Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile

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  • dc.contributor.author Arnoriaga Rodríguez, María
  • dc.contributor.author Mayneris Perxachs, Jordi
  • dc.contributor.author Burokas, Aurelijus, 1982-
  • dc.contributor.author Pérez Brocal, Vicente
  • dc.contributor.author Moya, Andrés
  • dc.contributor.author Portero Otín, Manuel
  • dc.contributor.author Ricart, Wifredo
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.contributor.author Fernández Real, Jose M.
  • dc.date.accessioned 2020-06-04T06:23:16Z
  • dc.date.available 2020-06-04T06:23:16Z
  • dc.date.issued 2020
  • dc.description.abstract Background: The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans. Results: Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10-2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor's body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10-7), Rikenellaceae (r = 0.702, p = 3.9 × 10-4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = - 0.445, p = 0.038) and Prevotellaceae RA (r = - 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice' weight gain and positively with gut bacterial ClpB-like gene function. Conclusions: In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice. Video Abstract.
  • dc.description.sponsorship This work was partially supported by research grants FIS (PI15/01934) from the Instituto de Salud Carlos III from Spain, SAF2015-65878-R from Ministry of Economy and Competitiveness, Prometeo/2018/A/133 from Generalitat Valenciana, Spain and also by Fondo Europeo de Desarrollo Regional (FEDER) funds, European Commission (FP7, NeuroPain #2013-602891), the Catalan Government (AGAUR, #SGR2017-669, ICREA Academia Award 2015), the Instituto de Salud Carlos III (RTA, #RD16/0017/0020), and the European Regional Development Fund (No. 01.2.2-LMT-K-718-02-0014). María Arnoriaga-Rodríguez is funded by Instituto de Salud Carlos III, Río Hortega (CP19/00190). Jordi Mayneris-Perxachs is funded by Instituto de Salud Carlos III, Miguel Servet (CP18/00009). The project has also been 65% cofinanced by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014-2020). POCTEFA aims to reinforce the economic and social integration of the French–Spanish–Andorran border. Its support is focused on developing economic, social and environmental cross-border activities through joint strategies favouring sustainable territorial development.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, Pérez-Brocal V, Moya A, Portero-Otin M, Ricart W, Maldonado R, Fernández-Real JM. Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile. Microbiome. 2020; 8(1):59. DOI: 10.1186/s40168-020-00837-6
  • dc.identifier.doi http://dx.doi.org/10.1186/s40168-020-00837-6
  • dc.identifier.issn 2049-2618
  • dc.identifier.uri http://hdl.handle.net/10230/44892
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Microbiome. 2020; 8(1):59
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602891
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-65878-R
  • dc.rights © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data ma
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Bacterial gene function
  • dc.subject.keyword Body weight regulation
  • dc.subject.keyword Microbiome
  • dc.subject.keyword Obesity
  • dc.title Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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