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So some people might already know this, but I have ulcerative colitis. After the whole cancer thing, it's gotten actually quite a bit better. But treating it has been pretty difficult over the course of my life. Hasn't been fun the whole time, I'll tell you what. There was a couple of years there I could not fart safely. Ulcerative colitis is one of a few kinds of inflammatory bowel diseases, and those diseases can be very bad for anyone that has them. There's no cure, and the treatments aren't always effective for everybody. But new research suggests that a promising treatment for certain types of chronic inflammatory bowel disease might come from something that
we know is absolutely terrible for you in every other way: smoking. [♪ INTRO] Let's start with a quick note on what we're talking about here. Crohn's disease and ulcerative colitis are both forms of inflammatory bowel disease, AKA IBD. The classic characteristic of both these diseases is that, like the name suggests, they cause inflammation and damage in your gut. This is different from IBS or irritable bowel syndrome, which definitely causes pain and discomfort, but doesn't cause physical damage to your GI.
No inflammation, hence, not IBD. It's annoying that IBD starts with I, but it's a different I. Inflammation or irritable. So for this video, I'm talking about IBD. I'm not talking about IBS. There are also a few conditions that don't exactly look like Crohn's or ulcerative colitis, so those can land in the super helpful "IBD unclassified" category. But most of the time IBD is referring to ulcerative colitis or Crohn's disease. Symptoms of both Crohn's and UC can include nausea, gut pain, weight loss, fatigue, and some, shall we say, unpleasant bathroom experiences.
Those symptoms can cool off or flare up depending on medications you're taking, what food you've eaten recently, your level of stress or just complete and total randomness. And IBD of any type can cause problems outside of your gut too. All that inflammation in your gut can make it harder for your body to absorb enough nutrients. Some research estimates that up to 85% of people with IBD suffer from malnutrition. In adults, that can cause weight loss, but for children, it can even stunt their growth. And as your body struggles to absorb things like protein, vitamins, or electrolytes, it can affect your whole body, including your muscles, bones, skin, hair, and eyes.
In particular, these conditions make it harder to absorb iron, and that combined with the literal wounds in your gut can lead to anemia. While your guts might be draining like a faucet, your blood and energy reserves are too, causing fatigue. So not only are you feeling crappy, you're just generally pooped too. So, why does this happen? Well, it's all thanks to your immune system going rogue and not doing what it's supposed to do. They're all autoimmune disorders, where your immune system gets its wires crossed and starts attacking your gut tissue. Researchers are still trying to identify an exact cause, and right now it seems like there are multiple things
that can contribute to someone's risk of developing IBD. Genetics is a big one, and researchers are investigating whether mutations related to reigning in your immune system, managing your gut bacteria, and determining the thickness of your gut's mucus barrier might play a role. Then the environmental factors, like antibiotics, processed foods, or stress, might step in to piss off your immune system and trigger the disease if you have the genetics to predispose you to that kind of thing. But even with all this overlap between Crohn's disease and ulcerative colitis, they are distinct diseases, and the main difference is where the problem shows up in the gut.
Ulcerative colitis strikes the rectum and colon, while Crohn's can target anywhere in the GI tract, though it seems to prefer the end of the small intestine and the beginning of the large intestine. There's also a difference when it comes to exactly how the immune system freaks out. In Crohn's disease, immune cells called T helper cells type 1, or TH1s, seem to be the main culprit. And in ulcerative colitis, it's the atypical T helper cells type 2, or TH2s, that cause the most trouble. Both types of cells produce cytokines, which are signaling molecules. Think of them as your immune systems version of a flare gun.
All of those cytokines trigger the inflammatory response and activate other immune cells, calling the immune system to battle against the gut tissue itself. So all of this is pretty bad, which is why there's been so much work investigating how to treat these diseases. And at least when it comes to UC, it seems like a potential treatment might also be the one thing that we all know is terrible for our health: smoking. You've heard this everywhere: smoking is bad for you. Your lungs hate smoking. Your heart and blood vessels hate smoking.
Your brain hates smoking. Heck, even your eyes, reproductive system, and pancreas hate smoking. Smoking is associated with everything from strokes to diabetes, heart attacks, and an absolute smorgasbord of cancers. But researchers have noticed a weird connection between smoking and UC, but this time, it's a good thing. As in, their ulcerative colitis gets better if they smoke. People first started noticing correlation back in the '80s. Some researchers realized that only a very small fraction of the ulcerative colitis patients at their clinic were smokers. And whether you were alive back then or have ever seen
an episode of Stranger Things, that might make you raise an eyebrow, because smoking was super popular in the '80s. Having a small number of smokers in any group of people was pretty unusual. In their study, 44% of people smoked in the control group, but only 8% of ulcerative colitis patients were smokers. According to survey data, smoking rates through the '80s in the UK ranged from about 30 to 35%, so these ulcerative colitis patients were weird even among the general public. They also found that non-smokers were anywhere from three to six times more likely to develop ulcerative colitis than smokers were. With numbers like that, you don't need a gut feeling to know something weird was going on.
So, researchers knew that smoking had a protective effect against ulcerative colitis. What was less clear was why. In the 1990s, scientists had done a handful of clinical trials where they tried to treat ulcerative colitis with nicotine gum, patches, or even enemas. At the time, they hypothesized that nicotine might make mucus in the colon thicker, helping to protect the tissue, or that it might help suppress immune response. But those explanations don't exactly fit, because those kinds of changes would be expected to improve any autoimmune disease affecting the gut. And as it turns out, not all forms of IBD like it when you light up.
In fact, while smoking decreases your risk of getting ulcerative colitis, it increases your overall risk of getting Crohn's disease. And while treating Crohn's disease isn't always easy, quitting smoking is one of the few things you can do to improve your symptoms. Remember those environmental factors that can increase risk of developing IBD? Smoking is one of them, at least when it comes to Crohn's. Plus, people who continued smoking after they got diagnosed with Crohn's disease were more likely to have a poorer outcome and more frequent flare-ups.
Smoking might also increase the need for hospital stays and surgical intervention. All in all, smoking seems to be very bad for people with Crohn's disease. Which also means that a lot of those ideas from the '90s about nicotine doing stuff to your gut don't make sense, because if it was that simple, then Crohn's patients would see just as many benefits as ulcerative colitis patients do. So researchers knew something else had to be going on in order for smoking to be so good for one IBD and so bad for the other. And good news! They think they've cracked it. It's all about your gut bacteria.
Now, there's evidence that nicotine specifically can help to suppress those TH2 cells that are so overactive in ulcerative colitis, but that's not the whole story. A study from the RIKEN Center for Integrative Medical Sciences found that a better answer might already be on the tip of your tongue. Everybody's got a whole community of bacteria living in our mouths. Yes, even if you're really good about brushing your teeth.
Most of them don't cause any trouble, and a few are even good for you. One of those common mouth bacteria are Streptococcus species. Don't worry, these aren't the kind that give you strep throat or cause flesh eating diseases or anything like that. They're the good guys! And when you swallow, bacteria in your mouth can travel down your GI with your saliva, including those Strep bacteria. Usually, they just get a free ride all the way through it to your toilet. The weird thing was that in people with ulcerative colitis who smoke, researchers found a buttload of these Streptococcus bacteria in their colons.
Something about smoking was letting this oral bacteria stick around in the colon, rather than just pass through. The researchers swabbed smokers' mouths for that oral bacteria, isolated several species, and then put them into the guts of mice with either Crohn's or ulcerative colitis. They found that it was specifically Streptococcus mitis that mimicked the effects of smoking. Giving it to the ulcerative colitis mice caused their inflammation to go down. But in the Crohn's disease mice, it led to inflammation up the wazoo.
Even though this bacteria is usually harmless in healthy people, it has a direct effect on IBD symptoms. And since IBDs are the immune system going out of whack, the next step was for the researchers to see how this bacteria can influence the immune system at large. They found that Strep mitis triggers an increase in TH1 cells in the gut, which means for Crohn's disease, it takes a crappy situation and makes it crappier. But in ulcerative colitis, since the major cell responsible is TH2, bonus TH1 is no problem. It turns out the increase in TH1 cells can actually help combat the TH2 cells, which is what reduces the colitis inflammation.
All of that explains how Strep mitis can exacerbate or improve IBD depending on the condition, but it still doesn't explain why smoking makes those bacteria stick around in the gut. So to answer that, the researchers had to circle back to what smoking leaves behind. When you smoke a cigarette, the burning of the tobacco produces benzene, which is a carcinogenic chemical. That gets into your lungs through the smoke that you are inhaling, and then your body then breaks that down into a bunch of other stuff, including a metabolite called hydroquinone. That metabolite was, unsurprisingly, found at much higher concentrations in the guts of smokers than non-smokers.
Previous research has found that hydroquinone can have immunosuppressive effects, which could help dampen ulcerative colitis all on its own. And it's that immunosuppression that makes the gut less equipped to stop your mouth bacteria from setting up shop in your colon. In fact, hydroquinone seems to promote the growth of Strep mitis in the intestines. So smoking leads to more hydroquinone, which allows for Strep mitis from the mouth to grow in the intestines, which then increases the presence of TH1 cells, reducing TH2 cells and the ulcerative colitis inflammation that comes with them. Simple!
Now to be clear, this was a relatively small study, but it does explain why smoking both eases ulcerative colitis symptoms and makes the symptoms of Crohn's disease worse. And I know what you're thinking. Anyone with ulcerative colitis, should they just like pick up smoking? Well, no. Smoking is still very bad for the rest of your body, and ulcerative colitis won't stop you from getting lung cancer from those cigarettes. Instead, the researchers propose that future treatment options might be planting this bacteria into the colons of people with ulcerative colitis, or even just giving them hydroquinone directly.
And they've actually tried that second option, at least in animal models. A study from 2014 gave mice with ulcerative colitis an oral form of hydroquinone called zonarol to see how it affected their symptoms. And the findings were pretty significant. Mice in this treatment group had fewer pro-inflammatory molecules, smaller ulcers, fewer disease symptoms like bloody stools, and fewer immune cells attacking in general. But that's just how it worked in mice. Right now, the only hydroquinone on the market for humans is designed to treat hyperpigmentation, and it's only FDA approved to go on the skin.
There is no safe oral option for people, and there's also some evidence that hydroquinone could be harmful to the liver, so unless a doctor tells you otherwise, hydroquinone in any form shouldn't be considered a viable treatment for UC. Figuring out how to get hydroquinone safely to the gut without damaging the liver would be part of the battle, and that's if we can even confirm that it works as well in us as it does in mice. It often doesn't and also it often does more damage to our bodies than it does to the bodies of mice. There's reasons we do this research. For the average person, trying to get Strep mitis into your colon also isn't an option.
Permanently changing the gut microbiome isn't as easy as swallowing a pill or even doing a fecal transplant, since you'd need the bacteria to survive this sudden relocation in order to reap the benefits. Plus, there could always be unforeseen consequences when you mess with the gut microbiome, since it can affect everything from weight and allergies to your brain and risk of cancer. But this research at least explains why smoking benefits colons with ulcerative colitis, and why it very much doesn't benefit intestines afflicted with Crohn's. And for diseases with no known cure, that's at least a step in the right direction. But remember, no matter what your colon thinks, smoking is still bad!
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