Modulation of the gut microbiome can reverse inflammatory bowel disease states

Modulation of the gut microbiome can reverse inflammatory bowel disease states
Margo R. Flanagan
American College of Healthcare Sciences

Abstract
Five million people worldwide, including one million Americans are affected by inflammatory bowel diseases such as ulcerative colitis and Crohn’s. Dysbiosis of the microbial communities in the digestive system is implicated in the development of diseases and cancer (Carding, Verbeke, Vipond, Corfe & Owne, 2015). Research on the effects of nutrition on gut bacteria, vitamin D, factors contributing to defects in digestive lining and therapeutic treatments show promising evidence that modulation of the gut microbiome can reverse inflammatory bowel disease states.

Keywords: inflammatory bowel disease, microbiota, microbiome, autoimmunity, nutrition

Introduction
In the last decade, research has explored the area of the human microbiota, the gut microbiome and its dynamic interaction with the immune system. Dysbiosis of the microbiota is implicated as the cause of Autoimmune disease and when affecting the digestive system development of inflammatory bowel disease states occur (Carding, Verbeke, Vipond, Corfe & Owen, 2015).
Clinical treatment of IBD with immunosuppressants occurs when the symptoms have progressed to a systemic problem and quality of life has diminished. A rising incidence of chronic disease seen all over the world warrants a hard look into the research at the inter-relationships between nutrition, immune system function, the gut microbiome and its ability to reverse IBD states. Promising evidence suggests that modulation of the gut microbiota can balance the immune system and reverse the symptoms of inflammatory bowel disease.

Methods and Results
Google scholar searches were performed utilizing key words inflammatory bowel disease, microbiota, microbiome, autoimmunity, nutrition, leaky gut and dysbiosis. Journal articles were restricted to last decade.

Dysbiosis
The microbiome, a factor related to the human genome is the symbiotic relationship between microorganisms and the host of their environment. When the microorganisms residing in the digestive system, the gut microbiota are disrupted through a host of chemical, environmental and genetic factors dysbiosis occurs. Dysbiosis resulting from an overgrowth of Candida species is implicated in the onset of Celiac and Crohn’s disease as well as the cause of polysomatic symptoms seen in fibromyalgia, irritable bowel syndrome and chronic fatigue sydrome (Olmstead, Meiss & Ralston, 2012). The microbial communities living within the mucosal lining of the digestive tract in individuals with Crohn’s and Celiac show distinct decreases in Firmicutes, Erysipelotrichales, Bacteroidales and increases in Enterobacteriaceae , Pasteurellaceae and Fusobacteriaceae when compared to healthy controls (Carding, Verbeke, Vipond, Corfe & Owen, 2015).
Effects of Nutrition on Gut
The gut microbiota’s structure and function is largely shaped by the diet consumed requiring the help of the gut microbiota. A healthy digestive system has a predominance of Bacteroides spp that cleave the glycosidic linkages of plant cell wall glycans through fermentation into short chain fatty acids (SCFAs) (Koropatkin, Cameron & Martens, 2012). SCFAs contribute to a healthy immune system by promoting mucosal lining integrity and barrier function, reduction of inflammatory mediators, proliferation of gut friendly bacteria and serve as energy for colonocytes and gut epithelial cells (Kau, Ahern, Griffin, Goodman & Gordon, 2011).
Digestive Immune System
Within the digestive system of healthy individuals, homeostasis consists of a balanced microbial community within an intact mucosal lining acting as a barrier against the immune system. Permeations in the digestive wall cause “leaky gut” and material crossing through activate the adaptive and innate immune systems, cause autophagy and stimulate an inflammatory response (Vindigni, Zisman, Suskind & Damman, 2016). Dysfunction of the mucosal lining of CD patients is apparent in genetic studies with detection of disease specific autoantibodies (Campbell, 2013).
Low levels of vitamin D are frequently seen in and considered a risk factor for the development of IBD. Experimental animal models with vitamin d deficiency show advanced disease states of IBD. Without vitamin d, regulation of T cell development malfunctions leading to inflammation in the gut and dysbiosis (Cantora, McDaniel, Bora, Chen & James, 2014).
Leptin regulates the appetite, regulates T cells and promotes the release of cytokines at can either suppress or regulate inflammatory immune response in the gut. Decreased amounts of leptin are in proportion to increased destruction of intestinal lining from inflammation with increased mortality (Kau, et al, 2011).
Therapeutic and Alternative Therapies
Vitamin D can reduce the production of inflammatory mediators in the digestive tract such as tumor necrosis factor. 5,000 IU of vitamin D per day can reduce the symptoms of CD (“Vitamin D Council, 2015).
A study on barrier function of colonic epithelial cells affected by tumor necrosis factor demonstrated the ability of Boswellia serrata to reduce the inflammatory response. Acetyl-11-keto-b-Boswellic acid (AKBA) maintained the integrity of the epithelium barrier, exhibited strong antioxidant activity and reduced the activity of inflammatory mediators (Catanzano et al., 2015).
McCarville, Caminero and Verdu (2016) highlight multiple studies of immune response to different bacterial populations. T-cell maintenance and homeostasis, dendritic cells and intestinal barrier function and permeability is directly affected by overgrowth of disease promoting bacterial populations unable to cleave the glycosidic linkages of SCFAs. Diet was demonstrated in human studies to cause quick changes in the gastrointestinal tract when the right foods were eaten, modulate the gut microbiota reduce pro-inflammatory cytokines and improve intestinal barrier function.
Mullin, Turnbull and Rampertab (2009) explored a large number of clinical trials showing promising evidence of pre and probiotics and supplement improvement in health and reductions in disease severity. Aloe vera was superior to placebo in moderately active ulcerative colitis, wheat grass reduced the “clinical disease activity index” and rectal bleeding, Boswellia serrata showed a 70% remission in patients with moderate ulcerative colitis when compared to conventional therapy, curcumin vs placebo improved the rate of relapse and fish oil reduced the rate of relapse vs control group while also preventing colitis in in vivo and in vitro studies.

Discussion
Chronic diseases are a clinical challenge due to their unknown etiology, vast array of symptoms and hardship in managing symptoms. Inflammatory bowel disease is chronic, unremitting and greatly decreases quality of life. Dysbiosis, a pathological threat to health is implicated as the trigger for allergies, asthma and also IBD. It has been demonstrated within gnotobiotic animal research models that dysbiosis of the gut microbiota leads to inflammatory bowel disease states. Furthermore, modulation of the microbiota through pre and probiotics, proper nutrition and stress reduction enhance mucosal barrier and immune system function.
Gut integrity through reduction of inflammation is the best approach to reversing IBD. A healthy gut equates to a balanced microbiota, healthy nutritional status and proper immune function. Dysbiosis in the gut leads creates a chronic inflammatory environment leaving the immune system malfunctioning while trying to heal itself. This cycle of imbalance leads to pathological conditions. Without beneficial bacteria and nutritional support from plant fiber, the gut is unable to mediate a proper immune response or promote intestinal barrier function. Barrier function is returned when inflammatory mediators are removed and the gut microbiota includes proper microbial communities.
Conclusion and Recommendations
Currently there is no curative treatment for inflammatory bowel diseases. Modern treatments consist of suppressing the immune system and the hallmark symptom of IBD, inflammation while also treating the symptoms of the disease. Nutritional support that seeks to balance the microbiota shows promising and effective results in animal models but is lacking in human clinical trials. Long range studies on the impact of diet and nutrition in individuals with IBD are warranted. Changing the diet is the easiest way to promote positive changes in health.
Prevention of IBD is the best course of therapy as with most chronic diseases but when the disease has already progessed a diet that includes prebiotic organic plant fiber, fermented foods and supplementation with probiotics, Boswellia serrata, curcumin, vitamin d and fish oils should be the standard course of treatment over immunosuppressants and pharmaceuticals. Modulation of the gut microbiota balances the immune system response, decreases proinflammatory cytokines and subsequent tissue damage of the intestinal epithelial mucosal barrier.
Leaky gut syndrome lacks a specific confirmatory test. Individuals with confirmed leaky gut syndrome with development of autoimmune disease should be explored given that the 80% of the lymphatic immune system resides in the digestive tract. Data collected could entail a standard preventative nutritional program for those likely to develop IBD. Leaky gut syndrome has the potential to be resolved before triggering chronic disease.

References
Campbell, A. (2014). Autoimmunity and the Gut. Autoimmune Diseases, 2014, pp.1-12.
Cantorna, M., McDaniel, K., Bora, S., Chen, J. and James, J. (2017). Vitamin D, immune regulation, the microbiota, and inflammatory bowel diseaseExperimental Biology and Medicine -Margherita T Cantorna, Kaitlin McDaniel, Stephanie Bora, Jing Chen, Jamaal James, 2014. Experimental Biology and Medicine.Available at: http://journals.sagepub.com/doi/pdf/10.1177/1535370214523890
Carding, S., Verbeke, K., Vipond, D., Corfe, B. and Owen, L. (2015). Dysbiosis of the gut microbiota in disease. Microbial Ecology in Health & Disease, 26(0).
Catanzaro, D., Rancan, S., Orso, G., Dall’Acqua, S., Brun, P., Giron, M., Carrara, M.,
Castagliuolo, I., Ragazzi, E., Caparrotta, L. and Montopoli, M. (2015). Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage. PLOS ONE, 10(5), p.e0125375.
McCarville, J., Caminero, A. and Verdu, E. (2016). Novel perspectives on therapeutic modulation of the gut microbiotaTherapeutic Advances in Gastroenterology – 2016. Therapeutic Advances in Gastroenterology. [online] Available at:http://journals.sagepub.com/doi/full/10.1177/1756283X16637819.
Mullin, G., Turnbull, L. and Rampertab, D. (2009). Supplements for Inflammatory Bowel Disease – Integrative Practitioner. [online] Integrative Practitioner. Available at:http://www.integrativepractitioner.com/topics/digestive-health/supplements-for-inflammatory-bowel-disease/.
Kau, A., Ahern, P., Griffin, N., Goodman, A. and Gordon, J. (2011). Human nutrition, the gut microbiome and the immune system. Nature, 474(7351), pp.327-336.
Olmstead, S., Meiss, D. and Ralston, J. (2012). Candida, Fungal-Type Dysbiosis, and Chronic Disease (June 2012) Townsend Letter for Doctors & Patients. [online] Townsendletter.com. Available at: http://www.townsendletter.com/June2012/candida0612.html
Vindigni, S., Zisman, T., Suskind, D. and Damman, C. (2017). The intestinal microbiome,barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directionsTherapeutic Advances in Gastroenterology -. Therapeutic Advances in Gastroenterology. [online] Available at: http://journals.sagepub.com/doi/abs/10.1177/1756283X16644242
Vitamindcouncil.org. (2017). Vitamin D Council | Vitamin D and inflammatory bowel disease. [online] Available at: https://www.vitamindcouncil.org/health-conditions/inflammatory-bowel-disease/

 

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