Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes

Costabile, Adele, Corona, Giulia, Sarnsamak, Kittiwadee, Atar-Zwillenberg, Daphna, Yit, Chesda, King, Aileen J., Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756, Barone, Monica, Turroni, Silvia, Brigidi, Patrizia and Hauge-Evans, Astrid C. (2022) Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes. Frontiers in Microbiology, 13. ISSN 1664-302X

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The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells.

Item Type: Article
Additional Information: Funding information: AC, GC, and AH-E received funding toward the work described in this manuscript from Diabetes UK (Early Career Small Grant, BDA: 18/0005802) with DV and AK as named collaborators.
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
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Depositing User: LivePure Connector
Date Deposited: 26 Oct 2022 16:30
Last Modified: 19 Oct 2023 03:28
URI: https://ueaeprints.uea.ac.uk/id/eprint/89367
DOI: 10.3389/fmicb.2022.1004679


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