Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

Faucher, Quentin; Jardou, Manon; Brossier, Clarisse; Picard, Nicolas; Marquet, Pierre; Lawson, Roland

doi:10.3389/fendo.2022.898878

Cited by 3 publications

(4 citation statements)

References 94 publications

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“…Enterobacter cloacae is the causative gut bacterium that induces obesity and insulin resistance in animals ( 53 ). The percentage of butyrate-producing bacteria (such as Roseburia and Faecalibacterium prauznitzii ) is significantly reduced in the gut microbiota of patients with T2DM ( 54 ). However, there are increased levels of Lactobacillus and some opportunistic pathogens such as Desulfovibrio sp.…”

Section: Discussionmentioning

confidence: 99%

“…An aberrant gut microbiota composition is highly correlated with obesity and insulin resistance, which play important roles in the onset and development of T2DM (52). Enterobacter cloacae is the causative gut bacterium that induces obesity and insulin resistance in animals (53). The percentage of butyrate-producing bacteria (such as Roseburia and Faecalibacterium prauznitzii) is significantly reduced in the gut microbiota of patients with T2DM (54).…”

Section: Discussionmentioning

confidence: 99%

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Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice

Wang

et al. 2023

Front. Nutr.

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IntroductionThe polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities.MethodsThis study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.ResultsThe results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.DiscussionThis indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice

Wang

et al. 2023

Front. Nutr.

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“…Intestinal dysbiosis-associated with immunosuppressive therapy is a key factor in the pathogenesis of several post-transplant disease[ 69 ].…”

Section: Clinical Implications Of Dysbiosis In Sotsmentioning

confidence: 99%

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Salvadori,

Rosso

2024

World J Transplant

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Gut microbiota is often modified after kidney transplantation. This principally happens in the first period after transplantation. Antibiotics and, most of all, immunosuppressive drugs are the main responsible. The relationship between immunosuppressive drugs and the gut microbiota is bilateral. From one side immunosuppressive drugs modify the gut microbiota, often generating dysbiosis; from the other side microbiota may interfere with the immunosuppressant pharmacokinetics, producing products more or less active with respect to the original drug. These phenomena have influence over the graft outcomes and clinical consequences as rejections, infections, diarrhea may be caused by the dysbiotic condition. Corticosteroids, calcineurin inhibitors such as tacrolimus and cyclosporine, mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known. In contrast is well known how the gut microbiota may interfere with glucocorticoids, which may be transformed into androgens. Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus. The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase, may be transformed into the inactive product.

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“…In fact, the inhibition of the m-TOR pathway was suggested as another mechanism through which TAC induced diabetes [ 50 ]. There has been speculation about a possible link between intestinal dysbiosis and the development of PTDM [ 51 ].…”

Section: Post-transplant Diabetes Mellitusmentioning

confidence: 99%

Nutrition Disturbances and Metabolic Complications in Kidney Transplant Recipients: Etiology, Methods of Assessment and Prevention—A Review

Górska

Kurnatowska

2022

Nutrients

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Nutrition disturbances occur at all stages of chronic kidney disease and progress with the decrease of the kidney filtration rate. Kidney transplantation (KTx) as the best form of kidney replacement therapy poses various nutritional challenges. Prior to transplantation, recipients often present with mild to advanced nutrition disturbances. A functioning allograft not only relieves uremia, acidosis, and electrolyte disturbances, but also resumes other kidney functions such as erythropoietin production and vitamin D3 metabolism. KTx recipients represent a whole spectrum of undernutrition and obesity. Since following transplantation, patients are relieved of most dietary restrictions and appetite disturbances; they resume old nutrition habits that result in weight gain. The immunosuppressive regimen often predisposes them to dyslipidemia, glucose intolerance, and hypertension. Moreover, most recipients present with chronic kidney graft disease at long-term follow-ups, usually in stages G2–G3T. Therefore, the nutritional status of KTx patients requires careful monitoring. Appropriate dietary and lifestyle habits prevent nutrition disturbances and may improve kidney graft function. Despite many nutritional guidelines and recommendations targeted at chronic kidney disease, there are few targeted at KTx recipients. We aimed to provide a brief review of nutrition disturbances and known nutritional recommendations for kidney transplant recipients based on the current literature and dietary trends.

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Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

Cited by 3 publications

References 94 publications

Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice

Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Nutrition Disturbances and Metabolic Complications in Kidney Transplant Recipients: Etiology, Methods of Assessment and Prevention—A Review

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