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Gut microbiome–short-chain fatty acids interplay in the context of iron deficiency anaemia



Anaemia is a global health concern, with iron deficiency anaemia (IDA) causing approximately 50% of cases. Affecting mostly the elderly, pregnant and adult women and children, physiopathology of IDA in relation to the gut microbiome is poorly understood. Therefore, the objective of this study is to analyse, in an animal model, the effect of IDA on the gut microbiome along the gastrointestinal tract, as well as to relate intestinal dysbiosis to changes in microbial metabolites such as short chain fatty acids (SCFA).


IDA was experimentally induced through an iron deficient diet for a period of 40 days, with twenty weaned male Wistar rats being randomly divided into control or anaemic groups. Blood samples were collected to control haematological parameters, and so were faecal and intestinal content samples to study gut microbial communities and SCFA, using 16S rRNA sequencing and HPLC–UV respectively.


An intestinal dysbiosis was observed as a consequence of IDA, especially towards the distal segments of the gastrointestinal tract and the colon. An increase in SCFA was also noticed during IDA, with the major difference appearing in the colon and correlating with changes in the composition of the gut microbiome. Clostridium_sensu_stricto_1 and Clostridium_sensu_stricto_4 showed the greatest correlation with variations in butyric and propionic concentrations in the colon of anaemic animals.


Composition of intestinal microbial communities was affected by the generation of IDA. An enrichment in certain SCFA-producing genera and SCFA concentrations was found in the colon of anaemic animals, suggesting a trade-off mechanism against disease.

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Data availability

All datasets supporting the conclusions of this article will be made available in the Sequence Read Archive (SRA) of the National Centre for Biotechnology Information (NCBI) upon request. Authors can confirm that all relevant data are included in the article and/or its supplementary information files.

Code availability

Not applicable.


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A.S.L is grateful for the help provided by the PhD programme “Nutrition and Food technology” from the University of Granada. The authors thank Dr Ana Lerma Herrera for her contribution in the development of the animal model. The results presented in this article are part of A.S.L’s doctoral thesis.


This work was financially supported by the local government Junta de Andalucía through research projects (Ref: P11-AGR-7648) and PAIDI research groups (BIO344 and AGR206), and the Ministry of Economy and Competitiveness of Spain co-financed with European Regional Development Funds (Ref: CGL2015-71709-R, PEJ2018-004702-A). This project was supported by Carlos III Health Institute (AC18-00008), under the frame of EuroNanoMed III. A.S.L., M.G.B and V.S.M. were supported by a fellowship from the Ministry of Education, Culture and Sport (FPU 17/05413, FPU 16/05954 and FPU 16/05822). M.O.G acknowledges for the funds received by the F.P.U. fellowship provided by University of Almería.

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Authors and Affiliations



MS, JAGS and ILA developed the original idea, contributed to the design of the study and critically revised the manuscript. A.S.L, M.J.M.A and M.G.B participated in the in vivo model of iron deficiency. VPC, VSM, ALR and MOG did the laboratory analysis and produced the experimental data. A.S.L performed the bioinformatic and statistical analysis and wrote the original draft. MS, JAGS and ILA equally contributed and jointly supervised this work.

Corresponding authors

Correspondence to Miguel Soriano or José Antonio García-Salcedo.

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The authors declare that they have no conflict of interest.

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Experimental procedures described in this study have been performed in accordance with European guidelines (Declaration of Helsinki; Directive 2010/63/EU) and approved by the Ethics Committee of the University of Granada and the local government Junta de Andalucía (ref 06/06/2019/100).

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Soriano-Lerma, A., García-Burgos, M., Alférez, M.J. et al. Gut microbiome–short-chain fatty acids interplay in the context of iron deficiency anaemia. Eur J Nutr 61, 399–412 (2022).

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  • Iron deficiency anaemia
  • Gut microbiome
  • Short-chain fatty acids
  • Intestinal microbial community
  • Microbial metabolites