The gut microbiome and type 2 diabetes status in the Multiethnic Cohort.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2021
Historique:
received: 05 11 2020
accepted: 15 04 2021
entrez: 23 6 2021
pubmed: 24 6 2021
medline: 28 10 2021
Statut: epublish

Résumé

The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP). In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D. T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.

Sections du résumé

BACKGROUND
The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).
METHODS
In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.
RESULTS
Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.
CONCLUSIONS
T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.

Identifiants

pubmed: 34161346
doi: 10.1371/journal.pone.0250855
pii: PONE-D-20-34897
pmc: PMC8221508
doi:

Substances chimiques

RNA, Ribosomal, 16S 0
Metformin 9100L32L2N

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0250855

Subventions

Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL140335
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001855
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000130
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA071789
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Gertraud Maskarinec (G)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Phyllis Raquinio (P)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Bruce S Kristal (BS)

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

Veronica W Setiawan (VW)

Department of Preventive Medicine, University of Southern California, Los Angeles, California, United States of America.

Lynne R Wilkens (LR)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Adrian A Franke (AA)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Unhee Lim (U)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Loïc Le Marchand (L)

Population Sciences in the Pacific, University of Hawai'i Cancer Center, Honolulu, Hawaii, United States of America.

Timothy W Randolph (TW)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Johanna W Lampe (JW)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Meredith A J Hullar (MAJ)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

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Classifications MeSH