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

Bastos, Rosana M C; Simplício-Filho, Antônio; Sávio-Silva, Christian; Oliveira, Luiz Felipe Valter de; Cruz, Giuliano Netto Flores; Sousa, Eliza H.; Noronha, Irene L.; Mangueira, Cristóvão Luis Pitangueiras; Quaglierini-Ribeiro, Heloísa; Josefi-Rocha, Gleice R.; Rangel, Érika B.

doi:10.3390/ijms23073842

Cited by 27 publications

(23 citation statements)

References 67 publications

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“…The gut microbiota has a symbiotic relationship with the host, involving energy metabolism, regulating the gut barrier, and maintaining immune responses (7). Many studies have consistently demonstrated (8)(9)(10)(11)(12) that changes in the composition of gut microbiota regulate the development of diabetes by inducing continuous low-grade inflammation and mediating the therapeutic effects of some type 2 diabetes mellitus(T2DM)drugs (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Chen²,

Yang³

et al. 2023

Front. Endocrinol.

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BackgroundThe intestinal microbiota disorder gradually aggravates during the progression of diabetes. Dapagliflozin (DAPA) can improve diabetes and diabetic kidney disease(DKD). However, whether the gut microbiota plays a role in the protection of DAPA for DKD remains unclear.MethodsTo investigate the effects of DAPA on DKD and gut microbiota composition during disease progression, in our study, we performed 16S rRNA gene sequencing on fecal samples from db/m mice (control group), db/db mice (DKD model group), and those treated with DAPA (treat group) at three timepoints of 14weeks\18weeks\22weeks.ResultsWe found that DAPA remarkably prevented weight loss and lowered fasting blood glucose in db/db mice during disease progression, eventually delaying the progression of DKD. Intriguingly, the study strongly suggested that there is gradually aggravated dysbacteriosis and increased bile acid during the development of DKD. More importantly, comparisons of relative abundance at the phylum level and partial least squares-discriminant analysis (PLS-DA) plots roughly reflected that the effect of DAPA on modulating the flora of db/db mice increased with time. Specifically, the relative abundance of the dominant Firmicutes and Bacteroidetes was not meaningfully changed among groups at 14 weeks as previous studies described. Interestingly, they were gradually altered in the treat group compared to the model group with a more protracted intervention of 18 weeks and 22 weeks. Furthermore, the decrease of Lactobacillus and the increase of norank_f:Muribaculaceae could account for the differences at the phylum level observed between the treat group and the model group at 18 weeks and 22 weeks.ConclusionWe firstly found that the protective effect of DAPA on DKD may be related to the dynamic improvement of the gut microbiota over time, possibly associated with the impact of DAPA on the bile acid pool and its antioxidation effect.

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Section: Introductionmentioning

confidence: 99%

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Chen²,

Yang³

et al. 2023

Front. Endocrinol.

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“…Most recently, Bastos, R.M. et al further confirmed the safety and efficacy of FMT as an effective non-pharmacological approach in BTBR ob/ob DKD mice [137].…”

Section: Study Type Disease Models Administration Methods Outcomes Refmentioning

confidence: 87%

Faecal Microbiota Transplantation and Chronic Kidney Disease

et al. 2022

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Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut–kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.

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“…In addition to its beneficial effects in improving T1DM and T2DM, FMT has been shown to alleviate symptoms associated with diabetic kidney disease ( 53 ). For example, FMT treatment improved multiple parameters including amelioration of insulin resistance, prevention of weight gain as well as reduction of tumor necrosis factor-α (TNF-α) and albuminuria in a mouse model.…”

Section: Fecal Microbiota Transplant Effects On Diabetes and Metaboli...mentioning

confidence: 99%

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols

et al. 2022

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Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.

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

Cited by 27 publications

References 67 publications

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Faecal Microbiota Transplantation and Chronic Kidney Disease

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols

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