Attenuated Fecal Dysbiosis and Metabolome Changes in -administered Bilateral Nephrectomy Mice

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Mar 27

PMID 36969207

Authors

Wiwat Chancharoenthana

Supitcha Kamolratanakul

Peerapat Visitchanakun

Supistha Sontidejkul

Thanya Cheibchalard

Naraporn Somboonna

Sarn Settachaimongkon

Asada Leelahavanichkul

Affiliations

Soon will be listed here.

Abstract

The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily 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. -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 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 -Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, dfa1 (SCFA-producing ) (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 ). 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, expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by administration; however, the presence of 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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