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Intestinal anti-inflammatory effects of probiotics in DNBS-colitis via modulation of gut microbiota and microRNAs

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Probiotics have been shown to exert beneficial effects in IBD although their exact mechanisms are not completely understood. The aim of the present study was to assess the intestinal anti-inflammatory activity of different probiotics (Lactobacillus fermentum CECT5716, Lactobacillus salivarius CECT5713, Escherichia coli Nissle 1917, Saccharomyces boulardii CNCMI-745 in the dinitrobenzene sulfonic acid (DNBS) model of mouse colitis and correlate it with the modifications of the gut microbiota and the immune response, focusing on miRNA expression.

Methods

The probiotics were daily administered orally for 25 days. On day 19 colitis was induced by rectal installation of DNBS. At the end of the treatment, mice were sacrificed and the colonic damage was assessed biochemically by analysing the expression of different markers involved in the immune response, including miRNAs; and the colonic microbiota by pyrosequencing. Probiotics properties were also evaluated in vitro in different immune cell types (CMT-93 intestinal epithelial cells and bone marrow-derived macrophages), where the expression of different mRNAs and miRNAs was examined.

Results

All the probiotics displayed intestinal anti-inflammatory effects but slightly different, especially regarding miRNAs expression. Likewise, the probiotics ameliorated the colitis-associated dysbiosis, although showing differences in the main bacterial groups affected.

Conclusion

Among the probiotics assayed, Lactobacillus fermentum CECT5716 and Escherichia coli Nissle 1917 appear to present the best intestinal anti-inflammatory effects, being the latter one of the few probiotics with reputed efficacy in human IBD. Therefore, Lactobacillus fermentum CECT5716 could be considered as a complementary nutritional strategy for IBD treatment.

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Abbreviations

ANOVA:

Analysis of variance

AUC:

Area under the curve

BMDM:

Bone marrow-derived macrophages

DAI:

Disease activity index

DMEM:

Dulbecco's Modified Eagle Medium

DNBS:

Dinitrobenzene sulfonic acid

emPCR:

Emulsion-based clonal amplification

Gapdh :

Glyceraldehyde-3-phosphate dehydrogenase

IBD:

Inflammatory bowel disease

iNos :

Inducible nitric oxide synthase

miRNAs:

MicroRNAs

NO:

Nitric oxide

Ocln :

Occluding

RDP:

Ribosomal database project

Snord95:

Small nucleolar RNA, C/D box 95

STAMP:

Statistical analysis of metagenomic profiles

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Acknowledgements

This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (SAF2011-29648 and AGL2015-67995-C3-3-R) with funds from the European Union. A. Rodriguez-Nogales is a postdoctoral fellow of Instituto de Salud Carlos III (Miguel Servet Program); R. Moron is a postdoctoral fellow of Instituto de Salud Carlos III (Rio Hortega Program); T. Vezza is a postdoctoral fellow from Instituto de Investigación Biosanitaria de Granada. The CIBER-EHD and the “Red de Investigación en SIDA” are funded by the Instituto de Salud Carlos III.

Author information

Author notes

  1. Rocío Morón and Alba Rodríguez-Nogales have contributed equally to the supervision of the study.

Authors and Affiliations

  1. CIBER-EHD, Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071, Granada, Spain

    Francesca Algieri, José Garrido-Mesa, Teresa Vezza, María Jesús Rodríguez-Sojo, María Elena Rodríguez-Cabezas, Julio Gálvez & Alba Rodríguez-Nogales

  2. Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), 18012, Granada, Spain

    Teresa Vezza, María Jesús Rodríguez-Sojo, María Elena Rodríguez-Cabezas, Federico García, Julio Gálvez, Rocío Morón & Alba Rodríguez-Nogales

  3. Research Department of Biosearch, 18004, Granada, Spain

    Mónica Olivares

  4. Servicio Microbiología, Hospital Universitario Clínico San Cecilio, 18100, Granada, Spain

    Federico García

  5. Servicio Farmacia Hospitalaria, Hospital Universitario Clínico San Cecilio, 18100, Granada, Spain

    Rocío Morón

  6. Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, 18012, Granada, Spain

    Alba Rodríguez-Nogales

Authors
  1. Francesca Algieri
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  2. José Garrido-Mesa
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  3. Teresa Vezza
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  4. María Jesús Rodríguez-Sojo
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  9. Rocío Morón
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  10. Alba Rodríguez-Nogales
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Contributions

Conceptualization: GG, AR-N and RM; Methodology: FA, JG-M, MJR-S, MER-C, MO and TV; Formal analysis and investigation: FA, JG-M, MJR-S, MER-C, MO and TV; Writing—original draft preparation: RM and AR-N; Writing—review and editing: TV, RM and AR-N; Funding acquisition: JG; Supervision: JG, RM and AR-N.

Corresponding author

Correspondence to Teresa Vezza.

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Conflict of interest

The authors declare that they do not have any competing interests. The funders had no role in the study design, data collection, and analysis.

Ethical approval

All studies were carried out following the ‘Guide for the Care and Use of Laboratory Animals’ as promulgated by the National Institute of Health and the protocols approved by the Ethic Committee of Laboratory Animals of the University of Granada (Spain) (Ref. No. CEEA-2010–286). They were therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Algieri, F., Garrido-Mesa, J., Vezza, T. et al. Intestinal anti-inflammatory effects of probiotics in DNBS-colitis via modulation of gut microbiota and microRNAs. Eur J Nutr 60, 2537–2551 (2021). https://doi.org/10.1007/s00394-020-02441-8

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