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.
- intestinal permeability
- obesity surgery
- bacterial translocation
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LM and RC contributed equally.
Contributors LM, RC, AC, HH and PK designed the study; LM, RC, AC, MS and PK wrote and edited the manuscript. LM, RC and AC performed all experiments; LM and RC analysed the data; ST and MG performed immunohistochemistry; NM planned and supervised catalysed reporter deposition fluorescence in situ hybridisation (CARD-FISH) protocol, and ST executed CARD-FISH protocol and subsequent analysis; KDD performed real time expression experiments; JF, MvB, S-BH and HH provided bioinformatical expertise, and HH collected patient data; AD and MB were responsible for sample collection.
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).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.