Diet-independent correlations between bacteria and dysfunction of gut, adipose tissue, and liver: A comprehensive microbiota analysis in feces and mucosa of the ileum and colon in obese mice with NAFLD

Eveline Gart*, Everton Souto Lima, Frank Schuren, Christa G.F. de Ruiter, Joline Attema, Lars Verschuren, Jaap Keijer, Kanita Salic, Martine C. Morrison, Robert Kleemann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−.Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.

Original languageEnglish
Article number1
JournalInternational Journal of Molecular Sciences
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Adipose tissue inflammation
  • Gut permeability
  • Liver
  • Non-alcoholic fatty liver disease
  • Obesity
  • Short-chain fatty acids

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