Magnhild Eide Macpherson, Norway

Oslo University Hospital Rikshospitalet Research Institute of Internal Medicine

Presenter Of 1 Presentation

Poster Display Autoinflammation

THE GUT MICROBIOTA-DEPENDENT METABOLITE TRIMETHYLAMINE N-OXIDE (TMAO) LINKED TO INFLAMMATION IN CVID

Lecture Time
10:05 - 10:06
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
7
Presentation Topic
Autoinflammation

Abstract

Background and Aims

In addition to recurrent infections, the majority of common variable immunodeficiency (CVID) patients have inflammatory and autoimmune manifestations of unknown etiology. We have previously shown that gut microbial dysbiosis, including increased levels of Gammaproteobacteria, is associated with systemic inflammation in CVID. The gut microbial dependent systemic metabolite trimethylamine N-oxide (TMAO) has been related to systemic inflammation in other diseases. We hypothesized that TMAO through the gut-microbial axis could contribute to systemic inflammation in CVID.

Methods

We measured plasma levels of TMAO and inflammatory markers in 104 CVID patients and 30 healthy controls. In addition, we related TMAO levels to our previous data on gut microbial composition and obtained a dietary questionnaire from 40 CVID patients.

Results

CVID patients had higher plasma levels of TMAO than controls (p=0.021). TMAO correlated positively with the prototypic inflammatory cytokines TNF (p=0.008, rho=0.259) and IL-12 (p=0.012, rho=0.245) known to be involved in the pathogenesis of CVID-related autoimmune complications. Furthermore, gut microbial abundance of Gammaproteobacteria in CVID patients correlated positively with TMAO levels (p=0.021, rho=0.363). Finally, the use of table sugar was associated with elevated TMAO levels (p=0.006, rho=0.437), whereas wine consumption correlated negatively with TMAO levels (p=0.023, rho=-0.369).

Conclusions

CVID patients have increased plasma levels of the gut microbiota-dependent metabolite TMAO associated with increased inflammatory markers and an abundance of the TMA producing Gammaproteobacteria in the gut. TMAO appears linked to systemic inflammation in CVID through the gut microbial axis, which could potentially be modified by diet.

tmao_cvid_inflammation esid2019.jpg

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