Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment

TY - JOUR

T1 - Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment

AU - Ezzamouri, Bouchra

AU - Rosario, Dorines

AU - Bidkhori, Gholamreza

AU - Lee, Sunjae

AU - Uhlen, Mathias

AU - Shoaie, Saeed

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - The human gut microbiome has been associated with several metabolic disorders including type 2 diabetes mellitus. Understanding metabolic changes in the gut microbiome is important to elucidate the role of gut bacteria in regulating host metabolism. Here, we used available metagenomics data from a metformin study, together with genome-scale metabolic modelling of the key bacteria in individual and community-level to investigate the mechanistic role of the gut microbiome in response to metformin. Individual modelling predicted that species that are increased after metformin treatment have higher growth rates in comparison to species that are decreased after metformin treatment. Gut microbial enrichment analysis showed prior to metformin treatment pathways related to the hypoglycemic effect were enriched. Our observations highlight how the key bacterial species after metformin treatment have commensal and competing behavior, and how their cellular metabolism changes due to different nutritional environment. Integrating different diets showed there were specific microbial alterations between different diets. These results show the importance of the nutritional environment and how dietary guidelines may improve drug efficiency through the gut microbiota.

AB - The human gut microbiome has been associated with several metabolic disorders including type 2 diabetes mellitus. Understanding metabolic changes in the gut microbiome is important to elucidate the role of gut bacteria in regulating host metabolism. Here, we used available metagenomics data from a metformin study, together with genome-scale metabolic modelling of the key bacteria in individual and community-level to investigate the mechanistic role of the gut microbiome in response to metformin. Individual modelling predicted that species that are increased after metformin treatment have higher growth rates in comparison to species that are decreased after metformin treatment. Gut microbial enrichment analysis showed prior to metformin treatment pathways related to the hypoglycemic effect were enriched. Our observations highlight how the key bacterial species after metformin treatment have commensal and competing behavior, and how their cellular metabolism changes due to different nutritional environment. Integrating different diets showed there were specific microbial alterations between different diets. These results show the importance of the nutritional environment and how dietary guidelines may improve drug efficiency through the gut microbiota.

UR - https://www.scopus.com/pages/publications/85146732489

U2 - 10.1038/s41540-022-00261-6

DO - 10.1038/s41540-022-00261-6

M3 - Article

C2 - 36681701

AN - SCOPUS:85146732489

SN - 2056-7189

VL - 9

JO - npj Systems Biology and Applications

JF - npj Systems Biology and Applications

IS - 1

M1 - 2

ER -