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Lactobacillus stress protein GroEL prevents colonic inflammation

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Abstract

Background

We previously showed that supernatants of Lactobacillus biofilms induced an anti-inflammatory response by affecting the secretion of macrophage-derived cytokines, which was abrogated upon immunodepletion of the stress protein GroEL.

Methods

We purified GroEL from L. reuteri and analysed its anti-inflammatory properties in vitro in human macrophages isolated from buffy coats, ex vivo in explants from human biopsies and in vivo in a mouse model of DSS induced intestinal inflammation. As a control, we used GroEL purified (LPS-free) from E. coli.

Results

We found that L. reuteri GroEL (but not E. coli GroEL) inhibited pro-inflammatory M1-like macrophages markers, and favored M2-like markers. Consequently, L. reuteri GroEL inhibited pro-inflammatory cytokines (TNFα, IL-1β, IFNγ) while favouring an anti-inflammatory secretome. In colon tissues from human biopsies, L. reuteri GroEL was also able to decrease markers of inflammation and apoptosis (caspase 3) induced by LPS. In mice, we found that rectal administration of L. reuteri GroEL (but not E. coli GroEL) inhibited all signs of haemorrhagic colitis induced by DSS including intestinal mucosa degradation, rectal bleeding and weight loss. It also decreased intestinal production of inflammatory cytokines (such as IFNγ) while increasing anti-inflammatory IL-10 and IL-13. These effects were suppressed when animals were immunodepleted in macrophages. From a mechanistic point of view, the effect of L. reuteri GroEL seemed to involve TLR4, since it was lost in TRL4−/− mice, and the activation of a non-canonical TLR4 pathway.

Conclusions

L. reuteri GroEL, by affecting macrophage inflammatory features, deserves to be explored as an alternative to probiotics.

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Acknowledgments

This work was funded by the “Ligue National contre le Cancer”, the “Fondation pour la Recherche Médicale” FDT20170436927 and by a French Government grant managed by the French National Research Agency under the program “Investissements d’Avenir” with reference ANR-11-LABX-0021 (LabEX LipSTIC), ANR-15-IDE and ANR-15-IDE-0003 (I-SITE-BFC). We thank the ”Conseil Regional de Bourgogne-Franche Comté” and the European Union program FEDER for their financial support, and "Cellimap Dijon" and the “Plateforme de cytométrie Dijon” for technical support.

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Author notes

  1. Frédéric Lirussi and Carmen Garrido contributed to the co-direction of the work.

Authors and Affiliations

  1. INSERM, UMR 1231, Laboratoire d’Excellence LipSTIC and « Equipe labellisée par la Ligue Nationale Contre Le Cancer », 7 boulevard Jeanne d’Arc, 21079, Dijon, France

    Alexandre M. M. Dias, Romain Douhard, François Hermetet, Mathilde Regimbeau, Tatiana E. Lopez, Daniel Gonzalez, Sophie Masson, Guillaume Marcion, Killian Chaumonnot, Burhan Uyanik, Sébastien Z. Causse, Tarik Hadi, Christelle Basset, Johanna Chluba, Jacques Grober, Pablo Ortega-Deballon, Oleg N. Demidov, Frédéric Lirussi & Carmen Garrido

  2. Faculty of Medicine and Pharmacy, Université de Bourgogne Franche-Comté, Dijon, France

    Alexandre M. M. Dias, Romain Douhard, François Hermetet, Mathilde Regimbeau, Tatiana E. Lopez, Daniel Gonzalez, Sophie Masson, Guillaume Marcion, Killian Chaumonnot, Burhan Uyanik, Sébastien Z. Causse, Tarik Hadi, Christelle Basset, Johanna Chluba, Jacques Grober, Fabrice Neiers, Pablo Ortega-Deballon, Oleg N. Demidov, Frédéric Lirussi & Carmen Garrido

  3. UMR PAM A 02.102, Dijon, France

    Aurélie Rieu & Jean Guzzo

  4. Centre des Sciences du Goût et de l’Alimentation, INRA, CNRS, Dijon, France

    Fabrice Neiers

  5. Institute of Cytology, RAS, St. Petersburg, Russia

    Oleg N. Demidov

  6. Centre Hospitalier Universitaire, Dijon, France

    Pablo Ortega-Deballon & Frédéric Lirussi

  7. Anticancer Centre Georges-François Leclerc (CGFL), Dijon, France

    Carmen Garrido

Authors
  1. Alexandre M. M. Dias
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  2. Romain Douhard
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Correspondence to Carmen Garrido.

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Dias, A.M.M., Douhard, R., Hermetet, F. et al. Lactobacillus stress protein GroEL prevents colonic inflammation. J Gastroenterol 56, 442–455 (2021). https://doi.org/10.1007/s00535-021-01774-3

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