Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery.
Adult
Bacteremia
/ blood
Bariatric Surgery
/ adverse effects
Biomarkers
Body Weight
Computational Biology
/ methods
DNA Contamination
DNA, Bacterial
Diabetes Mellitus, Type 2
/ blood
Female
Glucose
/ metabolism
High-Throughput Nucleotide Sequencing
Humans
In Situ Hybridization, Fluorescence
Male
Metabolic Diseases
/ blood
Metagenome
Metagenomics
/ methods
Microbiota
Middle Aged
Postoperative Period
RNA, Ribosomal, 16S
ROC Curve
Bariatric surgery
Blood bacteria
Metabolic syndrome
Obesity
Type 2 diabetes
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
22 06 2021
22 06 2021
Historique:
received:
07
04
2021
accepted:
02
06
2021
entrez:
23
6
2021
pubmed:
24
6
2021
medline:
17
2
2022
Statut:
epublish
Résumé
The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery. Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH). The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity. We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.
Sections du résumé
BACKGROUND
The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery.
METHODS
Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH).
RESULTS
The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity.
CONCLUSIONS
We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.
Identifiants
pubmed: 34158092
doi: 10.1186/s13073-021-00919-6
pii: 10.1186/s13073-021-00919-6
pmc: PMC8218394
doi:
Substances chimiques
Biomarkers
0
DNA, Bacterial
0
RNA, Ribosomal, 16S
0
Glucose
IY9XDZ35W2
Banques de données
figshare
['10.6084/m9.figshare.12885260', '10.6084/m9.figshare.12876335']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105Références
Nature. 2018 Mar 29;555(7698):623-628
pubmed: 29555994
Nat Methods. 2016 Jul;13(7):581-3
pubmed: 27214047
Microbiome. 2018 Dec 17;6(1):226
pubmed: 30558668
Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6
pubmed: 23193283
J Clin Periodontol. 2006 Jun;33(6):401-7
pubmed: 16677328
Atherosclerosis. 2016 Oct;253:281-344
pubmed: 27594540
J Bacteriol. 1990 Feb;172(2):762-70
pubmed: 1688842
Int J Gen Med. 2014 May 14;7:219-24
pubmed: 24872717
Nat Med. 2017 Jan;23(1):107-113
pubmed: 27892954
Front Microbiol. 2017 Sep 22;8:1765
pubmed: 29018410
Diabetes Care. 2020 Jan;43(Suppl 1):S14-S31
pubmed: 31862745
Nat Med. 2019 Jul;25(7):1096-1103
pubmed: 31263284
Gut. 2018 Aug;67(8):1445-1453
pubmed: 29269438
Nature. 2006 Dec 21;444(7122):1027-31
pubmed: 17183312
Transfusion. 2016 May;56(5):1138-47
pubmed: 26865079
Nucleic Acids Res. 2002 Jul 15;30(14):3059-66
pubmed: 12136088
Diabetes. 2010 Dec;59(12):3049-57
pubmed: 20876719
Transl Psychiatry. 2018 May 10;8(1):96
pubmed: 29743478
Diabetes Care. 2014 Aug;37(8):2343-50
pubmed: 24824547
PLoS One. 2013 Apr 22;8(4):e61217
pubmed: 23630581
J Appl Toxicol. 2021 Feb;41(2):276-290
pubmed: 32725676
Lancet. 2005 Sep 24-30;366(9491):1059-62
pubmed: 16182882
Diabetologia. 2011 Dec;54(12):3055-61
pubmed: 21976140
Nat Rev Microbiol. 2013 Apr;11(4):227-38
pubmed: 23435359
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Metab. 2020 Mar;2(3):233-242
pubmed: 32694777
Elife. 2019 Feb 12;8:
pubmed: 30747106
EMBO Mol Med. 2011 Sep;3(9):559-72
pubmed: 21735552
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6
pubmed: 18936492
PLoS One. 2013 Aug 27;8(8):e71108
pubmed: 24013136
Gut. 2020 Oct;69(10):1796-1806
pubmed: 32317332
Obes Surg. 2017 Oct;27(10):2590-2598
pubmed: 28429171
Nature. 2015 Dec 10;528(7581):262-266
pubmed: 26633628
Nature. 2019 Aug;572(7769):329-334
pubmed: 31367035
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2365-70
pubmed: 19164560
Circulation. 2018 Oct 23;138(17):e426-e483
pubmed: 30354655
Hepatology. 2016 Dec;64(6):2015-2027
pubmed: 27639192
Pharmacogenomics J. 2013 Dec;13(6):514-22
pubmed: 23032991
Diabetes. 2013 Oct;62(10):3341-9
pubmed: 24065795
Front Microbiol. 2019 Jan 17;9:3266
pubmed: 30705670
PLoS One. 2017 Feb 1;12(2):e0169310
pubmed: 28146577
J Clin Lab Anal. 2019 May;33(4):e22842
pubmed: 30714640
Nature. 2012 Oct 4;490(7418):55-60
pubmed: 23023125
Microbiol Immunol. 2008 Jul;52(7):375-82
pubmed: 18667036
J Clin Endocrinol Metab. 2014 Jul;99(7):2575-83
pubmed: 24735424
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Circulation. 2008 Jun 17;117(24):3118-25
pubmed: 18541739
Diseases. 2018 Jun 29;6(3):
pubmed: 29966270
PLoS One. 2013;8(1):e54461
pubmed: 23372728
JAMA. 2002 Dec 4;288(21):2709-16
pubmed: 12460094
Diabetes. 2007 Jul;56(7):1761-72
pubmed: 17456850
Nature. 2020 Mar;579(7800):567-574
pubmed: 32214244
Nucleic Acids Res. 2014 Jan;42(Database issue):D633-42
pubmed: 24288368
Ecology. 2010 Jan;91(1):252-61
pubmed: 20380214
PLoS One. 2010 May 06;5(5):e10507
pubmed: 20463897
Nutrients. 2020 Apr 14;12(4):
pubmed: 32295104
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):590-8
pubmed: 22926153
Methods Enzymol. 2005;397:352-71
pubmed: 16260302
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Nature. 2013 Aug 29;500(7464):541-6
pubmed: 23985870
Nature. 2017 Nov 23;551(7681):507-511
pubmed: 29143816
PLoS One. 2014 Aug 18;9(8):e105221
pubmed: 25133738
Nature. 2011 May 12;473(7346):174-80
pubmed: 21508958
Clin Microbiol Rev. 2009 Jan;22(1):46-64, Table of Contents
pubmed: 19136433
Mol Nutr Food Res. 2020 Aug;64(15):e1900732
pubmed: 31389129
Genome Med. 2016 Jun 15;8(1):67
pubmed: 27306058
Nature. 2013 Aug 29;500(7464):585-8
pubmed: 23985875
Diabetes Care. 2004 Jun;27(6):1487-95
pubmed: 15161807
Genome Med. 2021 Jun 22;13(1):105
pubmed: 34158092
J Clin Microbiol. 2002 Dec;40(12):4771-5
pubmed: 12454193
Int J Obes (Lond). 2013 Nov;37(11):1452-9
pubmed: 23419600
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4592-8
pubmed: 20937873
Nat Biotechnol. 2019 Aug;37(8):852-857
pubmed: 31341288
Gut. 2019 Mar;68(3):578-580
pubmed: 29581241
BMC Biol. 2014 Nov 12;12:87
pubmed: 25387460