Diabetes is a major healthconcern all over the world, nearly 9% of the worldwide adult population suffersfromthisdisease. Numerous studies have shownthat AKR1B1is implicated indiabetescomplications1-3, AKR1B1 can catalyzesorbitol production from glucose,and induceexcess sorbitolproduction. Sorbitolis difficult to diffuse across thecell membranes, whichcausesosmotic damage,and finallyleads to diabeticcomplication4.
Here we speculatethat AKR1B8isalsoimplicated in diabetes(type 2 diabetes).Our lab is now working on therole of AKR1B8 (an ortholog in human of AKR1B10) in diabetes using AKR1B8deficient mice, and checked the gut microbiotacomposition.Here we observedmicrobiota shifts in AKR1B8deficient micecompare with wild-type mice, we alsoobserveddecreased total bacterial load and microbiotadiversityinAKR1B8deficient mice.
At phylum level, we observed higher abundance ofFirmicutes, while lower abundance of bacteroidetes. And the ratio ofFirmicutesto bacteroidetesare significantly higher in AKR1B8deficient mice.Atgenuslevel, we observed higher abundanceof Prevotella, Akkermansiawhile lowerabundance of Sutterellaand Lactobacillus. Microbiota plays a crucial rolein human gastrointestinal health, contributingto the fermentation andabsorption.Microbiotacanalsoregulate the blood glucoseand energy metabolism,andplaysan important role in diabetes 5, 6.Gut microbiota in preclinical type 1 diabetesmellitus(T1DM)is characterized by Bacteroidetes dominating at the phylum level7. Whileclinical studies showed thattype 2 diabetes mellitus (T2DM) patients haveanelevated Firmicutes/Bacteroidetes ratio compared with healthy people8,9.
Hereourpreliminary results also showed significant higher Firmicutes/Bacteroidetesratio in AKR1B8 deficient mice.The alteration of Firmicutes/Bacteroidetesmayregulate host energy metabolism through aspecific polysaccharide utilizationloci mechanism 10. Microbiota can influence theintestinal permeability and promotemetabolic endotoxin secretion, cause chronicinflammation, and leading to diabetes 11.Akkermansia muciniphilawas shown to influencetheintestinal mucus and affect intestinal permeability, involvedin thepathogenesis of insulinresistance 12. Here we also observed significant higher abundanceof Akkermansia muciniphilaspecies in gut microbiota of AKR1B8 deficientmice, which may indicate that AKR1B8 is implicated in diabetesthroughregulating the gut microbiota.Thus, we speculate that thealtered gut microbiota (higher Firmicutes/Bacteroidetes ratio) induced byAKR1B8 deficiency may contribute to type 2 diabetes.