Dysfunction Of Enteric Neural Circuits In Colitis
In addition to immune cells, neurons in the ENS express 7nAChRs . The ENS consists of the intrinsic innervation of the bowel, a component of the autonomic nervous system with the unique ability to function independently from the CNS . Enteric ganglia are organized into two major ganglionated plexuses, namely the myenteric and submucosal plexus, and contain a variety of functionally distinct neurons, including primary afferent neurons, interneurons, and motor neurons, synaptically linked to each other in microcircuits. While the myenteric plexus mainly regulates intestinal motility, the submucosal plexus together with nerve fibers in the lamina propria are involved in regulating epithelial transport. These nerves form networks within the lamina propria of both crypts and villi with the terminal axons in close contact with the basal lamina, an ideal position not only to affect epithelial cell functions but also to detect absorbed nutrients and antigens. Substances released from epithelial cells may act on nerve terminals to change the properties of enteric neurons and cause peripheral sensitization. Consequently, permanent or even transient structural alterations in the ENS disrupt normal GI function. Since the ENS controls the motility and secretion of the bowel these abnormalities indicate the impact of inflammation on neural signaling in the ENS.
Figure 2Figure 3
Why Might Smoking Have A Protective Effect On Uc
The key is probably the nicotine in cigarette smoke. According to Crohns and Colitis UK, nicotine may suppress your immune system, decrease the inflammation of ulcerative colitis, and boost production of the mucus in the colon that acts as a protective barrier. Also, nitric oxide, a chemical released by nicotine, may help calm intestinal spasms that trigger the urge to have a bowel movement by reducing muscle activity in the colon.
All this is not to suggest that, if youre a smoker, you should forget about quitting in a bid to stave off ulcerative colitis. And if you dont smoke, it goes without saying that you should not consider taking it up. I advise all my patients to quit smoking because of its multitude of adverse effects on the body, says Matilda Hagan, MD, an inflammatory bowel disease specialist and co-medical director at the Center for Inflammatory Bowel and Colorectal Diseases at Mercy Medical Center in Baltimore. She notes that there are effective treatments, including drugs and other therapies, that address ulcerative colitis. Its true that those medications can have side effects, but the negative effect of smoking long-term outweighs any negative effects of UC medications.
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What Did It Find
- The study included 9,616 people with the first diagnosis of ulcerative colitis, 6,754 of whom had their smoking status recorded at the time of diagnosis. Around 40% had never smoked, 47% were former smokers, and 13% were current smokers. The proportion of smokers remained constant throughout the 12-year study period, in contrast to a decline in smoking rates in the general population.
- The cumulative rates of oral corticosteroid use at one, three and five years among smokers and ex-smokers were similar to the rates for non-smokers .
- The risk of a flare of symptoms requiring corticosteroid use was similar among smokers, compared with never smokers , and among former smokers compared with never smokers .
- Smoking status was not linked to hospitalisation .
- The rate of colectomy was similar in smokers compared with non-smokers .
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Risk Factors Associated With Ulcerative Colitis
This chronic condition has numerous risk factors. Just as many men as women develop ulcerative colitis over their lifetime. The following risk factors are associated with colitis:
Age Most cases of ulcerative colitis are diagnosed in adolescents and young adults however, it can occur at any age. Some surmise this may be due to the eating habits of the younger generation.
Race Inflammatory Bowel Disease often occurs in those with European and Jewish descent.
Family History Those who have a family history of inflammatory bowel disease are at an increased risk of developing this painful digestive disorder.
Medications Medications can increase the risk of developing ulcerative colitis. These medications include oral contraceptives, synthetic hormone replacement therapies and acne medications.
Place of Residence Where you live can contribute to a higher incidence of inflammatory bowel disease. Those who live in the United States and Europe have a higher risk of developing ulcerative colitis. Experts think this may be due to certain lifestyle factors, including pollution, diet and cigarette smoking.
Why Does Cigarette Smoking Affect Symptoms Of Ulcerative Colitis
Experts do not fully understand the apparent benefit of cigarette smoking on UC. Researchers are still trying to understand how cigarette smoking can be protective against UC for some people, especially because smoking has detrimental effects in Crohns disease, a related type of inflammatory bowel disease that also involves intestinal inflammation.
Researchers do understand that tobacco smoke has hundreds of components, including nicotine, carbon monoxide, and free radicals. It is thought that nicotine is the main component responsible for the protective effects of smoking on UC. It is believed that smoking the expression of gastrointestinal cytokines . Cigarette smoking may cause changes in intestinal motility the movements of the digestive system and the transit of its contents within and intestinal permeability, the control of material passing from inside the GI tract through the cells lining the gut wall. Cigarette smoking also can increase the thickness of the protective mucosal layer of the colon.
Studies have also shown that heavy smoking may suppress the immune system, an effect that goes away when you quit smoking. UC is an autoimmune condition, so smoking may lessen symptoms because it suppresses the immune system.
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Smoking’s Different Effects On Bowel Disease
UC is closely related to another digestive disease, . Together, they’re known as . But they have one striking difference: Smoking increases the risk of developing Crohn’s disease but decreases the risk of UC.
While many people with Crohn’s disease are smokers, most of those with UC are not. Many used to smoke, however. Quitting increases the risk of UC within two to five yearsand the effect lasts up to 20 years.
What’s more, when smokers with UC quit, they’re likely to have a flare-up of symptoms. Some studies suggest nonsmokers tend to have more severe cases of the disease. They may endure more hospitalizations, may require higher doses of medications, and are more likely to need surgery.
General Harmful Effects Of Cigarette Smoking
The main component of cigarette, tobacco, is a natural product with a complex molecular composition. During smoking, this complex biomass is subjected to high temperatures and varying oxygen concentrations, producing an incomplete combustion that generates more than 7,000 toxic compounds. Cigarette smoke can be divided into mainstream and sidestream smoke. Mainstream smoke is the fraction that the smoker inhales directly, and is composed of a particulate phase and a gas phase . Low molecular weight components, such as carbon monoxide and light aldehydes, are the main substances present in the gas phase, which immediately enters the pulmonary circulation . On the other hand, compounds such as nicotine, polycyclic aromatic compounds, nitrosamines, and heavy metals are predominantly found in the particulate phase, which is absorbed by mucous membranes, skin, alveoli, and the gastrointestinal system .
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Can Nicotine Replacement Therapy Help Colitis
With the money I saved, I treated myself to a new laptop. I felt that it was important to treat myself in recognition of giving up what had been a major habit in my life.
The NHS has a programme to help people stop smoking. For more information see nhs.uk/better-health/quit-smoking. Your doctor or any other healthcare professional should also be able to help you. Some pharmacists, private health insurers, employers and local governments offer programmes to help you stop smoking.If you have Colitis and are interested in giving up smoking, you are advised to discuss this with your IBD team. Some people with Colitis may find that their symptoms worsen when they stop smoking, so it could be helpful to have a plan in place in case this happens.The NHS can help with nicotine replacement therapy , which includes patches, gum, lozenges and inhalers. NRT gets nicotine into the bloodstream without smoking and its harmful side effects. Medicines such as bupropion or varenicline can be used to manage withdrawal symptoms.You may like to consider including counselling as part of your programme to stop smoking. Research has found that a combination of medication and counselling can be more effective than a single approach.
I was a smoker for 30 years, but when I was diagnosed with Crohns, my consultant advised me to give up. I tried, and managed to give up after a bowel resection operation.
What Are The Precautions When Taking This Medicine
The patch may contain conducting metal. Remove patch before MRI.
Gum chewing can cause problems with dental work.
When you stop smoking, other medicines may be affected. Talk with healthcare provider.
Check medicines with healthcare provider. This medicine may not mix well with other medicines.
If you have PKU, talk with healthcare provider. Some products do contain phenylalanine.
If pregnant and using patch, consider removal at night.
Tell healthcare provider if you are pregnant or plan on getting pregnant.
Tell healthcare provider if you are breast-feeding.
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Nicotine Alleviates Ulcerative Colitis
One of the earliest noted effects of nicotine on a peripheral tissue was in inflammation of the intestine. Early reports mentioned patients with ulcerative colitis who upon cessation of smoking experienced more severe disease progression, which was ameliorated by returning to smoking . In contrast, patients with Crohn’s disease experienced severe disease when smoking, requiring the immediate cessation of any tobacco product use . Crohn’s disease is a chronic inflammatory disease, which might affect any part of the GI tract, causing a wide range of complications including ulceration, fibrostenosis, and fistula development resulting in symptoms like abdominal pain, fever, diarrhea, and weight loss during episodes with flare-ups. Smoking also worsens the course of Crohn’s disease by increasing the risk of developing fistulas and strictures as well as accelerating the need for surgery, probably due to an increased influx of neutrophils into the intestinal mucosa . These detrimental effects of smoking in Crohn’s disease could also be related to the nicotine-induced suppression of antimicrobial activity and immune responses by macrophages , which might further compound any deficiency in the host response to luminal bacteria.
Nicotine And Crohn’s Disease
Smoking cigarettes actually has a detrimental effect on Crohn’s disease. People who smoke, or who have smoked in the past, have a higher risk of developing Crohn’s disease than non-smokers.
Crohn’s disease patients that smoke has an increased number of relapses and repeat surgeries and may require aggressive immunosuppressive treatment. People with Crohn’s disease are strongly encouraged by their physicians to stop smoking in order to prevent flare-ups of the disease.
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Ulcerative Colitis And Diverticulitis: Whats The Outlook
UC is a lifelong condition, and your symptoms may come and go. About 30% of people with UC have severe symptoms, and flare-ups might happen more frequently. While medications often help, surgery may also be needed.
In contrast, most cases of diverticulitis, even though itâs also considered a lifelong condition, clear up with a 7- to 10-day course of antibiotics and plenty of rest. If you have severe symptoms, talk to your doctor about other treatment options.
Managing your diet and stress and making time for regular physical exercise are key to lowering your risks for both conditions. However, because some of the symptoms are specific, there are steps you can take to avoid your condition flaring up or getting worse.
To prevent diverticulitis, you should:
- Eat more fiber. This helps your poop move better in your digestive tract and reduces any pressure on the colon walls
- Drink lots of water, this prevents constipation.
If youâre not sure what to eat, talk to your doctor.
To lower your odds for UC or manage flare-ups, you should:
- Get plenty of sleep. This can ease emotional stress and keep your immune system in check.
- Avoid using too many nonsteroidal anti-inflammatory drugs . For pain relief and fever, switch to alternatives like acetaminophen .
- Be careful when you take antibiotics. These drugs can trigger UC flare-ups. Let your doctor know if it does.
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Increased Severity Of Colitis In Mice Deficient In 7nachr
A major role of 7nAChR in colitis was demonstrated by the increased severity of colitis induced by dextran sulfate sodium in 7nAChR-deficient mice. 7nAChR-deficient mice lost significantly more body weight and had increased levels of proinflammatory cytokines in comparison to wild type mice as early as 3 days post-colitis . In addition, neither nicotine nor a selective 7nAChR agonist attenuated the degree of inflammation in 7nAChR-deficient mice. Nicotine has been found to reduce the LPS-stimulated production of TNF- and IL-1 from peripheral blood mononuclear cells from IBD patients . Thus, it is not surprising that excessive TNF- production as occurs in colitis can also be attenuated by activation of 7nAChR .
In isolated intestinal and peritoneal macrophages, nAChR activation enhanced endocytosis and phagocytosis and this effect induced a transiently enhanced mucosal passage of luminal bacteria, in agreement with the role of ACh in stress-induced epithelial permeability . The effect was mediated via stimulated recruitment of GTPase Dynamin-2 to the forming phagocytic cup and involved nAChR 4/2, rather than 7nAChR. However, despite enhanced luminal bacterial uptake, ACh reduced NF-B activation and pro-inflammatory cytokine production, while stimulating anti-inflammatory interleukin-10 production .
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Nicotine Might Be A Potential Treatment For Ucsomeday
Researchers are studying whether nicotine-replacement therapiesincluding gum, patches, and nicotine enemascan relieve UC symptoms in the same way smoking does. Although some people with UC report finding symptom relief from patches and gum, the science proving a benefit still isnt there. And right now, nicotine is not a recommended therapy for UC, Dr. Magier adds. He prescribes 5-aminosalicylic acid treatments , steroids, and anti-TNF injections instead.
Nicotine Suppresses The Production Of Pro
There is no doubt that the net effect of cigarette smoking is pro-inflammatory primarily as a result of increased oxidative stress, which occurs when the amount of reactive oxygen species generated in cells exceeds the capacity of normal detoxification systems . Oxidative stress is one potential explanation for the enhanced DNA breaks in smokers . Thus, it has implications for understanding the mechanisms by which smoking induces organ damage. There is overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema, and other serious diseases in smokers. Cigarette smoke contains molecules that act as potent carcinogens , as well as a large amount of ROS forming substances such as catechol or hydroquinone. However, nicotine, while being the addictive agent, is often viewed as the least harmful of these compounds. In fact, nicotine exhibits anti-inflammatory properties in many systems .
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Should Smoking Be A Treatment For Ulcerative Colitis
Smoking is not recommended as a treatment for UC. Tar, not nicotine, is the chemical in cigarettes most linked to cancer. That doesnt mean nicotine is good for you. Any product that includes this highly addictive substance may have a negative effect on your health.
There are 600 ingredients in addition to tar and nicotine in the average cigarette. When combined, these ingredients produce over 7,000 chemicals. Many are poisonous. Others are known to cause cancer.
Smokers with UC tend to experience more hospital stays and fewer positive health outcomes overall than those who dont smoke.
The increased risk of experiencing adverse health outcomes extends beyond just cigarettes. Smokeless tobacco contains at least 30 chemicals linked to cancer. Cancers associated with smokeless tobacco include:
- pancreatic cancer
Disease Outcome In Uc
The relation between smoking behavior and disease outcome variables in UC is depicted in . These data show a beneficial relation between active smoking and outcome in UC, except for pouchitis. Even with a longer follow-up, smoking UC patients had a lower colectomy rate, less PSC, and less backwash-ileitis than UC patients who never smoked. The development of pouchitis was not significantly different between smokers and never smokers, but patients who quit smoking before diagnosis had less pouchitis than smokers. Quitters before diagnosis had fewer hospitalizations and needed fewer oral steroids than quitters after diagnosis. Quitters before diagnosis more often had left-sided colitis and less often pancolitis during follow-up than never smokers.
Daily dose-effect of active smoking in ulcerative colitis. *P-value < 0.05 #P-value < 0.01 inflammation above proctum ¶azathioprine, 6-mercaptopurine, and/or methotrexate §hospitalizations once or more. 5-ASA: 5-aminosalicylates EIM: extraintestinal manifestations IQR: interquartile range IS: immunosuppressants PSC: primary sclerosing cholangitis.
We divided never-smoking UC patients into passive and nonpassive smokers. In contrast to the beneficial effect of active smoking, passive smokers developed more pouchitis and backwash-ileitis than nonpassive smokers . No effect of passive smoking was observed on the need for medication, surgery, and hospitalizations .
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How Is Treatment The Same And Different
In both conditions, treatments usually involve medications or, sometimes, surgery. In severe cases, your doctor may recommend a combination of the two to bring your symptoms under control. Certain over-the-counter medications may ease some of your pain-related symptoms. These include:
- Anti-diarrheal medications
- Iron supplements, especially if youâre bleeding
UC treatments may include:
Anti-inflammatory drugs. This is usually the first line of treatment. This can include drugs like 5-aminosalicylates and corticosteroids. Some newer drugs like sulfasalazine and 5-ASAs , which are called âsteroid-sparing,â can be safely taken long-term. Your doctor may not want you to take steroids long-term because of their side effects.
Immunosuppressant drugs. This helps to reduce inflammation in your colon and cut down the immune response that might attack your digestive cells.
Biologics. This targets the proteins made by your immune system.
Surgery. About 30% of people who have UC need surgery. Itâs sometimes the only cure, especially if medications donât ease your symptoms or they become too difficult to manage. Your doctor may consider a surgery called proctocolectomy.
In this procedure, your entire colon and rectum are removed. Most surgeries also involve a procedure in which your doctor will attach a pouch at the end of the small intestine or outside your body to pass poop directly into it.
Diverticulitis treatments may include: