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Abstract
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
Here, analyzing data from a six-month clinical trial in pre-diabetes, the authors found 166 of 2,803 measured features, including oral and gut microbiome, metabolites and cytokines, significantly changed in response to dietary interventions; highlighting the microbiome’s role in cardiometabolic health and revealing potential therapeutic avenues.
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Details
; Shilo, Smadar 2
; Godneva, Anastasia 1 ; Ben-Yacov, Orly 1 ; Rein, Michal 1 ; Wolf, Bat Chen 1 ; Lotan-Pompan, Maya 1 ; Bar, Noam 1 ; Weiss, Ervin I. 3
; Houri-Haddad, Yael 4 ; Pilpel, Yitzhak 5 ; Weinberger, Adina 1
; Segal, Eran 1
1 The Weizmann Institute of Science, Department of Computer Science and Applied Mathematics, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563); The Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563)
2 The Weizmann Institute of Science, Department of Computer Science and Applied Mathematics, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563); The Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563); National Center for Childhood Diabetes, Schneider Children’s Medical Center, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petah Tikva, Israel (GRID:grid.414231.1) (ISNI:0000 0004 0575 3167)
3 Tel Aviv University, Goldschleger School of Dental Medicine, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); The Hebrew University-Hadassah School of Dental Medicine, Department of Prosthodontics, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538)
4 The Hebrew University-Hadassah School of Dental Medicine, Department of Prosthodontics, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538)
5 The Weizmann Institute of Science, Department of Molecular Genetics, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563)




