Intestinal Barrier Function in Chronic Kidney Disease

Meijers, Björn; Farré, Ricard; Dejongh, Sander; Vicario, María; Evenepoel, Pieter

doi:10.3390/toxins10070298

Cited by 87 publications

(61 citation statements)

References 65 publications

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“…Among them, Faecalibacterium and Roseburia produce SCFA and are reduced in ESKD patients, consistent with SCFA insufficiency that is observed in gut dysbiosis [ 49 , 50 , 51 , 52 ]. Of note, we did not assess other factors affecting the blood level of indoxyl sulfate, most notably the function of the gut-blood barrier, which has been reported to be disturbed in CKD subjects [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Yang

Chen

et al. 2021

Cells

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Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

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Section: Discussionmentioning

confidence: 99%

Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Yang

Chen

et al. 2021

Cells

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“…Clinical and experimental studies have shown that intestinal barrier defects have been associated with a wide array of diseases, including both enteral disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) ( Brandtzaeg, 2011 ; Michael et al., 2012 ; Salim and Söderholm, 2015 ), and extra-intestinal disorders such as nonalcoholic fatty liver disease, pancreatitis, and obesity ( Luca et al., 2009 ; Yan et al., 2012 ; Xiong et al., 2018 ). The latest study found that intestinal barrier function decreased in CKD as well ( Alice et al., 2015 ; Briskey et al., 2016 ; Meijers et al., 2018 ). Since the glomerular filtration rate is dramatically reduced in CKD ( Wong et al., 2014 ), the heavy influx of urea from body fluids to the gastrointestinal tract, was firstly hydrolyzed to ammonia and then converted to ammonium hydroxide (NH4OH), leading to increased intestinal pH.…”

Section: Discussionmentioning

confidence: 99%

Rhubarb Enema Improved Colon Mucosal Barrier Injury in 5/6 Nephrectomy Rats May Associate With Gut Microbiota Modification

Deng²,

et al. 2020

Front. Pharmacol.

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Chronic kidney disease (CKD) is often accompanied with colon mucosal barrier damage and gut microbiota disturbance, which strongly associate with up-regulated inflammation and kidney tubulointerstitial fibrosis. However, few interventions could protect the damaged barrier effectively. Rheum palmatum L or rhubarb is a common herbal medicine which is widely used to protect the colon mucosal barrier. In previous studies, we found that rhubarb intervention may reduce renal inflammation and tubulointerstitial fibrosis, via gut microbiota modification. However, whether intestinal barrier function could be improved by rhubarb intervention and the relationship with intestinal flora are still unknown. Therefore, we investigated the effects of rhubarb enema on intestinal barrier, and further analyzed the relationship with gut microbiota in 5/6 nephrectomy rats. Results indicated that rhubarb enema improved the intestinal barrier, regulated gut microbiota dysbiosis, suppressed systemic inflammation, and alleviated renal fibrosis. More specifically, rhubarb enema treatment inhibited the overgrowth of conditional pathogenic gut bacteria, including Akkermansia, Methanosphaera, and Clostridiaceae in CKD. The modification of gut microbiota with rhubarb intervention displayed significant correlation to intestinal barrier markers, TLR4-MyD88-NF-kB inflammatory response, and systemic inflammation. These results revealed that rhubarb enema could restore intestinal barrier by modifying several functional enteric bacteria, which may further explain the renal protection mechanism of the rhubarb enema.

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“…59 Increased intestinal permeability on barrier compromise also results in movement of pathogen-associated molecular patterns (PAMPs) into the blood, 1 which activate the innate immune response. Release of PAMPS has consequences for organs, including brain and kidney, 10,60 but also for liver. 1 The liver and gut are linked through the portal circulation.…”

Section: Disruptions In Intestinal Barrier Function and Liver Diseasementioning

confidence: 99%

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

2020

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Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.

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Intestinal Barrier Function in Chronic Kidney Disease

Cited by 87 publications

References 65 publications

Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Rhubarb Enema Improved Colon Mucosal Barrier Injury in 5/6 Nephrectomy Rats May Associate With Gut Microbiota Modification

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

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