The gastrointestinal (GI) tract plays a vital role in the ability to digest and absorb nutrients from food. The GI tract is inhabited by a diverse community of microorganisms that provide nutrients and protection while breaking down hard to digest foods. The balance of microflora in the gut is crucial for one’s health and well- being, as an imbalance can lead to illness and disease.
Inflammatory bowel disease (IBD), a chronic condition characterized by inflammation of the GI tract, is one such disease. IBD consists of two conditions, Crohn’s disease, and ulcerative colitis, with the main difference being where the inflammation is occurring in the GI tract.
Prolonged inflammation in IBD can result in irreversible damage and an increased risk of developing colorectal cancer (CRC). There is a relationship between a healthy gut microbiota, the factors that influence its balance such as diet, lifestyle, medication, and stress, and the risk of IBD and CRC.
Here, we explore current research in the diagnosis, current and future treatment, and preventive measures for both IBD and CRC. As research on the gut microbiome continues to advance, it is crucial to recognize the individuality of gut health, and to tailor treatments accordingly.
There is also a need for ongoing research to further understand the pathogenesis of IBD and CRC as well as the potential for personalized medicine and targeted therapies with the hopes of improving the outcomes of individuals affected by these gut-related diseases.
Understanding Gut Health
The human gastrointestinal tract is made up of several organs that are involved in digesting and absorbing nutrients from the food you eat. The upper GI tract includes the mouth, esophagus, stomach, and part of the small intestine (duodenum) (1). The lower GI tract consists of the rest of the small intestine along with the large intestine (colon) and the anus (1).
The main function of the GI tract is to break down food into a digestible form in which it can be separated into absorbable nutrients and waste (2). To effectively breakdown food and absorb nutrients, the human body depends on what is known as the gut microbiota. Within the human gut live millions of microorganisms such as bifidobacterial, lactobacilli and even Escherichia coli.
A proper balance in these microorganism communities is essential to maintaining a healthy gut. There are bacteria within the normal gut microbiota known as opportunistic pathogens, meaning that while they are harmless if in balance, they can create illness and disease if they were to become unbalanced, such as an overgrowth of E. coli.
There are many factors that influence the health of the gut microbiome such as diet, lifestyle, medications, and stress. Diet is believed to play a large role in the maintenance of a healthy gut. Eating food that is healthy and contains the proper nutrients for your body plays a large role in the homeostasis, or proper balance, of the gut microbiota (3).
Lifestyle also can impact the health of the gut. Being active and exercising has been linked to maintaining and improving a normal gut flora (4). Certain medications have been linked to dysbiosis (imbalance) of the gut as well, such as some antibiotics since many antibiotics do not discriminate between healthy and harmful bacteria. A reduction in good bacteria often leaves the gut open to potential infection (5).
Stress has also been linked to a disruption in the gut microbiome. Overall, the GI tract plays a crucial role in the ability to properly receive nourishment. Disruption of any part of the GI tract, especially to the normal gut microbiota, can lead to unfavorable effects on the body.
Gut Dysbiosis and Inflammation
Within the human GI tracts are trillions of microorganisms such as bacteria, viruses, and even eukaryotes. Bacteria make up most of the microbes in the gut and maintaining homeostasis of these bacteria is a key aspect of having a healthy gut microbiota.
Humans have a symbiotic relation with the many microorganisms that inhabit the GI tract, and the microbes have a communal relationship with each other (6). The food we eat provides nourishment to the microbes, and they in turn provide us with essential amino acids, vitamins, and protection from harmful bacteria.
The gut microbiome differs from person to person and can change over the course of one’s life. However, the gut microbiome can be altered in a way that can be negative to the host due to environmental factors such as antibiotics, alcohol, and a poor diet. These factors can lead to dysbiosis of the microorganisms in the GI tract, leading to infection from harmful bacteria, or even the development of diseases.
In a typical gut, the GI tract has a variety of defense mechanisms including the thick mucus that covers most of the GI tract, the secretion of antimicrobial peptides, and the lack of space between epithelial cells to prevent the invasion of infectious material (7).
Dysbiosis of the gut can lead to changes in the mucus layers, epithelial cell damage, and inflammation of the GI tract which increases the risk of illness or disease (5). Once dysbiosis occurs in the gut microbiome, it can be difficult to return it back to a homeostasis state. Prolonged dysbiosis has been linked to the occurrence of certain health disorders such as inflammatory bowel disease.
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) encompasses two conditions Crohn’s disease and ulcerative colitis. These conditions lead to chronic inflammation of the GI tract, which can ultimately result in damage. While both IBDs are identified by the inflammation they cause, they are different due to the affected area and the type of damage that is caused.
Crohn’s disease typically affects the area of the small intestine that is just before the large intestine, while ulcerative colitis affects the large intestine and the rectum. Crohn’s has patches of damaged areas, while UC has continuous areas. Lastly, the inflammation in Crohn’s can be found in multiple layers of the GI tract wall, while UC is only found in the innermost layer of the colon lining (8).
Currently, the prevalence of IBD is greater than 0.3% in Western countries and is increasing in newly industrialized countries (9). There are approximately 4.90 million cases worldwide as of 2019, and while the incidence appears to be stabilizing in Western countries, it is increasing due to urbanization in regions such as Asia, Africa, and South America (10).
The increase in prevalence can partially be attributed to risk factors such as smoking, urban living, appendectomy, tonsillectomy, antibiotics, oral contraceptives, soft drinks, vitamin D deficiency, and non-HPL-EHS (11). The most common symptoms affecting patients with IBD include diarrhea, abdominal pain, GI bleeding, and weight loss (12).
To diagnosis the disease, a GI doctor will typically run some blood tests and a stool test to look for markers such as C-reactive protein and fecal calprotectin (pro-inflammatory proteins). They might also conduct an endoscopy and colonoscopy to identify the area of the GI that has been damaged and what kind of damage is occurring.
Once IBD has been identified, treatment can begin. While there is no known cure for IBDs. Treatment usually involves the use of anti-inflammatory drugs and immunomodulators to decrease inflammation and regulate the immune system (7).
Other treatments include monoclonal antibodies, thalidomide, and drug-loaded microcapsules. Many studies have investigated the impacts of chronic inflammation on the gut and its long-term consequences.
Prolonged inflammation can lead to irreparable damage to the GI tract that can lead to the removal of the colon leading to a colostomy bag. It has also been documented that chronic inflammation is linked to cancer, and there is an increased risk of developing colorectal cancer (CRC) in patients with IBD (13).
Link Between IBD and Colorectal Cancer (CRC)
There are many risk factors that can increase a person’s likelihood of developing colorectal cancer. One such risk factor is chronic and reoccurring inflammation. This risk factor has been linked to an increased chance of developing cancer near the site of persistent inflammation (14).
A known example of this is the increased risk of CRC in patients with IBDs. Current research indicates that the increased risk is due to the pro-neoplastic effects of chronic inflammation of the intestinal tract (13).
Typically, the development of CRC in IBD patients begins with dysplasia in the intestinal cells. These sites later can manifest into invasive adenocarcinoma (13). Research has found that samples of tissue from the GI tract of patients with IBD tend to have an increase in nitrogen oxide synthase expression, which has been linked to the increase of reactive oxygen species (13).
Reactive oxygen species, such as peroxide and superoxide, are known as carcinogens as they cause oxidative stress in cells leading to apoptosis as well as damage to DNA, proteins, and lipids. This damage can then manifest into mutations such as the loss of function of p53, a known tumor suppressor, leading to cancer cell formation (13).
Since there is an increased risk of CRC in IBD patients, surveillance and screening is important to try and identify potential cancer hotspots before they develop. Creating an optimal surveillance schedule can be difficult as it varies case by case.
This is due to the difficulty of screening nonpolypoid (flat or slightly elevated) lesions, the unpredictable rate of development from dysplasia (abnormal growth) to CRC, and the sensitivity available for detecting dysplasia compared to the risk and cost of constant colonoscopies (13). Most international guidelines suggest that screening should begin approximately 8 years after the onset of the symptoms from IBD (15).
There are a lot of criteria that go into how frequently a patient should be screened, but on average this ranges from every 1-5 years in European societies and every 1-3 years in US societies (15). The best way to reduce the risk of developing CRC in IBD patients is through primary prevention techniques.
These techniques include drugs used to manage symptoms, dietary changes/restrictions, lifestyle changes, and improvement of the gut microbiome in patients (15). Pharmaceutical treatments are the most common method of prevention recommended after diagnosis of IBD. The drugs(s) recommended depends on the severity of the disease, and other factors.
The most commonly prescribes drugs include corticosteroids, amino salicylates, antibiotics, anti-inflammatory and immunosuppressive drugs (16). While data shows that many of these drugs can improve the negative symptoms associated with IBDs, they can also have adverse effects on the patient (16).
Another option that can reduce the risk of developing CRC is to surgically remove areas of the colon that are impacted by the disease (16). While these are currently some of the best options to help manage the symptoms of IBD, there are many preventative measures one can take to try and avoid the development of IBD, thus decreasing the risk of CRC.
Promoting Gut Health and Preventing IBD and CRC
According to many research articles surrounding IBD, CRC, and other gut related health issues, there are many things’ people can do now to prevent disease on-set and progression. One key aspect of prevention is a healthy diet full of fiber and prebiotic/probiotic foods (17).
These foods include bananas, cabbage, flax seeds, apples, beans, potatoes, onions, oats, yogurt, kimchi, cheese, kefir, kombucha, avocados, carrots, broccoli, collard greens, and many other fruits and vegetables. In fact, many studies have concluded that a diet that consists of many fruits and vegetables leads to a reduced risk of developing IBD, while diets that consist of mainly animal fats and refined sugar increase the risk of developing IBD (18).
Eating a balanced diet is key to maintaining a healthy gut microbiome, which in turn is responsible for the proper function of many different parts of the human body. Another way to improve gut health and decrease the risk of disease development is through lifestyle modifications such as exercise, stress management, smoking cessation, and more.
A research article from the Gastroenterology Journal by Piovani and others identified environmental factors that could either prevent IBDs or increase the risk of developing IBD (11). The preventive factors identified in the article include “physical activity, breastfeeding, bed sharing, tea consumption, high levels of folate, high levels of vitamin D, and H pylori infection” (11). The article also concluded that “smoking, urban living, appendectomy, tonsillectomy, antibiotic exposure, oral contraceptive use, consumption of soft drinks, vitamin D deficiency, and non-Helicobacter pylori- like enterohepatic Helicobacter species” were linked to an increased risk of IBD.
Future Directions and Research
With increased interest in the gut microbiota in recent years, science has uncovered a better understanding of the importance of a balanced gut microbiome, and ways to improve gut health. As mentioned before, the gut microbiome consists of many different microbes, all of which play a key role in the maintenance of a healthy gut.
Current advancements have been made in understanding the role of the gut microbiome in diseases such as IBD and CRC. While genetic factors play a part in the likelihood of developing one of these conditions, science has uncovered that environmental factors can be responsible for the on-set and progression of these diseases (19).
As mentioned previously, everyday things can impact the gut microbiota in negative or positive ways such as diet, exercise, antibiotic usage, and more. Thanks to this kind of research, there have been promising developments in creating treatments for IBD and CRC. New drugs are being researched that can minimize the inflammation or other negative symptoms from IBD without the negative side effects commonly experienced (20).
These drugs include new anti-TNFs, anti-adhesion biologics, IL-12/IL-23 inhibitors, small-molecule drugs, and more (20). Other research has looked at certain therapies that have the potential to treat or minimize the effects of IBD such as stem-cell transplant or a fecal microbiota transplant (20).
By reducing the amount of inflammation and other side effects of IBD, the risk of developing CRC decreases as well. As science continues to evolve, more research can go into looking at the potential of personalized medicine and targeted therapies based on a patient’s specific needs. The gut microbiome is incredibly diverse, not just in the different types of bacteria, viruses, and eukaryotes, but from person to person as well.
It should be noted that treatments or preventative measures taken for issues pertaining to the gut microbiome should not be looked at as one size fits all. Instead, patients should be treated on a case-by- case basis as certain treatments might not be effective in every patient. Current research is not that advanced, but the future holds a lot of potential for more personalized medicine and therapies.
The gut microbiome has been in the spotlight in recent years and will likely be a hot topic for many years to come due to its impact on human health and wellness. Research continues to show how influential a healthy gut microbiota is on many key aspects of its host such as the development of diseases, the immune system, mental health, metabolism, and more.
As discussed, there are many factors that can impact the health of the gut, and it is up to individuals to prioritizing their gut health through lifestyle modifications such as a good diet, an active lifestyle, not smoking tobacco products, managing stress, ensuring proper vitamin intake, and more.
Prevention is the best medicine, and simple changes today can make for big changes later. Those at risk due to genetics, family history, age, or those who have already been diagnosed with IBD should be sure to keep up with disease screening and surveillance, as early detection for both IBD and CRC is key for the proper management and effective treatment of the diseases.
Research is still underway to try and identify the pathogenesis of IBD and CRC, as well as uncovering the relationship between the gut microbiome in health and disease. With the prevalence of IBD increasing globally, and the low survival rate of those diagnosed with CRC, it is evident that future research is necessary to understand better ways to prevent, diagnose, and treat these diseases of the gut.
1. Ogoburio, I., Gonzales, J., Shumway, K. R., & Tuma, F. (2023, April 8). Physiology, gastrointestinal – statpearls – NCBI bookshelf. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK537103/
2. Dworken, H. J., Hightower, N. C., & Sircus, W. (n.d.). Absorption. Encyclopædia Britannica. https://www.britannica.com/science/human-digestive-system/Absorption
3. Zmora, N., Suez, J., & Elinav, E. (2018, September 27). You are what you eat: Diet, health and the gut microbiota. Nature News. https://www.nature.com/articles/s41575-018-0061-2
4. Mailing, L. J., Allen, J. M., Buford, T. W., Fields, C. J., & Woods, J. A. (2019, April). Exercise and the gut microbiome: A review of the evidence… : Exercise and sport sciences reviews. Exercise and Sport Science Reviews. https://journals.lww.com/acsm- essr/fulltext/2019/04000/Exercise_and_the_Gut_Microbiome__A_Review_of_the.4.aspx?fbclid =IwAR0Q3CTLWukI-pRgi2Owjax9SOWH3dXbeyXrj7aRcu1_XxCRVVP2oNGUGBE
5. Fang, J., Wang, H., Zhou, Y., Zhang, H., Zhou, H., & Zhang, X. (2021, May 17). Slimy Partners: The mucus barrier and gut microbiome in ulcerative colitis. Experimental & molecular medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178360/#:~:text=Dysbiosis%20induces%20im pairment%20of%20the,cell%20depletion%2C%20and%20host%20inflammation
6. Das, B., & Nair, G. B. (2019, September 20). Homeostasis and dysbiosis of the gut microbiome in Health and Disease – Journal of Biosciences. SpringerLink. https://link.springer.com/article/10.1007/s12038-019-9926-y
7. Fakhoury, M., Negrulj, R., Mooranian, A., & Al-Salami, H. (2022, October 5). Full article: Inflammatory bowel disease: Clinical aspects and treatments. Taylor & Francis Online. https://www.tandfonline.com/doi/full/10.2147/JIR.S65979
8. Centers for Disease Control and Prevention. (2022, April 13). What is inflammatory bowel disease (IBD)?. Centers for Disease Control and Prevention. https://www.cdc.gov/ibd/what-is- IBD.htm
9. Caviglia, G. P., Garrone, A., Bertolino, C., Vanni, R., Bretto, E., Poshnjari, A., Tribocco, E., Frara, S., Armandi, A., Astegiano, M., Saracco, G. M., Bertolusso, L., & Ribaldone, D. G. (2023, January 13). Epidemiology of inflammatory bowel diseases: A population study in a healthcare district of north-west italy. Journal of clinical medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860659/
10. Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Phil, W. T., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J. C., Chan, F. K., Sung, J. J., & Kaplan, G. G. (2018). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st Century: A systematic review of population-based studies. Lancet (London, England). https://pubmed.ncbi.nlm.nih.gov/29050646/
11. Piovani, D., Danese, S., Peyrin-Biroulet, L., Nikolopoulos, G. K., Lytras, T., & Bonovas, S. (2019, April 20). Environmental risk factors for inflammatory bowel diseases: An umbrella review of Meta-analyses. Gastroenterology. https://www.sciencedirect.com/science/article/pii/S0016508519367095?casa_token=OgP7wDN qFdUAAAAA%3AC97djXkQDrelCrkPxhWgmicCjf_OGvlo3t_e31eokyJOGq3DLGq20Q0vpmJmYwyi qU-jL40
12. Rubin, D. C., Shaker, A., & Levin, M. S. (2012, May 8). Chronic intestinal inflammation: Inflammatory bowel disease and colitis-associated colon cancer. Frontiers in immunology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347037/
13. Stidham, R. W., & Higgins, P. D. R. (2018, April 1). Colorectal cancer in inflammatory bowel disease. Clinics in Colon and Rectal Surgery. https://www.thieme- connect.com/products/ejournals/html/10.1055/s-0037-1602237
14. Grivennikov, S. I., Greten, F. R., & Karin, M. (2010, March 19). Immunity, Inflammation, and Cancer. Cell. https://www.cell.com/fulltext/S0092-8674(10)00060-7?large_figure=true
15. Marabotto, E., Kayali, S., Buccilli, S., Levo, F., Bodini, G., Giannini, E. G., Savarino, V., & Savarino, E. V. (2022, August 31). Colorectal cancer in inflammatory bowel diseases: Epidemiology and prevention: A Review. MDPI. https://www.mdpi.com/2072-6694/14/17/4254
16. Seyedian, S. S., Nokhostin, F., & Malamir, M. D. (2019, April-June). A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. Journal of medicine and life. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685307/
17. Martyniak, A., Medyńska-Przęczek, A., Wędrychowicz, A., Skoczeń, S., & Tomasik, P. J. (2021, December 18). Prebiotics, probiotics, synbiotics, paraprobiotics and postbiotic compounds in IBD. MDPI. https://www.mdpi.com/2218-273X/11/12/1903
18. Pigneur, B., & Ruemmele, F. M. (2019, November 25). Nutritional interventions for the treatment of IBD: Current evidence and controversies. Therapeutic advances in gastroenterology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878599/#:~:text=Several%20large%20longitu dinal%20studies%20have,with%20an%20increased%20IBD%20risk
19. Gomaa, E. Z. (2020, November 2). Human gut microbiota/microbiome in health and diseases: A review – antonie van leeuwenhoek. SpringerLink. https://link.springer.com/article/10.1007/s10482-020-01474-7
20. Hazel, K., & O’Connor, A. (2020, February 5). Emerging treatments for inflammatory bowel disease – sage journals. Sage Journals. https://journals.sagepub.com/doi/10.1177/2040622319899297