Diabetes is a major health
concern all over the world, nearly 9% of the worldwide adult population suffers
fromthisdisease. Numerous studies have shownthat AKR1B1is implicated in
diabetescomplications1-3, AKR1B1 can catalyzesorbitol production from glucose,
and induceexcess sorbitolproduction. Sorbitolis difficult to diffuse across the
cell membranes, whichcausesosmotic damage,and finallyleads to diabetic

Here we speculatethat AKR1B8
isalsoimplicated in diabetes(type 2 diabetes).Our lab is now working on the
role of AKR1B8 (an ortholog in human of AKR1B10) in diabetes using AKR1B8
deficient mice, and checked the gut microbiotacomposition.Here we observed
microbiota shifts in AKR1B8deficient micecompare with wild-type mice, we also
observeddecreased total bacterial load and microbiotadiversityin
AKR1B8deficient mice. At phylum level, we observed higher abundance of
Firmicutes, while lower abundance of bacteroidetes. And the ratio of
Firmicutesto bacteroidetesare significantly higher in AKR1B8deficient mice.At
genuslevel, we observed higher abundanceof Prevotella, Akkermansiawhile lower
abundance of Sutterellaand Lactobacillus.

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Microbiota plays a crucial role
in human gastrointestinal health, contributingto the fermentation and
absorption.Microbiotacanalsoregulate the blood glucoseand energy metabolism,and
playsan important role in diabetes 5, 6.Gut microbiota in preclinical type 1 diabetes
mellitus(T1DM)is characterized by Bacteroidetes dominating at the phylum level7. While
clinical studies showed thattype 2 diabetes mellitus (T2DM) patients havean
elevated Firmicutes/Bacteroidetes ratio compared with healthy people8,9. Hereour
preliminary results also showed significant higher Firmicutes/Bacteroidetes
ratio in AKR1B8 deficient mice.The alteration of Firmicutes/Bacteroidetesmay
regulate host energy metabolism through aspecific polysaccharide utilization
loci mechanism 10.

Microbiota can influence the
intestinal permeability and promotemetabolic endotoxin secretion, cause chronic
inflammation, and leading to diabetes 11.Akkermansia muciniphilawas shown to influence
theintestinal mucus and affect intestinal permeability, involvedin the
pathogenesis of insulinresistance 12. Here we also observed significant higher abundance
of Akkermansia muciniphilaspecies in gut microbiota of AKR1B8 deficient
mice, which may indicate that AKR1B8 is implicated in diabetesthrough
regulating the gut microbiota.

Thus, we speculate that the
altered gut microbiota (higher Firmicutes/Bacteroidetes ratio) induced by
AKR1B8 deficiency may contribute to type 2 diabetes.