Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 1;11(6):1632-1642.
doi: 10.1080/19490976.2020.1778261. Epub 2020 Jun 24.

Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes

Cristina Menni  1 , Jialing Zhu  2 , Caroline I Le Roy  1 , Olatz Mompeo  1 , Kristin Young  3 , Casey M Rebholz  4 , Elizabeth Selvin  4 , Kari E North  3 , Robert P Mohney  5 , Jordana T Bell  1 , Eric Boerwinkle  2   6 , Tim D Spector  1 , Massimo Mangino  1 , Bing Yu  2 , Ana M Valdes  1   7   8
Affiliations

Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes

Cristina Menni et al. Gut Microbes. .

Abstract

Type 2 diabetes (T2D) is associated with reduced gut microbiome diversity, although the cause is unclear. Metabolites generated by gut microbes also appear to be causative factors in T2D. We therefore searched for serum metabolites predictive of gut microbiome diversity in 1018 females from TwinsUK with concurrent metabolomic profiling and microbiome composition. We generated a Microbial Metabolites Diversity (MMD) score of six circulating metabolites that explained over 18% of the variance in microbiome alpha diversity. Moreover, the MMD score was associated with a significantly lower odds of prevalent (OR[95%CI] = 0.22[0.07;0.70], P = .01) and incident T2D (HR[95%CI] = 0.31[0.11,0.90], P = .03). We replicated our results in 1522 individuals from the ARIC study (prevalent T2D: OR[95%CI] = 0.79[0.64,0.96], P = .02, incident T2D: HR[95%CI] = 0.87[0.79,0.95], P = .003). The MMD score mediated 28%[15%,94%] of the total effect of gut microbiome on T2D after adjusting for confounders. Metabolites predicting higher microbiome diversity included 3-phenylpropionate(hydrocinnamate), indolepropionate, cinnamoylglycine and 5-alpha-pregnan-3beta,20 alpha-diol monosulfate(2) of which indolepropionate and phenylpropionate have already been linked to lower incidence of T2D. Metabolites correlating with lower microbial diversity included glutarate and imidazole propionate, of which the latter has been implicated in insulin resistance. Our results suggest that the effect of gut microbiome diversity on T2D is largely mediated by microbial metabolites, which might be modifiable by diet.

Keywords: Microbial metabolites; incident diabetes; microbiome diversity; prevalent diabetes.

PubMed Disclaimer

Conflict of interest statement

RPM is employee of Metabolon, Inc. TDS is co-founder of Zoe Global Ltd. AMV is a consultant for Zoe Global Ltd. All other authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Metabolites trait significantly associated with gut microbiome alpha diversity (Shannon Index) in the discovery and test set of the TwinsUK cohort and in the overall cohort (using inverse variance fixed effect meta-analysis). Analyses adjusted by age, sex, body mass index, family relatedness, and multiple testing. CI indicates confidence interval.
Figure 2.
Figure 2.
Microbial traits (MMD score, alpha diversity, microbial metabolites), T2D and related traits. Each cell of the matrix contains the correlation coefficient between one microbial trait and a metabolic phenotype score and the corresponding P value. The table is color coded by correlation according to the table legend (red for positive and blue for negative correlations). Analyses are adjusted for age and BMI. ObsOTUs = number of observed OTUs, BMI = body mass index, VFAT = visceral fat mass, HOMA2IR = insulin resistance, T2D = type 2 diabetes, MMD = Microbial Metabolites Diversity score, Shannon = Shannon Alpha Diversity Index, Phenylp = 3-phenylpropionate (hydrocinnamate), Imidazolep = imidazole propionate, IPA = indolepropionate, Cinnamoylgl = cinnamoylglycine, Alphapregan = 5alpha-pregnan-3beta,20alpha-diol monosulfate (2).
Figure 3.
Figure 3.
MMD score and risk of (a) prevalent and (b) incident T2D in the TwinsUK (TUK) and ARIC cohorts and results from fixed effect meta-analyses.
See this image and copyright information in PMC

References

    1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377(9765):557–567. doi:10.1016/S0140-6736(10)62037-5. - DOI - PMC - PubMed
    1. Allin KH, Tremaroli V, Caesar R, Jensen BAH, Damgaard MTF, Bahl MI, Licht TR, Hansen TH, Nielsen T, Dantoft TM, et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2018;61(4):810–820. doi:10.1007/s00125-018-4550-1. - DOI - PMC - PubMed
    1. Menni C, Jackson MA, Pallister T, Steves C, Spector T, Valdes A.. Gut microbiome diversity and high fibre intake are related to lower long term weight gain. Int J Obes (Lond). 2017. doi:10.1038/ijo.2017.66. - DOI - PMC - PubMed
    1. Jackson MA, Verdi S, Maxan ME, Shin CM, Zierer J, Bowyer RCE, Martin T, Williams FMK, Menni C, Bell JT, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun. 2018;9(1):2655. doi:10.1038/s41467-018-05184-7. - DOI - PMC - PubMed
    1. Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262–266. doi:10.1038/nature15766. - DOI - PMC - PubMed

Publication types