Inflammatory Bowel Disease: The What, Why, And How

Welcome to my blog entitled ‘Inflammatory Bowel Disease: The What, Why and How’.

Before we start, other blogs that you might be interested in, include:

• The Ultimate Guide To IBS
• SIBO: What Causes It
• Can the gut microbiome cause depression and changes in mood?

What Is Inflammatory Bowel Disease (IBD)?

IBD, including Crohn’s disease and ulcerative colitis, is characterised by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalysed by the genetic susceptibility of the individual.

Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses (1).

What Causes Inflammatory Bowel Disease (IBD)?

A large number of environmental factors are considered risk factors for IBD, including:

• Smoking
• Diet
• Drugs
• Geography
• Social and psychological stress

Let’s look at these in a little more detail:

Smoking: Among them, smoking remains the most widely studied and replicated environmental prompter for IBD.

Diet: An excessive consumption of sugar, animal fat and linoleic acid is considered a risk factor for IBD development, whereas a high fiber diet and citrus fruit consumption may play a protective role.

Drugs: The effect of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) in the gastrointestinal tract is well recognised. However, limited high quality evidence is available to support the notion that aspirin and NSAIDs have an effect in triggering onset or relapse of IBD. Ananthakrishnan et al found no association between the dose, duration, or frequency of aspirin use and the risk for CD or UC; but the high dose, prolonged using duration, and frequent use of NSAIDs had been associated with an increased risk of CD and UC.

A recent study has found that the use of antibiotics is an important environmental factor, influencing the risk of IBD through their effect on the microbiome. Antibiotic use within the first year of life is more common among pediatric IBD cases compared to controls (1).

Geography: Recent ecological and epidemiologic evidence suggests that air pollution may contribute to the risk of CD and UC. The rising incidence of CD and UC in developing countries parallels the development of industrialisation (1). Also, recent literature suggests that the role of vitamin D is multifarious and associated with diverse diseases including IBD. Leslie et al found that vitamin D deficiency had been common in diagnosed IBD patients and pointed out that low vitamin D had contributed to the increased risk of IBD.

Both diseases are more often diagnosed in urban areas compared to rural areas

Stress: Stress has long been proposed to play a role in the pathogenesis of CD and UC. Bitton et al suggested that individuals with lower levels of stress had a reduced risk of the disease onset. Mood components of perceived stress, including depression and anxiety, may play a strong role in mediating the deterioration of IBD (1).

The Microbiome And Inflammatory Bowel Disease (IBD)

Many studies have examined the gut flora in CD and UC in both inflamed and non-inflamed segments, and found that there is a significantly reduced biodiversity in faecal microbiome in IBD patients compared to that in healthy controls. Other research has also found that the microbiome in IBD patients is more unstable than that in healthy individual.

In healthy intestine, the Firmicutes and Bacteroidetes phyla predominate, and contribute to the production of epithelial metabolic substrates. In contrast, the microbiome is characterised by a relative lack of Firmicutes and Bacteroidetes, and an over-representation of enterobacteria in CD; meanwhile, a reduction in Clostridium spp. and an increase in E. coli have been reported in UC (1).

Leaky Gut And Inflammatory Bowel Disease (IBD)

Defective epithelial barrier and increased intestinal permeability (i.e leaky gut) have long been observed in IBD patients. The first physical barrier that intestinal bacteria and food antigens encounter on the mucosal surface is represented by the mucous layer that covers the gut lining.

The second line of defense against bacterial invasion is formed by the intestinal epithelium which consists of enterocytes and specialised cells, such as goblet cells and Paneth cells. Besides forming a physical barrier against bacteria, these cells can secrete a number of antimicrobial proteins. Defective expression of antimicrobial proteins has been observed in patients with CD (1).

Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction (17)

Children And Inflammatory Bowel Disease (IBD)

Although children can present with the classic symptoms of weight loss, abdominal pain, and bloody diarrhea, many present with nonclassic symptoms of isolated poor growth, anemia, or other extraintestinal manifestations.

Psoriasis And Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease (IBD) and psoriasis (PS) are associated conditions. The reason for this association lies in the sharing of predisposition genes and common immunological mechanisms (10).

The gut microbiome seems relevant in both conditions: a reduction of beneficial bacteria has been observed. IBD and PS have in common some comorbidities like cardiovascular disease, similar risk of cancer and psychiatric problems.

Hydrogen Sulfide And Inflammatory Bowel Disease

Studies have proposed that hydrogen sulfide contributes to the pathogenesis of UC by inhibiting butyrate oxidation in colonocytes and/or impairing the intestinal barrier function by reducing the disulfide bonds of the mucus layer, which increases intestinal permeability to enteric pathogens.

Nutrition And Inflammatory Bowel Disease

Dietary fats have also been implicated in the pathogen- esis of IBD, especially polyunsaturated fatty acids (PUFAs). In the Western diet, there is a high omega-6 PUFA to omega-3 fat ratio. Omega-6 fats, which include linoleic acid and arachidonic acid, have been suggested to be pro-inflammatory, whereas n-3 PUFAs, particularly eicosapentaenoic acid and docosahexaenoic acid, which are major component of omega-3 fish oil, are suggested to be anti-inflammatory (13).

Omega-3 PUFAs have been shown to have beneficial effects in other inflammatory conditions such as asthma and rheumatoid arthritis.

Emulsifiers have gained increasing attention as pro-inflammatory food additives that may have a contributory role in the pathogenesis of IBD.30 Emulsifiers are food additives commonly used to give food products a smooth texture, prevent separation, and extend shelf-life. Some common foods that contain emulsifiers include ice cream, non-dairy milk alternatives, salad dressing, and pasta, to name a few. While there are many different emulsifiers used in the food industry, carrageenan, carboxymethylcellulose (CMC), and polysorbate-80 (P80) have been strongly implicated in promoting intestinal inflammation. The majority of the research on emulsifiers and enteric inflammation has been in animal models (13).

The data have suggested that emulsifiers exert their inflammatory effects by altering the gut microbiome through decreasing diversity and promoting pro-inflammatory enteric bacteria.

Dietary Fibre: Whereas meat, dietary fats, and emulsifiers offer a glimpse into how diet can contribute to IBD, fiber has been pro- posed as protective of developing IBD. Fiber has always been regarded as having numerous health benefits but is severely lacking in the typical Western diet. In terms of inflammation, fiber is hypothesized to exert its anti-inflammatory effects via metabolization by intestinal bacteria to short chain fatty acids (SCFAs), and play a role in maintaining intestinal barrier func- tion. In a systematic review of the literature, Hou et al generally found that both retrospective and prospective studies observed that high intake of dietary fiber was associated with decreased risk of UC and CD – but only 1 study found a statistically significant reduced risk in CD (13).

In a large prospective study using the Nurses’ Health study, Ananthakirshnan et al found higher intake of dietary fiber was associated with a lower risk of CD but not UC.

Diet And Inflammatory Bowel Disease

There are multiple diets that have been implicated in IBD treatment with varying degrees of quality of data to support their use (13). These include:

• Specific carbohydrate diet
• Low FODMAP diet
• Paleo
• Mediteranean
• Semi-vegetarian

A paper in 2018 claims the Mediterranean diet is the most evidenced diet in the prevention and treatment of IBD.

Supplements And Inflammatory Bowel Disease

Curcumin: It is worth noting curcumin, which is a naturally occurring substance found in turmeric, might be a promising dietary agent for treating IBD via its action on NF-κB. Current data have found 2 to 3 g daily in combination with 5-aminosalicylate is effective in inducing and maintaining remission in mild to moderate UC. Another study found curcumin resulted in clinical and endoscopic improvement in patients with active CD (13).

Probiotics: The use of probiotics seems to be a very promising therapeutic strategy. According to the literature, probiotic bacteria can affect all aspects of IBD pathoetiology, and can fulfil a protective function for the patient. It is necessary to know their path of action and all their properties. It should be noted that many of the publications are based on the animal model of the IBD (16).

Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction.

It’s worth highlighting that restoring normal levels of the selected micronutrients requires elevated doses to compensate for defects in absorptive or signalling mechanisms (19).

Butyrate: Short chain fatty acids (SCFA), such as butyrate, are important metabolites in maintaining intestinal homeostasis. Certain bacteria are capable of producing butyrate via the fermentation of dietary fibre. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions.

A very interesting paper published in 2020 concluded: “We provide evidence that the response to butyrate is not intrinsically altered in IBD patients. However, TNFα renders the epithelium less responsive to this metabolite, defeating the purpose of butyrate supplementation during active inflammation.” (22)

Soluble Fibre: soluble fiber is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects (23).

Omega 3: Omega-3 polyunsaturated fatty acids have been associated with attenuation of the inflammatory responses in IBD, possibly acting as substrates for anti-inflammatory eicosanoid production, similar to prostaglandins and leukotrienes. Omega 3 also act as substrates for the synthesis of resolvins, maresins and protectins, indispensable in resolving inflammation processes. These acids may influence the development or course of IBD by:

• Reducing oxidative stress
• Production of tumour necrosis factor-α and pro-inflammatory cytokines
• Working as chemopreventive agents
• Decreasing the expression of adhesion molecules.

There are numerous controversies in the literature on the effects of ω3FA in the prevention or treatment of IBD, but their effects in reducing inflammation is incontestable.

Conclusion

There is no doubt that an unprecedented progress in our understanding of IBD pathogenesis has been achieved during the past few years. The key factors responsible for IBD include genetic components, environmental elements, microbial flora and immune responses. It is hard to dispute the popular belief that IBD arises from an extremely complex interaction among genetic and environmental elements, dysregulated immune responses and alterations of the microbiome, and that none of these factors alone is likely to cause the disease (1).

References

1. Inflammatory bowel disease: pathogenesis: click here.
2. Inflammatory Bowel Disease Presentation and Diagnosis: click here.
3. Inflammatory Bowel Disease in Children and Adolescents: click here.
4. Early-Onset Inflammatory Bowel Disease: click here.
5. Unravelling the pathogenesis of inflammatory bowel disease: click here.
6. Inflammatory Bowel Disease in Primary Immunodeficiencies: click here.
7. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease: click here.
8. Inflammatory bowel disease: click here.
9. Management of inflammatory bowel disease: click here.
10. Psoriasis and Inflammatory Bowel Disease: click here.
11. Hypoxia and inflammatory bowel disease: click here.
12. The Gut Microbiota in Inflammatory Bowel Disease: click here.
13. Dining With Inflammatory Bowel Disease: A Review of the Literature on Diet in the Pathogenesis and Management of IBD: click here.
14. The Role of Diet in Inflammatory Bowel Disease: click here.
15. Role of autophagy in the pathogenesis of inflammatory bowel disease: click here.
16. The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)-A Critical Review: click here.
17. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut: click here.
18. The role of diet in the prevention and treatment of Inflammatory Bowel Diseases: click here.
19. Vitamins and Minerals in Inflammatory Bowel Disease: click here.
20. Diet and nutritional factors in inflammatory bowel diseases: click here
21. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases: click here.
22. Intestinal Inflammation Modulates the Epithelial Response to Butyrate in Patients With Inflammatory Bowel Disease: click here.
23. Diet as a Trigger or Therapy for Inflammatory Bowel Diseases: click here.
24. Inflammatory bowel disease: can omega-3 fatty acids really help?: click here.