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

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 T5KO-LB, 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.NEW & NOTEWORTHY Feeding a dietary, fermentable fiber diet to a subset of Toll-like receptor 5 deficient (T5KO) mice induces early onset hyperbilirubinemia and cholemia that later manifests to hepatocellular carcinoma (HCC). Our study highlights that fermentable fiber-induced cholestasis is characterized with modest macro- and micronutrient deficiencies that may further contribute to hepatic biliary disease. Compared with chemical induction, immunization, surgery, or genetic manipulation, these findings provide a novel approach to study the cholestatic subtype of HCC.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:318

Enthalten in:

American journal of physiology. Gastrointestinal and liver physiology - 318(2020), 5 vom: 01. Mai, Seite G955-G965

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

9005-80-5
Bile Acids and Salts
Bile acids and salts
Cholestasis
Dietary Fiber
Essential fatty acids
Fat-soluble
Inulin
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Tlr5 protein, mouse
Toll-Like Receptor 5
Vitamins

Anmerkungen:

Date Completed 28.07.2020

Date Revised 02.05.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1152/ajpgi.00349.2019

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307869636