Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

Tungsanga, Somkanya; Udompornpitak, Kanyarat; Worasilchai, Jesadakorn; Ratana-Aneckchai, Tharit; Wannigama, Dhammika Leshan; Katavetin, Pisut; Leelahavanichkul, Asada

doi:10.3390/ijms232415987

Cited by 4 publications

(3 citation statements)

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“…In a previous publication, Candida administration in sham control mice does not induce gut dysbiosis and systemic inflammation, while Candida administration in Bil Nep mice worsens gut dysbiosis and systemic inflammation ( 2 ) similar to our current results. Not only in acute uremia, Candida administration in chronic kidney disease (CKD) in 5/6 nephrectomy mice also induces gut dysbiosis and worsens systemic inflammation through leaky gut-induced endotoxemia and glucanemia that are severe enough to induce fibrosis in several internal organs (kidney, liver, and heart) approximately at 20-week post-surgery ( 12 , 29 ). In this aspect, the presence of gut fungi enhances the severity of uremia-induced systemic inflammation partly through leaky gut-induced endotoxemia and glucanemia which might depend on the abundance of Gram-negative bacteria and fungi, respectively, in the gut.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, impacts of gut fungi, especially C. albicans , in several conditions with leaky gut is not properly considered different from gut bacteria, partly because gut fungi do not seem to cause illness directly. Although we previously demonstrated an impact of oral Candida administration in acute and chronic uremia through bilateral nephrectomy and 5/6 nephrectomy models ( 2 , 12 , 29 , 30 ), respectively, the impact of gut fungi on metabolome analysis has never been described. As such, SCFAs (acetate, propionate, and butyrate) are metabolic products of anaerobic bacterial fermentation, especially on the complex carbohydrates-rich diets, in the intestine that is important for the maintenance of intestinal homeostasis ( 31 – 33 ).…”

Section: Introductionmentioning

confidence: 99%

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Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

Chancharoenthana

Kamolratanakul²,

Visitchanakun³

et al. 2023

Front. Immunol.

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The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily Candida gavage with or without probiotics (different times of administration) for 1 week prior to bilateral nephrectomy (Bil Nep) in 8-week-old C57BL6 mice as the possible models more resemble human conditions were performed. Candida-administered Bil Nep mice demonstrated more severe conditions than Bil Nep alone as indicated by mortality (n = 10/group) and other 48 h parameters (n = 6-8/group), including serum cytokines, leaky gut (FITC-dextran assay, endotoxemia, serum beta-glucan, and loss of Zona-occludens-1), and dysbiosis (increased Enterobacteriaceae with decreased diversity in microbiome analysis) (n = 3/group for fecal microbiome) without the difference in uremia (serum creatinine). With nuclear magnetic resonance metabolome analysis (n = 3-5/group), Bil Nep reduced fecal butyric (and propionic) acid and blood 3-hydroxy butyrate compared with sham and Candida-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, Lacticaseibacillus rhamnosus dfa1 (SCFA-producing Lacticaseibacilli) (n = 8/group) attenuated the model severity (mortality, leaky gut, serum cytokines, and increased fecal butyrate) of Bil Nep mice (n = 6/group) (regardless of Candida). In enterocytes (Caco-2 cells), butyrate attenuated injury induced by indoxyl sulfate (a gut-derived uremic toxin) as indicated by transepithelial electrical resistance, supernatant IL-8, NFκB expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by Candida administration; however, the presence of Candida in the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

Chancharoenthana

Kamolratanakul²,

Visitchanakun³

et al. 2023

Front. Immunol.

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“…Kidney injury scores were determined by tubular cell damage with the scores as previously published [31,32], including, 0; no damage, 1; 0-25% tubular damage, 2; 25-50% tubular damage, 3; 50-75% tubular damage, and 4; 75-100% tubular damage. Liver damage was determined based on inflammation and hepatocyte necrosis with the following scores, including 0 (no finding); 1 (mild); 2 (moderate); and 3 (severe) [25,[33][34][35]. Colon damage scores were evaluated using the Geboes Score (GS) based on the erosions or ulcerations, mononuclear cell infiltration, and structural alterations with scores ranging from 0-5 [36].…”

Section: Histological Analysismentioning

confidence: 99%

Kazachstania pintolopesii in Blood and Intestinal Wall of Macrophage-Depleted Mice with Cecal Ligation and Puncture, the Control of Fungi by Macrophages during Sepsis

Hiengrach,

Chindamporn,

Leelahavanichkul

2023

JoF

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Although macrophage depletion is a possible emerging therapeutic strategy for osteoporosis and melanoma, the lack of macrophage functions can lead to inappropriate microbial control, especially the regulation of intestinal microbiota. Cecal ligation and puncture (CLP) sepsis was performed in regular mice and in mice with clodronate-induced macrophage depletion. Macrophage depletion significantly increased the mortality and severity of sepsis-CLP mice, partly through the increased fecal Ascomycota, especially Kazachstania pintolopesii, with polymicrobialbacteremia (Klebsiella pneumoniae, Enterococcus faecalis, and Acinetobacter radioresistens). Indeed, macrophage depletion with sepsis facilitated gut dysbiosis that directly affected gut permeability as yeast cells were located and hidden in the colon crypts. To determine the interactions of fungal molecules on bacterial abundance, the heat-kill lysate of fungi (K. pintolopesii and C. albicans) and purified (1→3)-β-d-glucan (BG; a major component of the fungal cell wall) were incubated with bacteria that were isolated from the blood of macrophage-depleted mice. There was enhanced cytokine production of enterocytes (Caco-2) after the incubation of the lysate of K. pintolopesii (isolated from sepsis mice), the lysate of C. albicans (extracted from sepsis patients), and BG, together with bacterial lysate. These data support a possible influence of fungi in worsening sepsis severity. In conclusion, macrophage depletion enhanced K. pintolopesii in feces, causing the overgrowth of fecal pathogenic bacteria and inducing a gut permeability defect that additively worsened sepsis severity. Hence, the fecal fungus could be spontaneously elevated and altered in response to macrophage-depleted therapy, which might be associated with sepsis severity.

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The leaky gut and the gut microbiome in sepsis – targets in research and treatment

et al. 2023

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Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1→3)-β-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.

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Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

Cited by 4 publications

References 84 publications

Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

Kazachstania pintolopesii in Blood and Intestinal Wall of Macrophage-Depleted Mice with Cecal Ligation and Puncture, the Control of Fungi by Macrophages during Sepsis

The leaky gut and the gut microbiome in sepsis – targets in research and treatment

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