Antimicrobial Blue Light for Eradication of Helicobacter pylori in Vitro and in Humans
摘要
Helicobacter pylori is a recalcitrant gram-negative bacterium, which can cause a variety of diseases in humans, including gastric and duodenal ulcers, as well as gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and can survive in the inhospitable gastric microenvironment, by adapting to this hostile milieu. H. pylori infection is usually treated with complex antibiotic regimens, but failure to eradicate the infection is common. When H. pylori was cultured in liquid media, significant quantities of coproporphyrin and protoporphyrin IX accumulated in the cells and were secreted into the medium. These photoactive porphyrins led to cell death (up to 5 logs) by photodynamic action after illumination with low doses of blue/violet light. Both virulent and drug-resistant strains were killed. A controlled, prospective, blinded, clinical trial of endoscopically delivered visible (blue) light to eradicate H. pylori in regions of the gastric antrum was carried out in ten chronically infected symptomatic patients. Blue light (405 nm, 40 J/cm2) was delivered to a 1-cm diameter spot in the gastric antrum via an optical fiber passed through the endoscope, and weighed biopsies were taken from treated and control spots and quantitatively cultured to enumerate H. pylori colonies. The mean reduction in H. pylori colonies per gram of tissue between treated and control spots was 91% (P < 0.0001). Some patients had reductions approaching 99%. A second controlled, prospective clinical trial was conducted using a novel light source consisting of laser diodes and diffusing fibers encased in an inflatable balloon to deliver 405-nm illumination at escalating total fluences to the whole stomach. Eighteen adults (ten female) with H. pylori infection were treated at three US academic endoscopy centers. Quantitative bacterial counts were obtained from biopsies taken from the antrum, body and fundus, and serial urea breath tests. The largest reduction in bacterial load was in the antrum (>97%), followed by body (>95%) and fundus (>86%). There was a correlation between log reduction and initial bacterial load in the antrum. The urea breath test results indicated that the bacteria repopulated in days following illumination. To improve the patient friendliness of this approach, a different group of researchers designed a blue light-emitting capsule that could be swallowed, but this device has not yet been tested in patients.