Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.
Rosana M C BastosAntônio Simplício-FilhoChristian Sávio-SilvaLuiz Felipe Valter de OliveiraGiuliano N F CruzEliza H SousaIrene L NoronhaCristóvão L P MangueiraHeloísa Quaglierini-RibeiroGleice R Josefi-RochaÉrika B RangelPublished in: International journal of molecular sciences (2022)
Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBR ob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBR ob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.
Keyphrases
- weight gain
- high fat diet induced
- type diabetes
- insulin resistance
- weight loss
- metabolic syndrome
- body mass index
- glycemic control
- end stage renal disease
- birth weight
- chronic kidney disease
- rheumatoid arthritis
- peritoneal dialysis
- randomized controlled trial
- wound healing
- cell therapy
- risk factors
- adipose tissue
- big data
- skeletal muscle
- microbial community
- electronic health record
- physical activity
- antibiotic resistance genes
- oxidative stress
- diabetic rats