AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

1st Faculty of Medicine Charles University Prague Czech Republic

Ambis University Department of Economics and Management Prague Czech Republic

Department of Internal Medicine Kralovske Vinohrady University Hospital and 3rd Faculty of Medicine Charles University Prague Czech Republic

Division of Food and Nutrition Science Department of Biology and Biological Engineering Chalmers University of Technology Goteborg Sweden

Faculty of Forestry and Wood Sciences Czech University of Life Sciences Prague Czech Republic

Heidelberg Institute of Global Health Medical Faculty and University Hospital Heidelberg University Heidelberg Germany

Institute for Clinical and Experimental Medicine Prague Czech Republic

Institute of Global Food Security Queen's University Belfast Belfast UK

Institute of Microbiology of the CAS Prague Czech Republic

Mendel University Department of Chemistry and Biochemistry Brno Czech Republic

RECETOX Faculty of Science Masaryk University Brno Czech Republic

000      

00000naa a2200000 a 4500

001      

bmc23011734

003      

CZ-PrNML

005      

20230801133304.0

007      

ta

008      

230718s2023 enk f 000 0|eng||

009      

AR

024    7_

$a 10.1038/s41387-023-00235-5 $2 doi

035    __

$a (PubMed)37085526

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a enk

100    1_

$a Ďásková, N $u First Faculty of Medicine, Charles University, Prague, Czech Republic $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic

245    10

$a Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial / $c N. Ďásková, I. Modos, M. Krbcová, M. Kuzma, H. Pelantová, J. Hradecký, M. Heczková, M. Bratová, P. Videňská, P. Šplíchalová, M. Králová, M. Heniková, J. Potočková, A. Ouřadová, R. Landberg, T. Kühn, M. Cahová, J. Gojda

520    9_

$a AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

650    _2

$a lidé $7 D006801

650    12

$a inulin $x metabolismus $x farmakologie $7 D007444

650    12

$a diabetes mellitus 2. typu $7 D003924

650    _2

$a studie případů a kontrol $7 D016022

650    _2

$a průřezové studie $7 D003430

650    _2

$a multiomika $7 D000095028

650    _2

$a obezita $x metabolismus $7 D009765

650    _2

$a nadváha $x metabolismus $7 D050177

655    _2

$a pozorovací studie $7 D064888

655    _2

$a časopisecké články $7 D016428

655    _2

$a práce podpořená grantem $7 D013485

700    1_

$a Modos, I $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic

700    1_

$a Krbcová, M $u Department of Internal Medicine, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic $1 https://orcid.org/000000017376611X

700    1_

$a Kuzma, M $u Institute of Microbiology of the CAS, Prague, Czech Republic

700    1_

$a Pelantová, H $u Institute of Microbiology of the CAS, Prague, Czech Republic

700    1_

$a Hradecký, J $u Faculty of Forestry and Wood Sciences, Czech University of Life Sciences, Prague, Czech Republic

700    1_

$a Heczková, M $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic

700    1_

$a Bratová, M $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic

700    1_

$a Videňská, P $u Mendel University, Department of Chemistry and Biochemistry, Brno, Czech Republic

700    1_

$a Šplíchalová, P $u RECETOX, Faculty of Science Masaryk University, Brno, Czech Republic

700    1_

$a Králová, M $u Ambis University, Department of Economics and Management, Prague, Czech Republic $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic

700    1_

$a Heniková, M $u Department of Internal Medicine, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic $1 https://orcid.org/0000000232530853

700    1_

$a Potočková, J $u Department of Internal Medicine, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic

700    1_

$a Ouřadová, A $u Department of Internal Medicine, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic

700    1_

$a Landberg, R $u Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Goteborg, Sweden $1 https://orcid.org/0000000263997608

700    1_

$a Kühn, T $u Institute of Global Food Security, Queen's University Belfast, Belfast, UK $u Heidelberg Institute of Global Health (HIGH), Medical Faculty and University Hospital, Heidelberg University, Heidelberg, Germany

700    1_

$a Cahová, M $u Institute for Clinical and Experimental Medicine, Prague, Czech Republic. monika.cahova@ikem.cz $1 https://orcid.org/0000000326405084 $7 xx0070633

700    1_

$a Gojda, J $u Department of Internal Medicine, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic $1 https://orcid.org/0000000279955947

773    0_

$w MED00181736 $t Nutrition & diabetes $x 2044-4052 $g Roč. 13, č. 1 (2023), s. 7

856    41

$u https://pubmed.ncbi.nlm.nih.gov/37085526 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y p $z 0

990    __

$a 20230718 $b ABA008

991    __

$a 20230801133301 $b ABA008

999    __

$a ok $b bmc $g 1963901 $s 1197999

BAS    __

$a 3

BAS    __

$a PreBMC-MEDLINE

BMC    __

$a 2023 $b 13 $c 1 $d 7 $e 20230421 $i 2044-4052 $m Nutrition & diabetes $n Nutr Diabetes $x MED00181736

GRA    __

$a mentorship program supported by Astra Zeneca $p European Foundation for the Study of Diabetes (EFSD)

LZP    __

$a Pubmed-20230718