Journal Article

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

Lampe, Johanna W., Maskarinec, Gertraud, Raquinio, Phyllis, Randolph, Timothy W., Lim, Unhee, Le Marchand, Loïc, Hullar, Meredith A. J., Setiawan, Veronica W., Kristal, Bruce S., Wilkens, Lynne R., Franke, Adrian A.

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abdomen / Actinobacteria / Aged / Analysis / Bacteria / Bacteria - genetics / Biology and Life Sciences / Body fat / C-reactive protein / Cancer therapies / Clinics / Clostridium / Cohort Studies / Community structure / Cross-Sectional Studies / Dextrose / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - microbiology / Diabetes Mellitus, Type 2 - pathology / Diagnosis / Dietary guidelines / Digestive system / Endotoxins / Escherichia / Ethnic factors / Feces - microbiology / Female / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - physiology / Gene sequencing / Genera / Glucose / Gut microbiota / Health aspects / Health care / Health sciences / Humans / Inflammation / Insulin / Intestinal microflora / Laboratories / Lipopolysaccharide-binding protein / Lipopolysaccharides / Male / Medical research / Medicine and Health Sciences / Metformin / Metformin - therapeutic use / Microbiomes / Microbiota / Microbiota (Symbiotic organisms) / Middle Aged / Minority & ethnic groups / Physical Sciences / Population / Prediabetic State - drug therapy / Prediabetic State - microbiology / Prediabetic State - pathology / Preventive medicine / Proteins / Public health / Questionnaires / RNA, Ribosomal, 16S - genetics / rRNA 16S / Shigella / Translocation / Type 2 diabetes / Women