AUTHOR=Chancharoenthana Wiwat , Kamolratanakul Supitcha , Visitchanakun Peerapat , Sontidejkul Supistha , Cheibchalard Thanya , Somboonna Naraporn , Settachaimongkon Sarn , Leelahavanichkul Asada 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1131447

DOI=10.3389/fimmu.2023.1131447

ISSN=1664-3224

ABSTRACT=<p>The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily <italic>Candida</italic> 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. <italic>Candida</italic>-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 <italic>Enterobacteriaceae</italic> 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 <italic>Candida</italic>-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, <italic>Lacticaseibacillus rhamnosus</italic> dfa1 (SCFA-producing <italic>Lacticaseibacilli</italic>) (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 <italic>Candida</italic>). 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, <italic>NFκB</italic> expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by <italic>Candida</italic> administration; however, the presence of <italic>Candida</italic> in the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.</p>