Article Text
PDF
Abstract
Objective To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.
Design We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115T on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice.
Results This newly identified bacterium was detected in 62.7%–69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115T, but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115T administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition.
Conclusions These results suggest that D. welbionis J115T directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.
- obesity
- probiotics
- intestinal microbiology
Data availability statement
Data are available in a public, open access repository. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All datasets and raw data generated and/or analysed during the current study are available from the corresponding author on reasonable request. The 16S rRNA gene sequencing raw sequences of the mouse study can be accessed in Sequence Read Archive database with accession code PRJNA606762. The raw 16S data of the FGFP cohort are available at European Genome-Phenome Archive (https://ega-archive.org/) under accession no. EGAS00001004420, and for the Microbes4U cohort under accession no. EGAS00001003585. For the HMP, healthy human subjects cohort was downloaded from the human microbiome project data portal (https://portal.hmpdacc.org/).
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Data availability statement
Data are available in a public, open access repository. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All datasets and raw data generated and/or analysed during the current study are available from the corresponding author on reasonable request. The 16S rRNA gene sequencing raw sequences of the mouse study can be accessed in Sequence Read Archive database with accession code PRJNA606762. The raw 16S data of the FGFP cohort are available at European Genome-Phenome Archive (https://ega-archive.org/) under accession no. EGAS00001004420, and for the Microbes4U cohort under accession no. EGAS00001003585. For the HMP, healthy human subjects cohort was downloaded from the human microbiome project data portal (https://portal.hmpdacc.org/).
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
TLR and EMdH are joint first authors.
Twitter @matthias_vanhul, @Laure_Bindels, @MicrObesity
Contributors PDC, TLR and EMdH conceived the project. PDC supervised all the preclinical and clinical part. PDC, AE, CDr, CDe, MdB, JPT, AL, DM and MPH contributed to the clinical study Microbes4U. SV, GF and JR contributed to the analysis of the bacterium in the cohort FGFP. RP analysed the human microbiome project and American Gut Project cohort. AP and GGM performed short chain fatty acids measurements. TLR, EMdH, MVH and PDC performed experiments and interpreted all the results. TLR and EMdH generated figures and tables. NMD, LBB, MR and JR contributed to scientific discussions. PDC, TLR, EMdH and MVH wrote the manuscript. All authors discussed the results and approved the manuscript.
Funding This work was supported by the Fonds de la Recherche Scientifique – FNRS-FNRS via the FRFS-WELBIO under grant WELBIO-CR-2017C-02, WELBIO-CR-2019C-02R and Projet de Recherche PDR convention: FNRS T.0030.21. PDC is a recipient of the Funds Baillet Latour (Grant for Medical Research 2015). This work was supported by the Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO) and the Fonds de la Recherche Scientifique – FNRS under EOS Project No. (EOS programme no. 30770923). Funding support for the development of NIH Human Microbiome Project – Core Microbiome Sampling Protocol A (HMP-A) was provided by the NIH Roadmap for Medical Research. Clinical data from this study were jointly produced by the Baylor College of Medicine and the Washington University School of Medicine. Sequencing data were produced by the Baylor College of Medicine Human Genome Sequencing Centre, The Broad Institute, the Genome Centre at Washington University and the J. Craig Ventor Institute. These data were submitted by the EMMES Corporation, which serves as the clinical data collection site for the HMP.
Competing interests PDC is cofounder of A-Mansia biotech. TLR and PDC are inventors on patent applications dealing with the use bacteria in the treatment of obesity and related disorders.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.