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Inflammatory Bowel Disease: Causes and Solutions

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Inflammatory bowel disease (IBD) includes disorders characterized by chronic inflammation in all or part of the gastrointestinal (GI) tract. Crohn’s disease and ulcerative colitis (UC) are the primary types of IBD, and recent reports indicate that the United States has had the highest prevalence rate globally, with nearly a quarter of the total patients with IBD living in the US as of 2017.1

IBD: Disease Burden & Impacted Populations

Data from 2015 estimated that three million US adults were diagnosed with either Crohn’s disease or UC.2 Of those diagnosed, approximately one in four experienced financial hardship due to medical bills, and one in six reported cost-related medication nonadherence.3 Recent studies also report that the population demographics of IBD in the US are changing.4 A 2021 cohort study found that prevalence of IBD within Hispanic communities is potentially higher than previously recognized.5 In addition, analysis of 2001 to 2018 Medicare data indicated that while prevalence of IBD increased among all race and ethnicity groups, the highest percentage increase was among Black adults.6

The disease burden associated with IBD may also be measured by the striking number of increased comorbidity risks. Several meta-analyses published in the year 2021 alone suggest that an IBD diagnosis may be associated with an increased risk of heart disease,7 stroke,8 diabetes,7 cancers in the lower GI tract,9 anxiety and depression,10 and periodontitis.11 In addition, results from other recent studies have suggested that compared to controls, patients with IBD showed a significant increased risk of dementia development12 and reduced autonomic nervous system functioning.13 While the main causes of IBD are not fully understood, the interaction between the immune system, genetics, and environmental factors may underlie disease development.14,15 Understanding the potential etiologies, manifestations, and pathogenesis of inflammatory bowel disease may help to personalize and focus effective treatment interventions.

In the following video, Dawn Beaulieu, MD, discusses the functional medicine approach to IBD:

Caption: Dr. Dawn Beaulieu is board certified in internal medicine and gastroenterology, with an expertise in the field of inflammatory bowel disease. She has been caring for patients at Vanderbilt since 2009 and is part of the multi-disciplinary team at the Vanderbilt IBD center.

Crohn’s Disease & Ulcerative Colitis: A Deeper Dive

Both Crohn’s disease and UC lead to digestive disorders and chronic inflammation in the digestive system, resulting in some similar symptoms. Yet there are fundamental differences between the two diseases, including the following:

  • GI location: Crohn’s disease most often affects the intestinal walls (lower small intestine and large intestine) but can occur anywhere along the GI tract at any layer.14 UC only affects the mucosal layers of the colon, where the inflammation usually causes ulcers to develop.14
  • Symptoms: Both conditions share primary symptoms such as pain, diarrhea, fever, fatigue, and weight loss. Distinguishing symptoms may include malnutrition for Crohn’s disease due to potential damage of the small intestine and rectal bleeding for UC. While blood in the stool may still be seen with Crohn’s disease, it is less common.14 Also of note, abdominal pain experienced by patients with UC may be more intermittent and associated with bowel movements, while abdominal pain from Crohn’s disease may be associated with problems such as fistula and rectal lesions.14

Westernization, characterized by an urban lifestyle, increased exposure to pollution, change in diet, access to antibiotics, and better hygiene, may be associated with Crohn’s disease and UC development.16,17 Specific to Crohn’s disease, a 2020 systematic review was the first to investigate the disease’s relationship with environmental toxins.18 Investigators noted that while the included research studies demonstrated some inconsistent methodologies and conflicting results, metals and endocrine disruptors surfaced as potential candidates that may contribute to the pathogenesis of Crohn’s disease.18 Recent reports on UC continue to also highlight the genetic influence on disease development, suggesting that those genes common in UC sufferers may implicate epithelial dysfunction and mitochondrial disease and may play a role in UC pathogenesis.16

Standard Care & Complimentary Treatments: A Focus on Recent Studies

Treatment recommendations for Crohn’s disease and UC from the American College of Gastroenterology (ACG) clinical guidelines range from pharmaceutical to potential surgical approaches based upon specific diagnosis and level of disease activity.19,20 In addition to controlling primary disease symptoms, both guidelines emphasize the therapeutic goals of reducing inflammation and achieving mucosal healing. Specific to Crohn’s disease, the 2018 ACG guidelines also recommend the assessment and management of stress, depression, and anxiety as part of comprehensive care and note that dietary interventions may be appropriate adjunct therapies, especially with initial treatments.19

Research studies over the years have suggested many therapeutic agents for the improvement of IBD. Dietary modifications such as prioritizing fruits, vegetables, and fiber continue to surface in studies as promising approaches for IBD treatment that help to reduce intestinal inflammation and permeability.21 And some of the specific dietary components and nutritional supplements highlighted for their potential benefit in both the prevention and treatment of IBD include phytonutrients, fatty acids, amino acids, bioactive peptides, anti-inflammatory spices and herbs, prebiotics, and probiotics.22-24 The most recent research continues to support the highlighted benefits of plant-based compounds and dietary supplements for IBD treatment:

  • A 2021 meta-analysis of 38 randomized controlled trials (RCTs) explored the clinical effects and microbiota changes associated with using probiotics, prebiotics, and synbiotics for IBD treatment and found that all induced or maintained IBD’s remission and specifically reduced UC disease activity.25 Researchers further suggested that supplements based on Lactobacillus and Bifidobacterium or more than one strain may be more beneficial for IBD remission, and a probiotic dosage of 1010-1012CFU/day may be an appropriate reference range.25
  • Two smaller RCTs investigated the effect of dietary saffron and flaxseed on inflammation and severity of disease in UC patients.26-27 In one RCT (n=80), the intervention group received 100 mg of saffron daily for eight weeks, and results suggested that compared to placebo, dietary saffron may improve antioxidant factors and reduce UC disease severity.26 In the other RCT (n=90), the intervention groups received either ground flaxseed (30 gm/day) or flaxseed oil (10 gm/day) for 12 weeks, and results suggested that compared to the control group, those receiving either form of flaxseed supplementation showed reduced inflammatory biomarkers and reported significantly higher quality of life.27

While the 2019 ACG clinical guidelines for UC states that fecal microbiota transplantation (FMT) requires more study and clarification before becoming a recommended UC therapy,20 FMT has been found in some studies to be a viable potential treatment approach for patients with IBD. As a recent example, a 2020 meta-analysis of 36 studies found that FMT used for management of IBD demonstrated a response rate of 54%, with complete remission of 37%.28 The researchers in this meta-analysis noted that patients diagnosed with Crohn’s disease appeared to benefit more from the procedure than other types of IBD.28

Research continues to uncover potential IBD etiologies and determine the most effective lifestyle-based treatment and prevention strategies. At IFM’s GI Advanced Practice Module (APM), hear from experts in the field about the latest research as well as how those therapeutic agents most often used and effective in IBD treatment help to restore optimal GI balance. In addition, learn more about how the DIGIN model and IFM’s 5R framework help to personalize IBD treatments.

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References

  1. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):17-30. doi:1016/S2468-1253(19)30333-4
  2. National Center for Chronic Disease Prevention and Health Promotion. Inflammatory bowel disease (IBD): data and statistics. Centers for Disease Control and Prevention. Updated April 14, 2022. Accessed August 16, 2023. https://www.cdc.gov/ibd/data-statistics.htm
  3. Nguyen NH, Khera R, Dulai PS, et al. National estimates of financial hardship from medical bills and cost-related medication nonadherence in patients with inflammatory bowel diseases in the United States. Inflamm Bowel Dis. 2021;27(7):1068-1078. doi:10.1093/ibd/izaa266
  4. Barnes EL, Loftus EV Jr, Kappelman MD. Effects of race and ethnicity on diagnosis and management of inflammatory bowel diseases. Gastroenterology. 2021;160(3):677-689. doi:10.1053/j.gastro.2020.08.064
  5. Zhornitskiy A, Shen S, Le LB, et al. Rates of inflammatory bowel disease in Hispanics comparable to non-Hispanic Whites: results of a cohort study. Int J Colorectal Dis. 2021;36(5):1043-1051. doi:10.1007/s00384-020-03819-0
  6. Xu F, Carlson SA, Liu Y, Greenlund KJ. Prevalence of inflammatory bowel disease among Medicare fee-for-service beneficiaries – United States, 2001-2018. MMWR Morb Mortal Wkly Rep. 2021;70(19):698-701. doi:10.15585/mmwr.mm7019a2
  7. Li Z, Qiao L, Yun X, Du F, Xing S, Yang M. Increased risk of ischemic heart disease and diabetes in inflammatory bowel disease. Z Gastroenterol. 2021;59(2):117-124. doi:10.1055/a-1283-6966
  8. Chen Y, Wang X. Increased risk of stroke among patients with inflammatory bowel disease: a PRISMA-compliant meta-analysis. Brain Behav. 2021;11(6):E2159. doi:10.1002/brb3.2159
  9. Wan Q, Zhao R, Xia L, et al. Inflammatory bowel disease and risk of gastric, small bowel and colorectal cancer: a meta-analysis of 26 observational studies. J Cancer Res Clin Oncol. 2021;147(4):1077-1087. doi:10.1007/s00432-020-03496-0
  10.  Barberio B, Zamani M, Black CJ, Savarino EV, Ford AC. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(5):359-370. doi:10.1016/S2468-1253(21)00014-5
  11.  Zhang Y, Qiao D, Chen R, Zhu F, Gong J, Yan F. The association between periodontitis and inflammatory bowel disease: a systematic review and meta-analysis. Biomed Res Int. 2021;2021:6692420. doi:10.1155/2021/6692420
  12.  Zhang B, Wang HE, Bai Y-M, et al. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut. 2021;70(1):85-91. doi:10.1136/gutjnl-2020-320789
  13.  Kim K-N, Yao Y, Ju S-Y. Heart rate variability and inflammatory bowel disease in humans: a systematic review and meta-analysis. Medicine (Baltimore). 2020;99(48):E23430. doi:10.1097/MD.0000000000023430
  14.  Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life. 2019;12(2):113-122. doi:10.25122/jml-2018-0075
  15.  Fathollahi A, Aslani S, Mostafaei S, Rezaei N, Mahmoudi M. The role of killer-cell immunoglobulin-like receptor (KIR) genes in susceptibility to inflammatory bowel disease: systematic review and meta-analysis. Inflamm Res. 2018;67(9):727-736. doi:10.1007/s00011-018-1162-7
  16.  Porter RJ, Kalla R, Ho G-T. Ulcerative colitis: recent advances in the understanding of disease pathogenesis. F1000Res. 2020;9:F1000 Faculty Rev-294. doi:10.12688/f1000research.20805.1
  17.  Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769-2778. doi:10.1016/S0140-6736(17)32448-0
  18.  Tenailleau QM, Lanier C, Gower-Rousseau C, Cuny D, Deram A, Occelli F. Crohn’s disease and environmental contamination: current challenges and perspectives in exposure evaluation. Environ Pollut. 2020;263(Pt B):114599. doi:10.1016/j.envpol.2020.114599
  19.  Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113(4):481-517. doi:10.1038/ajg.2018.27
  20.  Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384-413. doi:10.14309/ajg.0000000000000152
  21.  Shin DW, Lim BO. Nutritional interventions using functional foods and nutraceuticals to improve inflammatory bowel disease. J Med Food. 2020;23(11):1136-1145. doi:10.1089/jmf.2020.4712
  22.  Larussa T, Imeneo M, Luzza F. Potential role of nutraceutical compounds in inflammatory bowel disease. World J Gastroenterol. 2017;23(14):2483. doi:10.3748/wjg.v23.i14.2483
  23.  Saxena A, Kaur K, Hegde S, Kalekhan FM, Baliga MS, Fayad R. Dietary agents and phytochemicals in the prevention and treatment of experimental ulcerative colitis. J Tradit Complement Med. 2014;4(4):203-217. doi:10.4103/2225-4110.139111
  24.  Hossen I, Hua W, Ting L, et al. Phytochemicals and inflammatory bowel disease: a review. Crit Rev Food Sci Nutr. 2020;60(8):1321-1345. doi:10.1080/10408398.2019.1570913
  25.  Zhang X-F, Guan X-X, Tang Y-J, et al. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Nutr. 2020;60(5):2855-2875. doi:10.1007/s00394-021-02503-5
  26.  Tahvilian N, Masoodi M, Faghihi Kashani A, et al. Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: a randomized, double-blind, placebo-controlled study. Phytother Res. 2021;35(2):946-953. doi:10.1002/ptr.6848
  27.  Morshedzadeh N, Shahrokh S, Chaleshi V, Karimi S, Mirmiran P, Zali MR. The effects of flaxseed supplementation on gene expression and inflammation in ulcerative colitis patients: an open-labelled randomised controlled trial. Int J Clin Pract. 2021;75(5):e14035. doi:10.1111/ijcp.14035
  28.  Caldeira LF, Borba HH, Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Fecal microbiota transplantation in inflammatory bowel disease patients: a systematic review and meta-analysis. PLoS One. 2020;15(9):E238910. doi:10.1371/journal.pone.0238910

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