Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No.
3 • June/July 2012
Modification of Intestinal Microbiota for the Treatment of Disease:
Cardioprotection in Rats Experiencing a Heart Attack
With the discovery of the importance of the resident intestinal microbes (microbiota) in the maintenance of normal host physiology, researchers are now beginning to publish work on how the modification of the intestinal microbiota can be used to promote improved health or amelioration of disease states. A new paper is, therefore, of considerable interest. In this 2012 paper, researchers report that treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin in their drinking water resulted in decreased circulating leptin levels by 38%, 27% smaller myocardial infarcts (death of heart cells as a result of an experimental occlusion of the left anterior descending coronary artery), and improved recovery of postischemic mechanical function (35%) in treated as compared to untreated control rats.
The Dahl S rat “is an established model of increased susceptibility to injury from myocardial ischemia/reperfusion injury.” The minimally absorbed antibiotic vancomycin was used because it modifies the makeup of the resident intestinal bacteria, reducing infarct size “despite the absence of the antibiotic in the coronary perfusate at the time of ischemia/reperfusion, suggesting that a direct effect of the antibiotic on the heart is not responsible for the decrease in IS [infarct size].” In fact, the authors report that “when administered directly into the coronary circulation, [vancomycin] had no effect on severity of myocardial infarction.” The rats were treated with vancomycin for its effects on the resident intestinal microbes, decreasing the total numbers while altering the abundance of individual groups of the gut microbiota.
“The minimum treatment time vancomycin needed to decrease IS was 48 h.”(1) One of the effects of vancomycin was to decrease circulating leptin levels by 38 ± 4% and the researchers found that the administration of leptin to the vancomycin treated rats before ischemia/reperfusion abolished the decrease in IS.
Additional studies were performed by the researchers in which the rats were fed a commercial blend (Goodbelly) of two probiotics, Lactobacillus plantarum (Lp299v) and Bifidobacterium lactis (Bi-07) for 14 days before receiving ischemia/reperfusion treatment, resulting in a 29% decrease in infarct size in the probiotic supplemented rats as compared to the rats subject to the ischemia/reperfusion procedure but without probiotics pretreatment. Treatment with the two probiotics also decreased leptin levels in blood by 41% and, like vancomycin, pretreatment with leptin abolished the cardioprotection by the two probiotics.
The authors explain that leptin is synthesized and secreted into the circulation largely by white adipocytes (fat cells), but that the heart also produces and is responsive to leptin. They suggest that their data support a model of leptin resistance in the heart in which persistently high levels of leptin desensitizes the heart to leptin signaling. Conversely, reduced levels of leptin in the circulation increase the sensitivity of the heart to leptin. They suggest that the probiotics may have a cardioprotective effect by decreasing circulating leptin levels.
Interestingly, the researchers compared the protective effects of the vancomycin or probiotics to that of other widely used medical therapies. For example, they note that the vancomycin resulted in a 27% reduction in IS, while the two probiotics reduced IS by 29%. Early ischemic preconditioning, on the other hand, can cause an 86% reduction in IS, while late ischemic preconditioning can reduce IS by 66%. Remote preconditioning (where transient periods of nonlethal ischemia and reperfusion, such as can be produced by a short period of on and off by a blood pressure gauge cuff on a limb) can also provide substantial cardioprotection of 52% reduction in IS. Hence, the protection resulting from vancomycin or the two probiotics was much less than these other methods. However, the authors also note that the results with these agents are similar to the protection resulting from treatment with erythopoietin (39% reduction in IS) or thrombopoietin (34% reduction in IS). These are encouraging results and supplementation with the two identified probiotics is likely to be safer and cheaper than the use of therapeutic drugs and it must be remembered that the experimental investigation of probiotics for medical therapy has barely begun.
- Lam et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J 26:1727-35 (2012).