Fermentable fibers induce rapid macro- And micronutrient depletion in Toll-like receptor 5-deficient mice

Rachel M. Golonka, Beng San Yeoh, Yaqi Li, Piu Saha, Ahmed A. Abokor, Xi Cheng, Xia Xiao, Darshan Shimoga Chandrashekar, Sooryanarayana Varambally, David J. Gonzalez, A. Catharine Ross, Matam Vijay-Kumar

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Functional fermentable fibers are considered essential for a healthy diet. Recently, we demonstrated that gut microbiota dysbiotic mice fed an inulin-containing diet (ICD) developed hepatocellular carcinoma (HCC) within 6 mo. In particular, a subset of Toll-like receptor 5-deficient (T5KO) mice prone to HCC exhibited rapid onset of hyperbilirubinemia (HB) and cholemia; these symptoms provide rationale that ICD induces cholestasis. Our objective in the present study was to determine whether inulin-fed T5KO-HB mice exhibit other known consequences of cholestasis, including essential fatty acid and fat-soluble vitamin deficiencies. Here, we measured hepatic fatty acids and serum vitamin A and D levels from wild-type (WT), T5KO low bilirubin (LB) and T5KO-HB mice fed ICD for 4 wk. Additionally, hepatic RNAseq and proteomics were performed to ascertain other metabolic alterations. Compared with WT and T5KOLB, T5KO-HB mice exhibited steatorrhea, i.e., ~50% increase in fecal lipids. This could contribute to the significant reduction of linoleate in hepatic neutral lipids in T5KO-HB mice. Additionally, serum vitamins A and D were ~50% reduced in T5KO-HB mice, which was associated with metabolic compromises. Overall, our study highlights that fermentable fiber-induced cholestasis is further characterized by depletion of macro-and micronutrients.

Original languageEnglish (US)
Pages (from-to)G955-G965
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume318
Issue number5
DOIs
StatePublished - May 2020

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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