Faecal lipid profile as a new marker of fat maldigestion, malabsorption and microbiota.


Journal

Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714

Informations de publication

Date de publication:
22 May 2024
Historique:
received: 12 09 2023
accepted: 28 03 2024
revised: 21 03 2024
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 22 5 2024
Statut: aheadofprint

Résumé

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. 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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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 CONCLUSIONS
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.

Identifiants

pubmed: 38778229
doi: 10.1038/s41390-024-03209-0
pii: 10.1038/s41390-024-03209-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Références

Elborn, S. Cystic fibrosis. Lancet 388, 2519–2531 (2016).
doi: 10.1016/S0140-6736(16)00576-6 pubmed: 27140670
Kalivianakis, M. et al. Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids. Am. J. Clin. Nutr. 69, 127–134 (1999).
doi: 10.1093/ajcn/69.1.127 pubmed: 9925134
Yen, E. H., Quinton, H. & Borowitz, D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J. Pediatr. 162, 530–535 (2013).
doi: 10.1016/j.jpeds.2012.08.040 pubmed: 23062247
Borowitz, D. et al. Gastrointestinal outcomes and confounders in cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 41, 273–285 (2005).
doi: 10.1097/01.mpg.0000178439.64675.8d pubmed: 16131979
Bass, R., Brownell, J. N. & Stallings, V. A. The impact of highly effective CFTR modulators on growth and nutrition status. Nutrients 13, 2907 (2021).
doi: 10.3390/nu13092907 pubmed: 34578785 pmcid: 8470943
Humbert, L. et al. Postprandial bile acid levels in intestine and plasma reveal altered biliary circulation in chronic pancreatitis patients. J. Lipid Res. 59, 2202–2213 (2018).
doi: 10.1194/jlr.M084830 pubmed: 30206181 pmcid: 6210915
Gelfond, D., Ma, C., Semler, J. & Borowitz, D. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig. Dis. Sci. 58, 2275–2281 (2013).
doi: 10.1007/s10620-012-2209-1 pubmed: 22592630
Hunter, J. E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids 36, 655–668 (2001).
doi: 10.1007/s11745-001-0770-0 pubmed: 11521963
Carey, M. C. Digestion and absorption of fat. Sem. Gastrointest. Dis. 3, 189–208 (1992).
Caley, L. R. et al. Cystic fibrosis-related gut dysbiosis: a systematic review. Dig. Dis. Sci. 68, 1–18 (2023).
Coffey, M. J. et al. Gut microbiota in children with cystic fibrosis: a taxonomic and functional dysbiosis. Sci. Rep. 9, 1–14 (2019).
doi: 10.1038/s41598-019-55028-7
Marsh, R. G. et al. Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis. J. Cyst. Fibros. 21, 506–513 (2022).
doi: 10.1016/j.jcf.2021.11.014 pubmed: 34895838
Calvo-Lerma, J. et al. Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose. Pediatr. Res. 89, 205–210 (2021).
doi: 10.1038/s41390-020-0860-3 pubmed: 32247283
Roca, M. et al. Fecal calprotectin in healthy children aged 4–16 years. Sci. Rep. 10, 20565 (2020).
doi: 10.1038/s41598-020-77625-7 pubmed: 33239728 pmcid: 7688634
Lluesa, J. H. et al. Lipidic profiles of patients starting peritoneal dialysis suggest an increased cardiovascular risk beyond classical dyslipidemia biomarkers. Sci. Rep. 12, 16394 (2022).
doi: 10.1038/s41598-022-20757-9 pubmed: 36180468 pmcid: 9525574
Chen, S., Zhou, Y., Chen, Y. & Gu, J. Fastp: an Ultra-fast All-In-One FASTQ Preprocessor. Bioinformatics 34, i884–i890 (2018).
doi: 10.1093/bioinformatics/bty560 pubmed: 30423086 pmcid: 6129281
Magoč, T. & Salzberg, S. L. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27, 2957–2963 (2011).
doi: 10.1093/bioinformatics/btr507 pubmed: 21903629 pmcid: 3198573
Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
doi: 10.1038/nmeth.3869 pubmed: 27214047 pmcid: 4927377
Team, R. D. C. A language and environment for statistical computing. http://www.R-project.org . (2009)
McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PloS one 8, e61217 (2013).
doi: 10.1371/journal.pone.0061217 pubmed: 23630581 pmcid: 3632530
. Microbiome R package. URL: http://microbiome.github.io
Gaujoux, R. & Seoighe, C. A flexible R package for nonnegative matrix factorization. BMC Bioinforma. 11, 1–9 (2010).
doi: 10.1186/1471-2105-11-367
Bürkner, P. C. Bayesian item response modeling in R with brms and Stan. arXiv 2020. arXiv preprint arXiv:1905.09501.
Bürkner, P. C. & Charpentier, E. Monotonic effects: A principled approach for including ordinal predictors in regression models. PsyArXiv Preprints. 1-20 (2018).
Wickham, H., Chang, W. & Wickham, M. H. Package ‘ggplot2’. Create elegant data visualisations using the grammar of graphics. Version 2, 1–189 (2016).
Calvo-Lerma, J. et al. Clinical evaluation of an evidence-based method based on food characteristics to adjust pancreatic enzyme supplements dose in cystic fibrosis. J. Cyst. Fibros. 20, e33–e39 (2021).
doi: 10.1016/j.jcf.2020.11.016 pubmed: 33279468
Tso, P., Kendrick, H., Balint, J. A. & Simmonds, W. J. Role of biliary phosphatidylcholine in the absorption and transport of dietary triolein in the rat. Gastroenterology 80, 60–65 (1981).
doi: 10.1016/0016-5085(81)90191-8 pubmed: 6893826
Calvo-Lerma, J., Fornés-Ferrer, V., Heredia, A. & Andrés, A. In vitro digestion models to assess lipolysis: the impact of the simulated conditions of gastric and intestinal pH, bile salts and digestive fluids. Food Res. Int. 125, 108511 (2019).
doi: 10.1016/j.foodres.2019.108511 pubmed: 31554063
Oliphant, K. & Allen-Vercoe, E. Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health. Microbiome 7, 1–15 (2019).
doi: 10.1186/s40168-019-0704-8
Ocvirk, S. & O’Keefe, S. J. Dietary fat, bile acid metabolism and colorectal cancer. Semin. Cancer Biol. 73, 347–355 (2021).
doi: 10.1016/j.semcancer.2020.10.003 pubmed: 33069873
Haasbroek, K., Takabe, W., Yagi, M. & Yonei, Y. High-fat Diet Induced Dysbiosis & Amelioration by Astaxanthin. Med. Sci. 48, 58–66 (2019).
De Weirdt, T. et al. Human faecal microbiota display variable patterns of glycerol metabolism. FEMS Microbiol. Ecol. 74, 601–611 (2010).
doi: 10.1111/j.1574-6941.2010.00974.x pubmed: 20946352
Antosca, K. M. et al. Altered stool microbiota of infants with cystic fibrosis shows a reduction in genera associated with immune programming from birth. J. Bacteriol. 201, e00274–19 (2019).
doi: 10.1128/JB.00274-19 pubmed: 31209076 pmcid: 6657602
Cândido, F. G. et al. Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity. Int. J. Food Sci. Nutr. 69, 125–143 (2018).
doi: 10.1080/09637486.2017.1343286 pubmed: 28675945
Gardiner, B. J. et al. Clinical and microbiological characteristics of Eggerthella lenta bacteremia. J. Clin. Microbiol. 53, 626–635 (2015).
doi: 10.1128/JCM.02926-14 pubmed: 25520446 pmcid: 4298500
King, P. Haemophilus influenzae and the lung (Haemophilus and the lung). Clin. Transl. Med. 1, 1–9 (2012).
doi: 10.1186/2001-1326-1-10
Price, C. E. & O’Toole, G. A. The gut-lung axis in cystic fibrosis. J. Bacteriol. 203, e00311–e00321 (2021).
doi: 10.1128/JB.00311-21 pubmed: 34339302 pmcid: 8459759
Tod, J. & Fine, D. Fecal elastase: a useful test for pancreatic insufficiency? Dig. Dis. Sci. 55, 2709–2711 (2010).
doi: 10.1007/s10620-010-1409-9 pubmed: 20838890
Calvo‐Lerma, J., Fornés‐Ferrer, V., Heredia, A. & Andrés, A. In vitro digestion of lipids in real foods: influence of lipid organization within the food matrix and interactions with nonlipid components. J. Food Sci. 83, 2629–2637 (2018).
doi: 10.1111/1750-3841.14343 pubmed: 30216443 pmcid: 6282792
Kim, M. S., Hwang, S. S., Park, E. J. & Bae, J. W. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ. Microbiol. Rep. 5, 765–775 (2013).
doi: 10.1111/1758-2229.12079 pubmed: 24115628
Dehghan, P., Gargari, B. P. & Jafar-Abadi, M. A. Oligofructose-enriched inulin improves some inflammatory markers and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized controlled clinical trial. Nutrition 30, 418–423 (2014).
doi: 10.1016/j.nut.2013.09.005 pubmed: 24332524
Ng, S. M. & Moore, H. S. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst. Rev. 4, CD003424 (2021).
pubmed: 33905540
van Dorst, J. M., Tam, R. Y. & Ooi, C. Y. What Do We Know about the Microbiome in Cystic Fibrosis? Is There a Role for Probiotics and Prebiotics? Nutrients 14, 480 (2022).
doi: 10.3390/nu14030480 pubmed: 35276841 pmcid: 8840103
Lamichhane, S. et al. Linking gut microbiome and lipid metabolism: moving beyond associations. Metabolites 11, 55 (2021).
doi: 10.3390/metabo11010055 pubmed: 33467644 pmcid: 7830997

Auteurs

Andrea Asensio-Grau (A)

Institute of Food Engineering (FoodUPV). Polytechnic University of València, 46022, València, Spain.
Joint Research Unit NutriCuraPDig, València, Spain.

Miguel Ferriz-Jordán (M)

Institute of Food Engineering (FoodUPV). Polytechnic University of València, 46022, València, Spain.

David Hervás (D)

Department of Statistics (EIO). Polytechnic University of València, 46022, València, Spain.

Ana Heredia (A)

Institute of Food Engineering (FoodUPV). Polytechnic University of València, 46022, València, Spain.
Joint Research Unit NutriCuraPDig, València, Spain.

Jorge García-Hernández (J)

Centre for Advanced Microbiology (CAMA). Polytechnic University of València, 46022, València, Spain.

María Garriga (M)

University Hospital Ramón y Cajal, 28034, Madrid, Spain.

Etna Masip (E)

Health Research Institute La Fe, 46026, València, Spain.

M Carmen Collado (M)

Institute of Agrochemistry and Food Technology. Spanish National Research Council (IATA-CSIC), 46980, València, Spain.

Ana Andrés (A)

Institute of Food Engineering (FoodUPV). Polytechnic University of València, 46022, València, Spain.
Joint Research Unit NutriCuraPDig, València, Spain.

Carmen Ribes-Koninckx (C)

Joint Research Unit NutriCuraPDig, València, Spain.
Health Research Institute La Fe, 46026, València, Spain.

Joaquim Calvo-Lerma (J)

Institute of Food Engineering (FoodUPV). Polytechnic University of València, 46022, València, Spain. joacalle@upv.es.
Joint Research Unit NutriCuraPDig, València, Spain. joacalle@upv.es.
Faculty of Pharmacy and Food Science. University of Valencia, Avda. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain. joacalle@upv.es.

Classifications MeSH