Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes

Lucas Massier, Rima Chakaroun, Shirin Tabei, Alyce Crane, Konrad David Didt, Jörg Fallmann, Martin Von Bergen, Sven Bastiaan Haange, Henrike Heyne, Michael Stumvoll, Martin Gericke, Arne Dietrich, Matthias Blüher, Niculina Musat, Peter Kovacs*

*Corresponding author for this work
161 Citations (Scopus)

Abstract

Objective Bacterial translocation to various organs including human adipose tissue (AT) due to increased intestinal permeability remains poorly understood. We hypothesised that: (1) bacterial presence is highly tissue specific and (2) related in composition and quantity to immune inflammatory and metabolic burden. Design We quantified and sequenced the bacterial 16S rRNA gene in blood and AT samples (omental, mesenteric and subcutaneous) of 75 subjects with obesity with or without type 2 diabetes (T2D) and used catalysed reporter deposition (CARD) - fluorescence in situ hybridisation (FISH) to detect bacteria in AT. Results Under stringent experimental and bioinformatic control for contaminants, bacterial DNA was detected in blood and omental, subcutaneous and mesenteric AT samples in the range of 0.1 to 5 pg/μg DNA isolate. Moreover, CARD-FISH allowed the detection of living, AT-borne bacteria. Proteobacteria and Firmicutes were the predominant phyla, and bacterial quantity was associated with immune cell infiltration, inflammatory and metabolic parameters in a tissue-specific manner. Bacterial composition differed between subjects with and without T2D and was associated with related clinical measures, including systemic and tissues-specific inflammatory markers. Finally, treatment of adipocytes with bacterial DNA in vitro stimulated the expression of TNFA and IL6. Conclusions Our study provides contaminant aware evidence for the presence of bacteria and bacterial DNA in several ATs in obesity and T2D and suggests an important role of bacteria in initiating and sustaining local AT subclinical inflammation and therefore impacting metabolic sequelae of obesity.

Original languageEnglish
JournalGut
Volume69
Issue number10
Pages (from-to)1796-1806
Number of pages11
ISSN0017-5749
DOIs
Publication statusPublished - 01.10.2020

Funding

Funding This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFg, german research Foundation – Projektnummer 209933838 – sFB 1052; B01, B03 and B09) and from iFB adiposityDiseases (aD2-060e, aD2-06e95 and aD2-K7-117). iFB adiposity Diseases is supported by the Federal Ministry of education and research (BMBF), germany, FKZ: 01eO1501. ProVis is supported by european regional Development Funds (eFre – europe funds saxony).

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