Host Barriers – Gastrointestinal and Genitourinary Tracts

00:00 Let's move on to the GI tract. So, the GI tract has got a lot of barriers in place. I mean basically everything we put in our mouth, the mouth is a dirty place too, but everything we put into our mouth has got some sort of microbial contamination. So we really have to have a very robust set of barriers to prevent invasion through the GI tract. So it starts near the top, there is acid secretions from the stomach mucosa. That low pH will kill off many many many microorganisms, it's like dumping acid on them. There is epithelial mucus, so lining every part of the GI tract from top to bottom. There is a thin layer of epithelial mucus that will trap up microbes and unless they can really move quickly, they are slowed down and kind of this mucus mock and cannot get into the cells below it. If you're down now into the small bell, there are pancreatic enzymes and bile salts that will either eat or just proteolytically cleave bacteria and other microbes, or will cause the balls to dissolve because of the bile salt. As in the lungs, there are a number of antibodies secretory immunoglobulin A and defensins and cathelicidins. Other elements that will be secreted into the lumen will be very protective in that way. There is a very large microbiome as we're all well aware of commensal organisms and so they make the environment relatively non-hospitable to the new microbes setting up shops. So it's reasonably hard for a new microbe to come in when there is already every niche in the GI tract that's been filled by microbes that are better suited to that environment to begin with. And then, the GI tract is constantly clearing itself. So once or twice a day depending on who you are, you are vacating everything that's in that lumen out the other end. Okay, so if I may be successful in getting past that barrier, what do I have to do? Well, okay, you have to be adhesive, you do have to make enzymes that can breakdown some of the mucus so we may have to make toxins to make the epithelium lyse or go away so that you can access what's underneath it and get through that mucus barrier. You may have to take advantage or may require that there be some other epithelial injury due to some other sort of trauma or if there is diminished function. So, if we lose peristalsis, if we lose the ability to make mucus, if we have diminished defensin or secretory immunoglobulin A production. All of those things will allow a microbe that might not otherwise be successful to get in. And then, you can also take advantage of antibiotics. So, antibiotics are not just targeted against one organism. In fact, they will tend to deplete many of the bugs that are in the microbiome. Suddenly I've taken the population that's in there of all those commensal organisms that have filled every niche and I wiped them out with the dose of an antibiotic.

03:21 Now a new bug can come in instead of stop because there is not as much competition.

03:27 So, that maybe a mechanism by which invaders are successful in the GI tract. Let's talk about the GU tract, genitourinary tract. So, first off, again 2, 3, 4, 5 times a day. If you drink a lot of water that you're supposed to, then there's constant urinary flushing. So there's not much of an opportunity, there's not much dwell time if a microbe is in your bladder or urethra. It's constantly being flushed out. And then the vaginal vault in particular.

03:55 There is a very low pH due to glycogen breakdown by the lactobacillus, which is a normal commensal organism in that location. So, the constant flushing in the vaginal vault, this low pH combined to be a fairly effective barrier. So, if I'm going to be successful, what do I have to do? Again, I have to be adhesive. Alright. I have to be able to stick. Even though the bladder is emptying, I'm going to be sticking to that epithelium and not be flushed out with all the urine. You may have to take advantage of other epithelial injury or diminished urinary flow. So patients who have neuro injury and have bladder stasis because they're not regularly voiding, now we're not having that regular flushing of the contents and bugs can take advantage of that. And finally, particularly in women who take antibiotics that will kill off the lactobacillus, they no longer have that low pH in the environment and then frequently there will be a secondary infection of candida. And so a yeast infection following antibiotics is not an uncommon phenomena and that's where the bug is now taking advantage of the antibiotics to eliminate that nice commensal organism that lives with the lactobacillus.