Gut Microbiota Changes by an SGLT2 Inhibitor, Luseogliflozin, Alters Metabolites Compared with Those in a Low Carbohydrate Diet in db/db Mice

Abstract

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study

“…We routinely explained to the patients to continue the original diet and exercise therapy but did not ask them to follow a special diet or exercise intensively after starting luseogliflozin. Luseogliflozin is reported to regulate essential amino acids, short-chain fatty acids, and intestinal bacteria which leads to an increase in skeletal muscle mass [ 33 ]. Therefore, we believe that a significant reduction in skeletal muscle mass might not occur, however, it is important to consider individual differences and carefully evaluate the patients’ body compositions.…”

Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

“…In addition, short-chain fatty acids (SCFAs) have been shown to thicken the mucin layer and strengthen the intestinal barrier by stimulating the release of IL-22 from lymphocytes, which prevents endotoxins and LPS from entering the body [184,185]. Luseogliflozin increased the abundance of Syntrophothermus lipocalidus, family Syntrophomonadaceae, Parabacteroidesdistasonis distasonis, and genus Anaerotignum, which produce SCFAs [186]. Empagliflozin has been associated with an increase in the population of SCFA-producing bacteria and improvements in diabetes and cardiovascular function [187].…”

Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging

“…The specific role of these gut bacterial species in the gut-muscle axis of older individuals is still unknown. However, Parabacteroides distasonis was found as a marker of gut microbiota flexibility in older individuals [ 128 ] and was associated with improvements in muscle mass after a sodium–glucose co-transporter-2 inhibitor treatment in obese mice [ 129 ]. It is also considered an emerging probiotic for its significant anti-inflammatory properties [ 130 , 131 ].…”