OBJECTIVES: We sought to establish the effects of 1 mo of intermittent fasting on the gut microbiome.
METHODS: We took advantage of intermittent fasting being voluntarily observed during the Islamic faith-associated Ramadan and sampled feces and blood, as well as collected longitudinal physiologic data in 2 cohorts, sampled in 2 different years. The fecal microbiome was determined by 16S sequencing. Results were contrasted to age- and body weight-matched controls and correlated to physiologic parameters (e.g., body mass and calorie intake).
RESULTS: We observed that Ramadan-associated intermittent fasting increased microbiome diversity and was specifically associated with upregulation of the Clostridiales order-derived Lachnospiraceae [no fasting 24.6 ± 13.67 compared with fasting 39.7 ± 15.9 in relative abundance (%); linear discriminant analysis = 4.9, P
AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1.
MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells.
RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment.
CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.