Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2017; 23(7): 1241-1249
Published online Feb 21, 2017. doi: 10.3748/wjg.v23.i7.1241
Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms
Francesca Romana Ponziani, Maurizio Pompili, Enrico Di Stasio, Maria Assunta Zocco, Antonio Gasbarrini, Roberto Flore
Francesca Romana Ponziani, Maurizio Pompili, Maria Assunta Zocco, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, 00168 Rome, Italy
Enrico Di Stasio, Biochemistry, Agostino Gemelli Hospital, 00168 Rome, Italy
Roberto Flore, Internal Medicine and Vascular Medicine, Agostino Gemelli Hospital, 00168 Rome, Italy
Author contributions: Ponziani FR collected, analyzed data; Ponziani FR and Flore R drafted the paper; Ponziani FR, Pompili M, Zocco MA and Flore R interpreted data; Di Stasio E analyzed blood samples; Pompili M, Zocco MA, Gasbarrini A and Flore R revised the paper; Gasbarrini A and Flore R supervised the study; all authors approved the final version of the paper.
Institutional review board statement: This study was approved by the Local Institutional Review Board.
Informed consent statement: Patients gave their written consent to participate to this study.
Conflict-of-interest statement: The Authors have no conflicts of interest to declare.
Data sharing statement: the anonymous dataset is available from the corresponding author (francesca.ponziani@yahoo.it) and will be provided on request after obtaining all Authors’ agreement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Francesca Romana Ponziani, MD, Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Largo Agostino Gemelli 8, 00168 Rome, Italy. francesca.ponziani@yahoo.it
Telephone: +39-34-71227242 Fax: +39-06-30156265
Received: October 15, 2016
Peer-review started: October 31, 2016
First decision: December 19, 2016
Revised: December 29, 2016
Accepted: January 18, 2017
Article in press: January 18, 2017
Published online: February 21, 2017

To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis.


Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire.


Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls.


SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.

Keywords: Small intestinal bacterial overgrowth, Vitamin K, Dysbiosis, Atherosclerosis, Cardiovascular disease risk

Core tip: The matrix Gla-protein is involved in maintaining vascular health and vitamin K2 is a prerequisite for its activation and function. Intestinal bacteria are the main source of vitamin K2 in humans and small intestinal bacterial overgrowth (SIBO) is associated with altered vitamin K2 metabolism. This study demonstrates that SIBO is associated with increased plasma levels of inactive matrix Gla-protein, which, in turn, correlates directly with early markers of atherosclerotic disease such as increased arterial stiffness. Therefore, SIBO has the potential to serve as an indicator for increased risk of developing an overt cardiovascular disease.