groups, a decrease in ultra-processed foods was documented, with a concomitant increase in meat and dairy. The use of a self-management mobile app to self-monitor dietary intake could become a useful tool to achieve adherence to guideline recommendations, if validated during a longer period of time or against a control group.
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Fibrose Cística , Ingestão de Alimentos , Nutrientes , Autogestão , Telemedicina/métodos , Criança , Pré-Escolar , Dieta , Comportamento Alimentar , Feminino , Humanos , Masculino , Aplicativos Móveis , Política Nutricional , Estado NutricionalRESUMO
BACKGROUND: Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. METHODS: In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. RESULTS: In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). CONCLUSIONS: Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. IMPACT: Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.
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Fibrose Cística/complicações , Gorduras na Dieta/metabolismo , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/dietoterapia , Fezes/química , Absorção Intestinal , Pâncreas/enzimologia , Adolescente , Criança , Terapia Combinada , Fibrose Cística/diagnóstico , Fibrose Cística/enzimologia , Terapia de Reposição de Enzimas/efeitos adversos , Europa (Continente) , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/enzimologia , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Projetos Piloto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Patients with cystic fibrosis (CF) and pancreatic insufficiency need pancreatic enzyme replacement therapy (PERT) for dietary lipids digestion. There is limited evidence for recommending the adequate PERT dose for every meal, and controlling steatorrhea remains a challenge. This study aimed to evaluate a new PERT dosing method supported by a self-management mobile-app. METHODS: Children with CF recruited from 6 European centres were instructed to use the app, including an algorithm for optimal PERT dosing based on in vitro digestion studies for every type of food. At baseline, a 24h self-selected diet was registered in the app, and usual PERT doses were taken by the patient. After 1 month, the same diet was followed, but PERT doses were indicated by the app. Change in faecal fat and coefficient of fat absorption (CFA) were determined. RESULTS: 58 patients (median age 8.1 years) participated. Baseline fat absorption was high: median CFA 96.9%, median 2.4g faecal fat). After intervention CFA did not significantly change, but range of PERT doses was reduced: interquartile ranges narrowing from 1447-3070 at baseline to 1783-2495 LU/g fat when using the app. Patients with a low baseline fat absorption (CFA<90%, n=12) experienced significant improvement in CFA after adhering to the recommended PERT dose (from 86.3 to 94.0%, p=0.031). CONCLUSION: the use of a novel evidence-based PERT dosing method, based on in vitro fat digestion studies incorporating food characteristics, was effective in increasing CFA in patients with poor baseline fat absorption and could safely be implemented in clinical practice.
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Fibrose Cística/tratamento farmacológico , Dieta , Terapia de Reposição de Enzimas/métodos , Aplicativos Móveis , Pâncreas/enzimologia , Criança , Europa (Continente) , Medicina Baseada em Evidências , Feminino , Humanos , MasculinoRESUMO
Salmon is the main dietary source of omega-3 lipids and contains high-biological value protein. However, processing techniques could affect macronutrient digestibility. Also, altered intestinal conditions, particularly given in pancreatic insufficiency, could threaten digestibility. This study tested both hypotheses by subjecting raw, marinated and microwave-cooked salmon to static in vitro digestion under healthy (pH 7, bile concentration 10 mM) and altered (pH 6, bile 1 or 10 mM) intestinal conditions with different pancreatin concentrations. In the standard conditions, proteolysis was not affected by processing, but lipolysis decreased in marinated (46%) and raw salmon (57%) compared to the cooked matrix (67%). In altered conditions, proteolysis and lipolysis decreased to different extents depending on the treatment. Overall, processing affected proteolysis the most (f-ratio = 5.86), while intestinal conditions were the major determinants of lipolysis (f-ratio = 58.01). This study could set the ground to establish dietary recommendations of salmon for specific population groups.