Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease

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Bastos, Rosana M. C. ; Simplicio-Filho, Antonio ; Savio-Silva, Christian ; Oliveira, Luiz Felipe, V ; Cruz, Giuliano N. F. ; Sousa, Eliza H. ; Noronha, Irene L. ; Mangueira, Cristovao L. P. ; Quaglierini-Ribeiro, Heloisa ; Josefi-Rocha, Gleice R. ; Rangel, Erika B.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 7, p. 20-pg., 2022-04-01.

Abstract

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 BTBRob/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-alpha (TNF-alpha) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/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. (AU)

• FAPESP's process: 13/19560-6 - C-kit positive cells are kidney-specific stem cells that have regenerative capacity
• Grantee: Érika Bevilaqua Rangel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/23195-2 - Mesenchymal stem cell therapy for halting the progression of acute and chronic kidney injury and in vivo modulate kidney-derived c-Kit stem cells
• Grantee: Érika Bevilaqua Rangel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/26263-6 - Development of a therapy based on mesenchymal stem cells transfected with plasmids containing the HGF and Klotho genes conjugated to nanoparticles aiming the treatment in an animal model of Diabetic Nephropathy
• Grantee: Eliza Higuti Sousa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/18072-9 - Glomerular mesangial cells mitochondrial dynamics alterations in hyperglycemia followed by mesenchymal stem cell therapy
• Grantee: Christian Sávio Silva
• Support Opportunities: Scholarships in Brazil - Master