A research team from New York found a positive correlation between H. pylori status, increasing age, body mass index and glycated hemoglobin (HbA1c) levels (Chen 2012). That is to say elevated levels of HbA1c and H. pylori were more prevalent in patients with higher BMI and increased age. The was no association between H. pylori and HbA1c levels in individuals under 18 years of age.
…H. pylori positivity was significantly associated with higher mean levels of HbA1c among those with no history of diabetes who had a higher BMI.” Chen et al 2012
What is the mechanism of H. pylori mediated insulin resistance?
This is the conundrum! The presence of H. pylori is associated with reduced Treg cells and imbalanced T helper subsets along with increased activation of innate-immune inflammatory pathways that to disrupt metabolic homeostasis though several mechanisms ( see Kim 2011). Additionally, H. pylori-induced inflammation negatively influences several incretin hormones, namely ghrelin and leptin, both of which regulate appetite, satiety, insulin sensitivity and energy utilization, among others.
…our study provides further evidence that H. pylori affects host metabolic status.” notes Kim et al 2011
Can eradication of H. pylori influence metabolic status?
Based upon the above one would think yes. However in 2011 Francois et al conducted a study involving 92 subjects- 44 H. pylori positive and 38 negative controls- and assessed the effect of H. pylori eradication on the appetite hormones (discussed previously here) ghrelin, leptin, GIP, PYY, and GLP-1. Similar to Chen et al’s recent 2012 study, H. pylori
positive subjects had higher BMIs when compared to unaffected controls. After detection of H. pylori status, Francois et al administered a supervised 14 day course H. pylori eradication regime in all 44 H. pylori positive subjects, which included amoxicillin, clarithromycin and a proton pump inhibitor (PPI). After this H. pylori
eradication regime, subjects were found to have an increase in BMI, leptin and ghrelin which persisted for 18 months following the antibiotic therapy, despite steady BMI levels during the six months prior to in study (see figure below).
So can we assume from the above figure that eradication of the H. pylori will lead to increased BMI?. Could it be that H. pylori may offer some “metabolic protection” in those with preexisting insulin resistance or increased body mass index (BMI)?
What can we make of this new data?
This recent 2012 study by Chen et al raises more questions than answers. For this retrospective analysis found a positive, statistically significant association between increased age, BMI, glycated hemoglobin and H. pylori infection. Yet last year Francois et al found that individuals whom underwent H. pylori eradication were observed to have prolonged increases in BMI long after the antibiotic therapy commenced.
Are different detection methodologies to blame? Francois et al used two different H. pylori detection methodologies, ELISA IgG antibody and CagA antigens, while Chen et al relied solely on the CagA antigen methodology from NHANES data. Or could it be that the combination of the pharmacologic agents used in Francois et al’s eradication study created a dysbiotic small bowel, facilitating increased intestinal permeability and it’s associated metabolic endotoxemia-mediated disruption in energy homeostasis. What about post antibiotic repletion of gut microflora through targeted probiotic use?
Kim 2011 Basu, S., & Wiklund, L. (Eds.). (2011). Studies on Experimental Models: Helicobacter pylori-Induced Oxidative Stress and Inflammation(S. Basu & L. Wiklund, Eds.) (pp. 343–370). Totowa, NJ: Humana Press. doi:10.1007/978-1-60761-956-7_16