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The gut microbiome composition is altered in long-standing type 1 diabetes and associates with glycemic control and disease-related complications

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posted on 2022-06-29, 14:28 authored by Julia IP van Heck, Ranko Gacesa, Rinke Stienstra, Jingyuan Fu, Alexandra Zhernakova, Hermie JM Harmsen, Rinse K Weersma, Leo AB Joosten, Cees J Tack

  

Objective: People with type 1 diabetes are at risk of developing micro- and macrovascular complications. Little is known about the gut microbiome in long-standing type 1 diabetes. We explored differences in the gut microbiome of participants with type 1 diabetes compared to healthy controls and associated the gut microbiome with diabetes-related complications.

Research Design and Methods: Microbiome data of 238 participants with type 1 diabetes with an average disease duration of 28 (±15) years were compared to 2937 age-, sex- and BMI-matched individuals. Clinical characteristics and fecal samples were collected and metagenomic shotgun sequencing was performed. Microbial taxonomy was associated with type 1 diabetes–related characteristics and vascular complications.

Results: No significant difference in the α-diversity of the gut microbiome was found between participants with type 1 diabetes and healthy controls. However, 43 bacterial taxa were significantly depleted in type 1 diabetes, while 37 bacterial taxa were significantly enriched. HbA1c and disease duration explained a significant part of variation in the gut microbiome (R2>0.008, FDR<0.05), and HbA1c was significantly associated with the abundance of several microbial species. Additionally, both micro- and macrovascular complications explained a significant part of variation in the gut microbiome (R2>0.0075, FDR<0.05). Nephropathy was strongly associated with several microbial species. Macrovascular complications displayed similar associations to nephropathy.

Conclusion: Our data show that the gut microbiome is altered in people with (long-standing) type 1 diabetes and is associated to glycemic control and diabetes-related complications. Due to the cross-sectional design, the causality of these relationships remains to be determined.

Funding

The work presented in this manuscript was supported by the collaborative TIMID project (LSHM18057-SGF) financed by the PPP allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) to stimulate public–private partnerships and co-financing by health foundations that are part of the SGF. J.F. was supported by the Dutch Heart Foundation IN-CONTROL (CVON2018-27), an ERC Consolidator grant (grant agreement No. 101001678), NWO-VICI grant VI.C.202.022 and the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture and Science of the government of the Netherlands. A.Z. was supported by the Dutch Heart Foundation IN-CONTROL (CVON2018-27), the ERC Starting Grant 715772, NWO-VIDI grant 016.178.056 and the NWO Gravitation grant Exposome-NL (024.004.017).

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