Butyrate attenuated fat gain through gut microbiota modulation in db/db mice following dapagliflozin treatment

• Published in: Scientific reports 2019-12, Vol.9 (1), p.20300-11, Article 20300
• Main Authors: Oh, Tae Jung, Sul, Woo Jun, Oh, Han Na, Lee, Yun-Kyung, Lim, Hye Li, Choi, Sung Hee, Park, Kyong Soo, Jang, Hak Chul
• Format: Article
• Language: English
• Subjects: 631/326/2565/2134; 692/163/2743; Adipose tissue; Adipose Tissue - drug effects; Animals; Benzhydryl Compounds - pharmacology; Body weight; Butyric Acid - pharmacology; Disease Models, Animal; Food intake; Gastrointestinal Microbiome - drug effects; Glucose; Glucose - metabolism; Glucosides - pharmacology; Humanities and Social Sciences; Intestinal microflora; Intestine; Liver - drug effects; Liver - metabolism; Liver - pathology; Mice; Microbiota; multidisciplinary; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; rRNA 16S; Science; Science (multidisciplinary); Sodium; Sodium butyrate; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Streptococcus; Synergistic effect; Tryptophan; Weight Gain
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-56684-5

We investigated the effect of a combination treatment with dapagliflozin (Dapa), a sodium-glucose cotransporter-2 inhibitor and butyrate on weight change in db/db mice. Six-week-old male db/db mice were assigned to four groups: vehicle with normal chow diet (NCD), Dapa with NCD, vehicle with 5% sodium butyrate-supplemented NCD (NaB), or Dapa with 5% NaB. After six weeks of treatment, faecal microbiota composition was analysed by sequencing 16S ribosomal RNA genes. In the vehicle with NaB and Dapa + NaB groups, body weight increase was attenuated, and amount of food intake decreased compared with the vehicle with the NCD group. The Dapa + NaB group gained the least total and abdominal fat from baseline. Intestinal microbiota of this group was characterized by a decrease of the Firmicutes to Bacteroidetes ratio, a decrease of Adlercreutzia and Alistipes , as well as an increase of Streptococcus . In addition, the proportion of Adlercreutzia and Alistipes showed a positive correlation with total fat gain, whereas Streptococcus showed a negative correlation. Inferred metagenome function revealed that tryptophan metabolism was upregulated by NaB treatment. We demonstrated a synergistic effect of Dapa and NaB treatment on adiposity reduction, and this phenomenon might be related to intestinal microbiota alteration.