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Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis

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Abstract

Chronic kidney disease (CKD) represents a growing public health problem associated with loss of kidney function and cardiovascular disease (CVD), the main leading cause of morbidity and mortality in CKD. It is well established that CKD is associated with gut dysbiosis. Over the past few years, there has been a growing interest in studying the composition of the gut microbiota in patients with CKD as well as the mechanisms by which gut dysbiosis contributes to CKD progression, in order to identify possible therapeutic targets to improve the morbidity and survival in CKD. The purpose of this review is to explore the clinical evidence and the mechanisms involved in the gut-kidney crosstalk as well as the possible interventions to restore a normal balance of the gut microbiota in CKD. It is well known that the influence of the gut microbiota on the gut–kidney axis acts in a reciprocal way: on the one hand, CKD significantly modifies the composition and functions of the gut microbiota. On the other hand, gut microbiota is able to manipulate the processes leading to CKD onset and progression through inflammatory, endocrine, and neurologic pathways. Understanding the complex interaction between these two organs (gut microbiota and kidney) may provide novel nephroprotective interventions to prevent the progression of CKD by targeting the gut microbiota. The review is divided into three main sections: evidences from clinical studies about the existence of a gut microbiota dysbiosis in CKD; the complex mechanisms that explain the bidirectional relationship between CKD and gut dysbiosis; and reports regarding the effects of prebiotic, probiotic, and synbiotic supplementation to restore gut microbiota balance in CKD.

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Abbreviations

Ach:

Acetylcholine

AhR:

Aryl hydrocarbon receptor

ANG II:

Angiotensin II

BUN:

Blood urea nitrogen

CFU:

Colony-forming unit

CKD:

Chronic kidney disease

CRP:

C-reactive protein

CVD:

Cardiovascular disease

eGFR:

Estimated glomerular filtration rate

ESRD:

End-stage renal disease

GABA:

γ-aminobutyric acid

GI:

Gastrointestinal

GLP-1:

Glucagon-like peptide 1

GLP-2:

Glucagon-like peptide 2

GFOB:

Glutamine, dietary fiber, oligosaccharide and Bifidobacterium longum strain

GFR:

Glomerular filtration rate

HAM-RS2:

High amylose maize resistant starch

HD:

Hemodialysis

HPA:

Hypothalamic–pituitary–adrenal

IPA:

Indolepropionic acid

IS:

Indoxyl sulfate

IL-6:

Interleukin-6

IL-10:

Interleukin-10

IAA:

Indole-3-acetic acid

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor-κB

OTUs:

Operational taxonomic units

p-CS:

p-cresyl sulfate

PD:

Peritoneal dialysis

PUFAs:

Poly-unsaturated fatty acids

PYY:

Peptide YY

ROS:

Reactive oxygen species

SCFAs:

Short-chain fatty acids

TMAO:

Trimethylamine n-oxidase

TNF-α:

Tumor necrosis factor α

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Funding

This work was supported by grants from the Universidad de Buenos Aires (UBACYT 20020170100621BA (2018–2022) and Sociedad Argentina de Hipertensión Arterial (Stimulus Grant for Research on Hypertension 2019–2020).

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  1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Anatomía e Histología, Buenos Aires, Argentina

    Natalia Lucía Rukavina Mikusic & Marcelo Roberto Choi

  2. CONICET - Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Buenos Aires, Argentina

    Natalia Lucía Rukavina Mikusic

  3. CONICET - Universidad de Buenos Aires, Instituto Alberto C. Taquini de Investigaciones en Medicina Translacional (IATIMET), Buenos Aires, Argentina

    Nicolás Martín Kouyoumdzian & Marcelo Roberto Choi

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  1. Natalia Lucía Rukavina Mikusic
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Rukavina Mikusic, N.L., Kouyoumdzian, N.M. & Choi, M.R. Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis. Pflugers Arch - Eur J Physiol 472, 303–320 (2020). https://doi.org/10.1007/s00424-020-02352-x

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