The alteration of the gut microbiome by immunosuppressive agents used in solid organ transplantation

Gibson, Caitlin M.; Childs‐Kean, Lindsey M.; Naziruddin, Zahra; Howell, Crystal K.

doi:10.1111/tid.13397

Cited by 30 publications

(27 citation statements)

References 27 publications

(51 reference statements)

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“…MMF was able to prevent the development of hypertension in DOCA-salt due to pharmacological inhibition of B and T cell proliferation [17,18]. Recently, it has been described that MMF influences the gut microbiome in renal transplant patients [19][20][21][22] and rodents [23]. Renal transplant recipients suffer from dysbiosis, characterized by lower diversity and loss of butyrate-producing bacteria, more than one year post-transplantation, and the use of MMF correlates to a lower diversity [21].…”

Section: Introductionmentioning

confidence: 99%

Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

et al. 2020

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Microbiota is involved in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzed whether MMF improves dysbiosis in mineralocorticoid-induced hypertension. Male Wistar rats were assigned to three groups: untreated (CTR), deoxycorticosterone acetate (DOCA)-salt, and DOCA treated with MMF for 4 weeks. MMF treatment reduced systolic BP, improved endothelial dysfunction, and reduced oxidative stress and inflammation in aorta. A clear separation in the gut bacterial community between CTR and DOCA groups was found, whereas the cluster belonging to DOCA-MMF group was found to be intermixed. No changes were found at the phylum level among all experimental groups. MMF restored the elevation in lactate-producing bacteria found in DOCA-salt joined to an increase in the acetate-producing bacteria. MMF restored the percentage of anaerobic bacteria in the DOCA-salt group to values similar to control rats. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. This study demonstrates for the first time that MMF reduces gut dysbiosis in DOCA-salt hypertension models. This effect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

et al. 2020

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“…In that study, prednisolone in combination with mycophenolate and tacrolimus increased E. Coli colonization. Serial testing of fecal samples of kidney transplant recipients revealed that compared to those remaining on maintenance corticosteroid, patients with early GC withdrawal had numerically, but not statistically significant, lower Clostridiales and Erysipelotrichales [124] .…”

Section: Gastrointestinal Side Effectsmentioning

confidence: 88%

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

Preprint

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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“…In that study, prednisolone, in combination with mycophenolate and tacrolimus, increased Escherichia coli colonization. Serial testing of fecal samples of kidney transplant recipients revealed that compared to those remaining on maintenance corticosteroid, patients with early GC withdrawal had numerically but not statistically significant lower Clostridiales and Erysipelotrichales [ 124 ].…”

Section: Side Effectsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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The alteration of the gut microbiome by immunosuppressive agents used in solid organ transplantation

Cited by 30 publications

References 27 publications

Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

Current status of glucocorticoid usage in solid organ transplantation

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