The gut is often considered the body's "second brain," with roles in mood regulation and immune function that expand beyond its primary job of digestion. The gut-brain axis is a bi-directional system comprising immune, endocrine, and neuronal components [1,2]. An intricate balance of the gut microbiota, mucosal integrity, and immune function is vital for optimal health.
It’s perhaps unsurprising that nicotine, the primary active compound found in tobacco products, has been the topic of intense research due to its wide-ranging effects on the body. The effects of tobacco, and thus nicotine, on the cardiovascular and respiratory systems are well known [3] and have been for many decades. More recently, research has started to unravel the impact of nicotine on gut health. We have previously covered GABA's role in gut health here.
This article looks at the complex relationship between nicotine and the gastrointestinal (GI) tract, examining its potential benefits and detrimental consequences as well.
What is Nicotine and How Does It Work?
Nicotine is an alkaloid found predominantly in the tobacco plant. Acting primarily on the nervous system, it binds to nicotinic acetylcholine receptors (nAChRs) to exert its effects. These receptors are not confined to the brain and central nervous system; they are also represented in various peripheral tissues, including the gut [4]. You can read more on nicotine's cognitive benefits here.
When nicotine binds to nAChRs, it triggers a series of events that alter signaling within cells. In the central nervous system, this can bring about enhanced concentration and mood [5]. In the gut, however, nicotine can influence neurotransmission, gut motility, and even alter the secretion of hormones involved in digestion [6,7]. These changes can have downstream effects on the gut microbiome and the immune environment of the GI tract.
Why is the Gut Microbiome Important?
The human gut houses trillions of microorganisms that include bacteria, viruses, and fungi, known collectively as the gut microbiome. These microorganisms play important roles in digesting food, recovering nutrients, synthesizing vitamins, and protecting against pathogens [8-10]. An imbalance, or dysbiosis, of the microbiome is associated with a range of health issues, including obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and autoimmune diseases [4,11].
Diet, antibiotics, stress, and lifestyle habits such as smoking significantly affect the composition of the gut microbiota. As research deepens our understanding of these factors, the specific impact of nicotine on this delicate balance is coming into focus. While nicotine itself is not a nutrient, its pharmacological actions indirectly influence the gut environment, thereby affecting microbial diversity and function.
Nicotine and the Gut Microbiome
Several studies have shown that exposure to nicotine can lead to shifts in the gut microbiome and its composition. In rodent models, nicotine has been associated with changes in bacterial populations [12], often bringing about a decrease in microbial diversity. Reduced diversity signifies a less resilient microbiome that could be more susceptible to inflammation and its associated conditions [13,14].
Although the mechanisms by which nicotine alters the gut microbiome are still under study, one theory is that nicotine increases the intestinal pH, which possibly benefits certain bacteria, enabling them to thrive and leading to gut dysbiosis [15].
The Paradox of Nicotine in Inflammatory Bowel Diseases
An intriguing feature of nicotine and its effects on gut health is its paradoxical role in inflammatory bowel disease (IBD). Crohn’s disease and ulcerative colitis are both IBDs and are characterized by chronic inflammation of the GI tract. Epidemiological studies have noted that smoking (and therefore high-dose nicotine) seems to have divergent effects on both conditions [16].
Crohn’s disease tends to worsen, or be exacerbated by nicotine exposure, whereas the risk of ulcerative colitis is increased in people who formerly or have never smoked. It’s thought that smoking has different effects on the small and large intestine, and that the effects of smoking/nicotine on each condition depend on the site of inflammation and not the type of disease per se [17].
The varied effects of nicotine on different types of IBD highlight the importance of personalized medicine. While nicotine patches might be beneficial for some patients with ulcerative colitis [18,19], they could exacerbate symptoms in those with Crohn’s disease [20]. Healthcare providers must weigh these factors carefully when considering treatment options and emphasize that the potential benefits of nicotine should be carefully balanced against its risks.
Nicotine and Intestinal Barrier Integrity
The intestinal barrier is a fundamental aspect of gut health, preventing harmful substances and pathogens from entering the bloodstream while allowing essential nutrients to pass. The barrier is composed of tightly connected epithelial cells, mucosa, and immune cells that work to maintain gut integrity.
Research indicates that nicotine may disrupt the intestinal barrier in several ways [12,21]. By altering the secretion of mucus and affecting the tight junction proteins between epithelial cells, nicotine can increase intestinal permeability. This is often referred to as “leaky gut syndrome.” Increased permeability allows bacteria and toxins to enter the bloodstream, potentially triggering systemic inflammation and contributing to the development of autoimmune diseases.
Conclusion
The relationship between nicotine and gut health is a complex interplay of beneficial and detrimental effects. While nicotine’s interaction with nicotinic receptors can lead to anti-inflammatory effects that might benefit certain conditions, such as ulcerative colitis, its overall impact on the gut microbiota and intestinal barrier function raises significant concerns. Nicotine-induced dysbiosis, increased intestinal permeability, and systemic inflammation underscore the risks associated with long-term exposure, either through smoking or e-cigarette use.
It’s important to note that you should not smoke or vape your nicotine. But in small doses (under 4 mg/day), nicotine can actually enhance memory, focus, and cognitive performance. It’s even being studied for its effects on inflammation, Alzheimer’s, and neurotransmitter support, highlighting its potential beyond recreational use. You can read more on this in our blogs here and here.
Ongoing research continues to uncover the precise mechanisms by which nicotine alters gut health, offering hope for targeted therapies that can leverage its benefits while mitigating its harms. For now, the evidence suggests that while nicotine might offer temporary relief for specific conditions, the broader implications for gut health and, by extension, whole-body health necessitate a substantial amount of caution.
References
[1] J. Ochoa-Repáraz, L.H. Kasper, The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?, Curr Obes Rep 5 (2016) 51–64. https://doi.org/10.1007/s13679-016-0191-1.
[2] L. Ye, R.A. Liddle, Gastrointestinal hormones and the gut connectome, Current Opinion in Endocrinology, Diabetes & Obesity 24 (2017) 9–14. https://doi.org/10.1097/MED.0000000000000299.
[3] M. Herman, R. Tarran, E‐cigarettes, nicotine, the lung and the brain: multi‐level cascading pathophysiology, The Journal of Physiology 598 (2020) 5063–5071. https://doi.org/10.1113/JP278388.
[4] L. Rueda Ruzafa, J.L. Cedillo, A.J. Hone, Nicotinic Acetylcholine Receptor Involvement in Inflammatory Bowel Disease and Interactions with Gut Microbiota, Int J Environ Res Public Health 18 (2021) 1189. https://doi.org/10.3390/ijerph18031189.
[5] A.J. Waters, S.R. Sutton, Direct and indirect effects of nicotine/smoking on cognition in humans, Addictive Behaviors 25 (2000) 29–43. https://doi.org/10.1016/S0306-4603(99)00023-4.
[6] S.S. Ali, E.A. Hamed, N.N. Ayuob, A. Shaker Ali, M.I. Suliman, Effects of different routes of nicotine administration on gastric morphology and hormonal secretion in rats, Experimental Physiology 100 (2015) 881–895. https://doi.org/10.1113/EP085015.
[7] E.R. Gritz, A. Ippoliti, M.E. Jarvik, J.E. Rose, S. Shiffman, A. Harrison, H.V. Vunakis, The effect of nicotine on the delay of gastric emptying, Aliment Pharmacol Ther 2 (1988) 173–178. https://doi.org/10.1111/j.1365-2036.1988.tb00685.x.
[8] J.G. LeBlanc, C. Milani, G.S. De Giori, F. Sesma, D. Van Sinderen, M. Ventura, Bacteria as vitamin suppliers to their host: a gut microbiota perspective, Current Opinion in Biotechnology 24 (2013) 160–168. https://doi.org/10.1016/j.copbio.2012.08.005.
[9] W.M. De Vos, H. Tilg, M. Van Hul, P.D. Cani, Gut microbiome and health: mechanistic insights, Gut 71 (2022) 1020–1032. https://doi.org/10.1136/gutjnl-2021-326789.
[10] E.A. Eloe-Fadrosh, D.A. Rasko, The Human Microbiome: From Symbiosis to Pathogenesis, Annu. Rev. Med. 64 (2013) 145–163. https://doi.org/10.1146/annurev-med-010312-133513.
[11] P. Bandopadhyay, D. Ganguly, Gut dysbiosis and metabolic diseases, in: Progress in Molecular Biology and Translational Science, Elsevier, 2022: pp. 153–174. https://doi.org/10.1016/bs.pmbts.2022.06.031.
[12] L. Chi, R. Mahbub, B. Gao, X. Bian, P. Tu, H. Ru, K. Lu, Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner, Chem Res Toxicol 30 (2017) 2110–2119. https://doi.org/10.1021/acs.chemrestox.7b00162.
[13] M. Kriss, K.Z. Hazleton, N.M. Nusbacher, C.G. Martin, C.A. Lozupone, Low diversity gut microbiota dysbiosis: drivers, functional implications and recovery, Current Opinion in Microbiology 44 (2018) 34–40. https://doi.org/10.1016/j.mib.2018.07.003.
[14] O.C. Thompson-Chagoyán, J. Maldonado, A. Gil, Aetiology of inflammatory bowel disease (IBD): Role of intestinal microbiota and gut-associated lymphoid tissue immune response, Clinical Nutrition 24 (2005) 339–352. https://doi.org/10.1016/j.clnu.2005.02.009.
[15] X. Gui, Z. Yang, M.D. Li, Effect of Cigarette Smoke on Gut Microbiota: State of Knowledge, Front. Physiol. 12 (2021) 673341. https://doi.org/10.3389/fphys.2021.673341.
[16] S. Bridger, J.C.W. Lee, I. Bjarnason, J.E.L. Jones, A.J. Macpherson, In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn’s disease and non-smokers develop ulcerative colitis, Gut 51 (2002) 21–25. https://doi.org/10.1136/gut.51.1.21.
[17] A. Karban, Effect of smoking on inflammatory bowel disease: Is it disease or organ specific, WJG 13 (2007) 2150. https://doi.org/10.3748/wjg.v13.i15.2150.
[18] Guslandi, Nicotine treatment for ulcerative colitis, Brit J Clinical Pharma 48 (1999) 481–484. https://doi.org/10.1046/j.1365-2125.1999.00039.x.
[19] V. Kannichamy, I. Antony, V. Mishra, A. Banerjee, A.B. Gandhi, I. Kaleem, J. Alexander, M. Hisbulla, S. Khan, Transdermal Nicotine as a Treatment Option for Ulcerative Colitis: A Review, Cureus (2020). https://doi.org/10.7759/cureus.11096.
[20] J. Cosnes, Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice, Best Practice & Research Clinical Gastroenterology 18 (2004) 481–496. https://doi.org/10.1016/j.bpg.2003.12.003.
[21] A. Sharma, J. Lee, A.G. Fonseca, A. Moshensky, T. Kothari, I.M. Sayed, S.-R. Ibeawuchi, R.F. Pranadinata, J. Ear, D. Sahoo, L.E. Crotty-Alexander, P. Ghosh, S. Das, E-cigarettes compromise the gut barrier and trigger inflammation, iScience 24 (2021) 102035. https://doi.org/10.1016/j.isci.2021.102035.
Comments (0)
There are no comments for this article. Be the first one to leave a message!