Abstract
Background
Metabolic inflammation mediated obesity requires bacterial molecules to trigger immune and adipose cells leading to inflammation and adipose depot development. In addition to the well-established gut microbiota dysbiosis, a leaky gut has been identified in patients with obesity and animal models, characterized by the presence of a tissue microbiota in the adipose fat pads.
Methods
To determine its potential role, we sequenced the bacterial 16 S rRNA genes in the visceral adipose depot of patients with obesity. Taking great care (surgical, biochemical, and bioinformatic) to avoid environmental contaminants. We performed statistical discriminant analyses to identify specific signatures and constructed network of interactions between variables.
Results
The data showed that a specific 16SrRNA gene signature was composed of numerous bacterial families discriminating between lean versus patients with obesity and people with severe obesity. The main discriminant families were Burkholderiaceae, Yearsiniaceae, and Xanthomonadaceae, all of which were gram-negative. Interestingly, the Morganellaceae were totally absent from people without obesity while preponderant in all in patients with obesity. To generate hypotheses regarding their potential role, we inferred metabolic pathways from the 16SrRNA gene signatures. We identified several pathways associated with adenosyl-cobalamine previously described to be linked with adipose tissue development. We further identified chorismate biosynthesis, which is involved in aromatic amino-acid metabolism and could play a role in fat pad development. This innovative approach generates novel hypotheses regarding the gut to adipose tissue axis.
Conclusions
This innovative approach generates novel hypotheses regarding the gut to adipose tissue axis in obesity and notably the potential role of tissue microbiota.
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Data availability
MiSeq 16 S rRNA gene sequences were deposited under the primary accession number PRJEB53362 and a secondary number ERP138154 on June 30th 2022.
Change history
08 September 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41366-023-01377-3
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Acknowledgements
We wish to extend our gratitude to the study participants, investigators, monitors and study nurses who enabled this study. We are grateful to Bogdana Dorcioman MD and the corresponding team from the Laboratory Department and Emergency of the Mures County Hospital, who performed blood analysis and who provided some technical help.
Funding
This study was supported by subsides from the Agence Nationale de la Recherche, the Région Midi Pyrénées to R.B. This research program was partly funded as well by VAIOMER SAS (project no. 6869/12.06.2014) through the University of Medicine and Pharmacy Tirgu Mures. This work was supported by EU-FP7 FLORINASH (Health-F2-2009-241913) to RB, MF, JMFR. “This work was supported by the University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș Research Grant number 294/4/14.01.2020”. A subside was allocated to Jiuwen Sun and Alberic Germain from the Fondation Française de Recherche en Diabétologie (FFRD) and from the Société Francophone du Diabète (SFD) and European Foundation for the Study of Diabetes (EF).
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The study was designed by RB, JMFR, RN, and MF. The experiments and analyses were done by JS, GK, and FS. The manuscript was written and data analyzed by JS, AG, RB, FS, BL, MF, JMFR, and AB.
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RB received honorarium from Vaiomer and had shares. BL and FS are employees of Vaiomer. The other authors have no competing interests.
Ethics approval and consent to participate
A monocentric observational study was conducted in the Second Department of Surgery, Emergency Mureş County Hospital of Romania. All research procedures performed in this study were in strict accordance with a pre-defined protocol and adhered to the Good Clinical Practice guidelines and the Declaration of Helsinki. The study was approved by the Coordinating Ethics Committee of the Emergency Mureş County Hospital, Romania (registration 4065/2014): TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver and Adipose Tissue Microbiota, registration 4065/2014. Registered 01 01 2014. All participants provided informed consent prior to participation. The patients who gave their consent to perform an adipose tissue biopsy during the procedure were eligible.
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Sun, J., Germain, A., Kaglan, G. et al. The visceral adipose tissue bacterial microbiota provides a signature of obesity based on inferred metagenomic functions. Int J Obes 47, 1008–1022 (2023). https://doi.org/10.1038/s41366-023-01341-1
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DOI: https://doi.org/10.1038/s41366-023-01341-1