Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 14 print issues and online access
$259.00 per year
only $18.50 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
All data generated or analysed during this study are available from the corresponding author on reasonable request. The Illumina sequencing raw data was uploaded to the NCBI database (Submission: ERA23351972, on 15-05-2023) with project reference PRJEB62140, and accession number 326f56c0-a122-4805-94fd-75fc6e881792.
References
Stephenson, A. L. et al. Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study. Am. J. C. l Nut. 97, 872–877 (2013).
Humbert, L. et al. Postprandial bile acid levels in intestine and plasma reveal alteredbiliary circulation in chronic pancreatitis patients. J. Lipid Res. 59, 2202–2213 (2018).
Dorsey, J. & Gonska, T. Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine. J. Cyst. Fibros. 16, S14–S23 (2017).
Coffey, M. J. et al. Gut microbiota in children with cystic fibrosis: a taxonomic and functional dysbiosis. Sci. Rep. 9, 1–14 (2019).
Thavamani, A., Salem, I., Sferra, T. J. & Sankararaman, S. Impact of altered gut Microbiota and its metabolites in cystic fibrosis. Metabolites 11, 123 (2021).
Manor, O. et al. Metagenomic evidence for taxonomic dysbiosis and functional imbalance in the gastrointestinal tracts of children with cystic fibrosis. Sci. Rep. 6, 22493 (2016).
Burke, D. G. et al. The altered gut microbiota in adults with cystic fibrosis. BMC Microb. 17, 1–11 (2017).
Hoffman, L. R. et al. Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis. Clin. Infect. Dis. 58, 396–399 (2014).
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. Res. 201, e00274–19 (2019).
Caley, L. R. et al. Cystic Fibrosis-Related Gut Dysbiosis: A Systematic Review. Dig. Dis. Sci. 68, 1797–1814 (2023).
Kristensen, M. et al. Development of the gut microbiota in early life: The impact of cystic fbrosis and antibiotic treatment. J. Cyst. Fibros. 19, 553–561 (2020).
Miragoli, F. et al. Impact of cystic fbrosis disease on archaea and bacteria composition of gut microbiota. FEMS Microbiol. Ecol. 93, 230 (2017).
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).
Skórka, A., Pieścik-Lech, M., Kołodziej, M. & Szajewska, H. Infant formulae supplemented with prebiotics: Are they better than unsupplemented formulae? An updated systematic review. Br. J. Nutr. 119, 810–825 (2018).
Wang, Y. et al. Opportunistic bacteria confer the ability to ferment prebiotic starch in the adult cystic fibrosis gut. Gut Microbes 10, 367–381 (2019).
Van den Abbeele, P. et al. Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and Clostridium cluster IX. Appl. Environ. Microbiol. 76, 5237–5246 (2010).
Bianchi, F. et al. Modulation of gut microbiota from obese individuals by in vitro fermentation of citrus pectin in combination with Bifidobacterium longum BB-46. Appl. Microbiol. Biotechnol. 102, 8827–8840 (2018).
Schmieder, R., & Edwards, R. Fast identification and removal of sequence contamination from genomic and metagenomic datasets. PloS One. 3, e17288 (2011).
Zheng, X. et al. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids. Metabolomics 9, 818–827 (2013).
Huang, Z., Boekhorst, J., Fogliano, V., Capuano, E. & Wells, J. M. Distinct effects of fiber and colon segment on microbiota-derived indoles and short-chain fatty acids. Food Chem. 398, 133801 (2023).
Duytschaever, G. et al. Cross-sectional and longitudinal comparisons of the predominant fecal microbiota compositions of a group of pediatric patients with cystic fibrosis and their healthy siblings. Appl. Environ. Microbiol. 77, 8015–8024 (2011).
Zemanick, E. T. et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur. Respir. J. 50, 1700832 (2017).
Anand, S. & Mande, S. S. Diet, microbiota and gut-lung connection. Front. Microbiol. 9, 2147 (2018).
Malinen, E. et al. Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am. J. Gastroenterol. 100, 373–382 (2005).
Price, C. E. & O’Toole, G. A. The gut-lung axis in cystic fibrosis. J. Bacteriol. 203, e00311–e00321 (2021).
Madan, J. C. et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: Interaction between intestinal and respiratory tracts and impact of nutritional exposures. mBio 3, e00251–12 (2012).
Bacci, G. et al. Lung and gut microbiota changes associated with pseudomonas aeruginosa infection in mouse models of cystic fibrosis. Int. J. Mol. Sci. 22, 12169 (2021).
Roy, D. Fecal microbiota and probiotic yogurt intake. In: Yogurt in Health and Disease Prevention. 237–258. (Academic Press, 2017).
Akhtar, M. et al. Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation. Anim Nutr. 8, 350–360 (2021).
Collado, M. C., Derrien, M., Isolauri, E., de Vos, W. M. & Salminen, S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Environ. Microbiol. 73, 7767–7770 (2007).
Jakobsdottir, G., Xu, J., Molin, G., Ahrné, S. & Nyman, M. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS One 8, e80476 (2013).
Sarbini, S. R., Kolida, S., Gibson, G. R. & Rastall, R. A. In vitro fermentation of commercial α-gluco-oligosaccharide by faecal microbiota from lean and obese human subjects. Br. J. Nutr. 109, 1980–1989 (2013).
Needham, B., Avolio, J., Young, K., Surette, M. G. & Gonska, T. Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation. Sci. Rep. 8, 1–8 (2018).
Rastall, R. A. & Gibson, G. R. Recent developments in prebiotics to selectively impact beneficial microbes and promote intestinal health. Curr. Opin. Biotechnol. 32, 42–46 (2015).
Hiippala, K. et al. The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Nutrients 10, 988 (2018).
Nogacka, A. M. et al. In vitro evaluation of different prebiotics on the modulation of gut microbiota composition and function in morbid obese and normal-weight subjects. Int. J. Mol. Sci. 21, 906 (2020).
Gough, E. K. et al. Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome 3, 1–10 (2015).
Marsh, R. et al. Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis. J. Cyst. Fibros. 21, 506–513 (2022).
Nielsen, S. et al. Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis. Sci. Rep. 6, 1–11 (2016).
Sánchez-Calvo, J. M. et al. Gut microbiota composition in cystic fibrosis patients: molecular approach and classical culture. J. Cyst. Fibros. 7, S50 (2008).
Li, L. & Somerset, S. The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clin. Nutr. 33, 571–580 (2014).
Cremon, C., Barbaro, M. R., Ventura, M. & Barbara, G. Pre-and probiotic overview. Curr. Opin. Pharmacol. 43, 87–92 (2018).
You, S. et al. The promotion mechanism of prebiotics for probiotics: A review. Front. Nutr. 9, 1000517 (2022).
Asensio-Grau, A. et al. Effect of Lactobacillaceae Probiotics on Colonic Microbiota and Metabolite Production in Cystic Fibrosis: A Comparative In Vitro Study. Nutrients 15, 3846 (2023).
Duque, A. L. R. F. et al. Effect of probiotic, prebiotic, and synbiotic on the gut microbiota of autistic children using an in vitro gut microbiome model. Food Res. Int. 149, 110657 (2021).
He, X. et al. Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial. Sci. Rep. 9, 11589 (2019).
Davila, A.-M. et al. Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. Pharm. Res 68, 95–107 (2013).
Salgaço, M. K. et al. Probiotic infant cereal improves children’s gut microbiota: Insights using the Simulator of Human Intestinal Microbial Ecosystem (SHIME®). Food Res. Int. 143, 110292 (2021).
Wang, S. P. et al. Pivotal roles for pH, lactate, and lactate-utilizing bacteria in the stability of a human colonic microbial ecosystem. MSystems. 5, 10–1128 (2020).
Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006).
Louis, P., Young, P., Holtrop, G. & Flint, H. J. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA: Acetate CoA-transferase gene. Environ. Microbiol. 12, 304–314 (2010).
Van den Bogert, B. et al. Diversity of human small intestinal Streptococcus and Veillonella populations. FEMS Microbiol. Ecol. 85, 376–388 (2013).
Morrison, D. J. & Preston, T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Micro. 7, 189–200 (2016).
Acknowledgements
We thank the children and their families who were involved in the study and Veronica Ballester, the nurse of the paediatric CF unit of Hospital La Fe. RCB would like to acknowledge the support from Generalitat-Valenciana for the grant Plan GenT project (CDEIGENT 2020). JCL acknowledge the Juan de la Cierva Formación Post-doctoral contract awarded by the Spanish Ministry of Science and Innovation (FJC2019-041730-I). AAG would like also to thank the Post-doctoral contract awarded by the Universitat Politècnica de València (PAID-01-21). IATA-CSIC is a Centre of Excellence Severo Ochoa (CEX2021-001189-S MCIN/AEI / 10.13039/ 501100011033). This project was funded by “Programa INBIO 2021” with reference PEDIMIC/AP2021-22 and “Ayuda para potenciar la investigación postdoctoral de la UPV” with reference PAIDPD-22.
Author information
Authors and Affiliations
Contributions
AAG, AH, JGH, MCC, CRK, AA and JCL conceived and designed research. AAG, AH and JGH conducted experiments. RCR and MCC contributed new reagents or analytical tools. EM and CRK provided the faecal samples and resources. AAG, JCL and RCR analysed data. AAG and JCL wrote the manuscript. All authors read and approved the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics approval
This study was approved by the Ethics committees of University Hospital La Fe (Valencia, Spain) (Ref. 2021-111-1) and Universitat Politècnica de València (Valencia, Spain) (Ref. P09_24_11_2021), and perfomerd in accordance with de Declaration of Helinski.
Informed consent
Inform consent was obtained from the participating individual’s guardian.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Asensio-Grau, A., Heredia, A., García-Hernández, J. et al. Effect of beta-glucan supplementation on cystic fibrosis colonic microbiota: an in vitro study. Pediatr Res (2023). https://doi.org/10.1038/s41390-023-02944-0
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41390-023-02944-0