Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury

Emal, Diba; Rampanelli, Elena; Stroo, Ingrid; Butter, Loes M.; Teske, Gwendoline J. D.; Claessen, Nike; Stokman, Geurt; Florquin, Sandrine; Leemans, Jaklien C.; Dessing, Mark C.

doi:10.1681/asn.2016030255

Cited by 105 publications

(82 citation statements)

References 41 publications

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“…Likewise, in a direct comparison, more prevalent monocytic activation was found in patients with acute CRS both with (Group 4) and without consideration of volume state (Group 1) vs. hypertensive controls (Groups 3 and 5). In an animal model of acute kidney injury, a microbiota‐depleted gut was associated with a reduced cellular inflammation within ischaemic kidneys and with a protection against renal ischaemia–reperfusion injury . Conversely, hypervolemia in CHF was found to be associated with increased lipopolysaccharide plasma levels and systemic inflammation .…”

Section: Discussionmentioning

confidence: 97%

Systemic inflammation in acute cardiorenal syndrome: an observational pilot study

et al. 2018

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AimsAcute cardiorenal syndrome (CRS) with and without consideration of the volume state was assessed with regard to inflammatory parameters.Methods and resultsBlood samples from patients with acute CRS (Ronco type 1 or 3, Group 1, n = 15), end‐stage renal disease (Group 2, n = 12), hypertension (Group 3, n = 15), and, in a second cohort, with acute CRS and hypervolemia (Group 4, n = 9) and hypertension (Group 5, n = 10) were analysed with regard to lipopolysaccharide‐binding protein (LBP), interleukins (ILs), and monocyte function (flow cytometry) both on admission (all groups) and on discharge (Groups 1 and 4). By discharge, one Group 1 patient died. LBP (ANOVA for Groups 1–3: P = 0.001) and IL‐6 (Kruskal–Wallis for Groups 1–3: P < 0.0001) were higher in Group 1 (LBP: 11.7 ± 2.0 μg/mL; IL‐6: 15.0 ± 6.1 pg/mL) and in Group 2 (LBP: 10.4 ± 1.4 μg/mL; IL‐6: 14.6 ± 3.8 pg/mL) than in Group 3 (LBP: 5.8 ± 0.4 μg/mL; IL‐6: 1.8 ± 0.4 pg/mL). In a direct comparison, the proportion of activated monocytes (CD14 and CD16 positive) was higher in Group 1 (6.9% ± 0.7%) vs. Group 3 (5.1% ± 0.6%; P = 0.018). Group 4 patients had higher IL‐6 plasma levels (34.2 ± 10.1 pg/mL) than Group 1 patients (15.0 ± 6.1 pg/mL; P = 0.03). All other findings obtained in CRS groups (Groups 1 and 4) were comparable.ConclusionsIn acute CRS, a state of systemic inflammation was found, which is comparable with the end‐stage renal disease situation. In comparison with hypertensive controls, a monocytic activation was found in acute CRS regardless of volume state.

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Section: Discussionmentioning

confidence: 97%

Systemic inflammation in acute cardiorenal syndrome: an observational pilot study

et al. 2018

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“…Specific strains have been found to have effects on immune cells [4], and new insights have been made on overall microbiota effects on systemic immune responses. Gut microbes have now been shown to modulate local intestinal as well as systemic immune responses, with oftentimes surprising associations with distant and diverse organ systems and disease processes such as hematopoiesis [5], brain microglia [6], renal ischemia [7], periodontal disease [8], and graft versus host disease [9]. In this review, we will focus on recent discoveries of how these bacteria interact with the immune system to regulate bone in health and in disease.…”

Section: Introductionmentioning

confidence: 99%

From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone

Hsu

Pacifici

2017

Calcif Tissue Int

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Osteomicrobiology refers to the role of microbiota in bone health and the mechanisms by which the microbiota regulates post-natal skeletal development, bone aging, and pathologic bone loss. Here, we review recent reports linking gut microbiota to changes in bone phenotype. A pro-inflammatory cytokine milieu drives bone resorption in conditions such as sex steroid hormone deficiency. The response of the immune system to activation by the microbiome results in increased circulating osteoclastogenic cytokines in a T cell-dependent mechanism. Additionally, gut microbiota affect bone homeostasis through nutrient absorption, mediation of the IGF-1 pathway, and short chain fatty acid and metabolic products. Manipulation of microbiota through prebiotics or probiotics reduces inflammatory cytokine production, leading to changes in bone density. One mechanism of probiotic action is through upregulating tight junction proteins, increasing the strength of the gut epithelial layer, and leading to less antigen presentation and less activation of intestinal immune cells. Thus, prebiotics or probiotics may represent a future therapeutic avenue for ameliorating the risk of postmenopausal bone loss in humans.

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“…Kidney IRI was induced as described 8. Mice were anesthetized by intraperitoneally injecting sodium pentobarbital (50 mg/kg bodyweight; Sigma‐Aldrich, St. Louis, USA) before surgery, during which both kidneys were exposed through a flank incision and the kidney pedicles were clamped for 30 minutes at 37°C by a heat device.…”

Section: Methodsmentioning

confidence: 99%

Tubular epithelial C1orf54 mediates protection and recovery from acute kidney injury

Xie

Wang

Zhang

et al. 2018

J Cellular Molecular Medi

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Acute kidney injury (AKI) incidence among hospitalized patients is increasing steadily. Despite progress in prevention strategies and support measures, AKI remains correlated with high mortality, particularly among ICU patients, and no effective AKI therapy exists. Here, we investigated the function in kidney ischaemia‐reperfusion injury (IRI) of C1orf54, a newly identified protein encoded by an open reading frame on chromosome 1. C1orf54 expression was high in kidney and low in heart, liver, spleen, lung and skeletal muscle in healthy mice, and in the kidney, C1orf54 was expressed in tubular epithelial cells (TECs), but not in glomeruli. C1orf54 expression was markedly decreased on Day 1 after kidney IRI and then gradually recovered to baseline levels by Day 7. Notably, relative to wild‐type mice, C1orf54‐knockout mice exhibited impaired TEC proliferation and delayed recovery after kidney IRI, which led to deteriorated renal function and increased mortality. Conversely, adenovirus‐mediated C1orf54 overexpression promoted TEC proliferation and ameliorated kidney pathology, which resulted in accelerated renal repair and improved renal function. Mechanistically, C1orf54 was found to promote TEC proliferation through PI3K/AKT signalling. Thus, C1orf54 holds considerable potential as a therapeutic target in kidney IRI.

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Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury

Cited by 105 publications

References 41 publications

Systemic inflammation in acute cardiorenal syndrome: an observational pilot study

Systemic inflammation in acute cardiorenal syndrome: an observational pilot study

From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone

Tubular epithelial C1orf54 mediates protection and recovery from acute kidney injury

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