Slide source biomeonboardawareness.com

Microbiome DIET Mechanisms Prevent or Manage Disease (Focus: SCD & IBD)

Summary: Watch the short video to learn why most of your immunity resides in your gut. Then read about predictive autoimmunity in preventative medicine; the role of gut permeability, and disease, as well as how autoimmunity may contribute to cardiovascular disease risk, and the role of antibodies in unexplained miscarriages. The pearl is have a healthy gut which is your first-line immune defense. To that end, learn what the microbiome diet mechanisms are that prevent or manage disease with a focus on SCD and IBD.

The only way to understand diet modulation of microbiome is to first go down the rabbit hole of your gut and see for yourself the complexity that is driven by the food you feed and fuel your microbiome. The below video animation takes you there unveiling the complexity of mucosa immunology in health and disease.  You’ll come out appreciating the role of your gut and mucosa, which is the largest and most dynamic immunological environment within your body for it is the mucosa that hosts the body’s largest population of immune cells.

While indeed complex, the key cells and molecular players involved in gut immunohomeostasis and disease are:  crypts, Tcells, dendritic cells (regulators of innate and adaptive immunity by acquiring, processing, and presenting antigens to T cells), antigens, tolerogenic activation (tolerogenic cells induce regulatory Tcells), anti-inflammatory response, Tregs (specialized T cells that exert immunosuppressive function), IL-10, tumor necrosis factor, neutrophils…  

Now that you appreciate the complexity of the digesting gut, you can understand  why I find it beneficial to better understand SCD, which is a gut healing protocol, so that you can decide what parameters you may want to implement to prevent or manage chronic disease.  This post answers the question, What mechanisms  of diet heal a gut and foster a healthy microbiome?” 

To see a gut gone bad, roll over the below schematics.  In every human, gluten causes the tight junctions to open by stimulating zonulin, according to Dr. Alessio Fassano, MD).  The slides by Aristo Vojdani, PhD, MSc, MT, CEO and technical director of Immunosciences Lab., and Chief Scientific Advisor at Cyrex Laboratories show ramifications of a leaky gut.  Cyrex’s fame is autoimmune antibody detection often resulting from a leaky gut.  For example, detection of such, especially in the years preceding disease diagnosis, enables a window of opportunity where diet and lifestyle modifications may be able to stave off disease occurrence.  

And in this video, Professor Yehuda Shoenfeld, MD, FRCP,  another forefront researcher defining autoimmunity and the role of predictive autoimmunity in preventative medicine, explains the connection between gluten, gut permeability, and disease, as well as how autoimmunity may contribute to cardiovascular disease risk, and the role of antibodies in unexplained miscarriages; the pearl is have a healthy gut which is your first-line immune defense.

DrShoenfeld
http://theglutensummit.com/prof-yehuda-shoenfeld-md-frcp/

Microbiome Diet:  Now, the mechanism of dietary impact on gut microbiome health with a focus on IBD, although all applies to all chronic disease.

The Specific Carbohydrate Diet [SCD] manages and induces remission for many diseases as it is a healing gut protocol.  For background, SCD was originally developed for treating celiac disease by a New York pediatrician, Dr. Sidney Haas, in the 1920s. It remained the guiding therapy until the1950s, when Dr. Dicke published his thesis that wheat flour really was the culprit behind celiac based on his observation that post WWII, celiac disease dramatically returned since wheat replaced potato starch.  SCD continues to be used by many for it’s gut healing abilities.

Dr. Ece Mutlu, RUSH University Medical Center, investigates SCD and other dietary interventions for IBD (see the below abstract or see here and here),  but there are others as well.  See John’s Hopkins here,  Seattle Children’s Hospital here,  Stanford University here, and University of Pennsylvania here just to name a few other investigators. 

Mutlu, SCD and IBD_Abstract 2012
Slide source: biomeonboardawareness.com

In the paper To Diet or Not If You Have Inflammatory Bowel Disease,” 2008, also here and at pubMedDr. Ece Mutu, MD and Niraj Gor, MD present mechanisms behind dietary treatment for the management of IBD looking at: the immune function, antigen load, gut microbiota, gut barrier function, xenobiotic load, and healing of the gut mucosa.

Dietary Therapy Can Alter Immune Function Directly

Dietary therapy can alter immune function directly; for example, vitamin A and retinoids in the diet are essential cofactors for T-cell differentiation into tolerance-inducing T-regulatory cells and away from proinflammatory Th-17 cells [8–11].

Vitamin D deficiency exacerbates experimental colitis in well-established models of IBD [12–15].

Many IBD patients are deficient in vitamins and trace elements, and it is thought that replacement of these may help with immune tolerance.

Dietary exposure to aluminum (a cofactor for immune stimulation required in many vaccines) from food grown in aluminum-rich soil at industrial sites, or in the form of leavening products or additives in processed cake mixes, cheeses, cream powders or frozen dough, preservatives, food coloring, from cookware, or in cola drinks can potentially increase inflammation, at the very least in animal models of IBD [16].

Consistent intake of omega-3 fatty acid or arachidonic acid-rich foods may potentially help decrease immune activation through alterations in prostaglandins and leukotrienes, as well as PPARs [17,18].

Spices such as turmeric can directly alter NFκB, a critical nuclear factor that affects numerous inflammatory signals.  In particular,   NFκB controls the expression of genes encoding the pro-inflammatory cytokines, chemokines, adhesion molecules, inducible enzymes (COX-2 and iNOS), growth factors, some of the acute phase proteins, and immune receptors, all of which play critical roles in controlling most inflammatory processes .  As such, much attention has been spent this past decade trying to identify the compounds responsible for the possible inhibitors of the NF-kappaB pathway as it is an attractive therapeutic target for drugs to treat many inflammatory diseases, including arthritis, asthma, and the auto-immune diseases.  Other biologically active substances that alter NF-κB include dietary lignans found in flax and brans, as well as quercetin found in citrus fruits, red onions, capers, apples, cherries and a number of berries and green leafy vegetables [19].

Diet Can Alter Dietary Antigen Load

Heavily processed foods are a staple of the urban Western world where IBD runs rampant. Limiting such foods may decrease exposure to complex antigens, expected to be found in processed foods, which tend to contain numerous ingredients and nutritionally empty additives and preservatives.

The typical urban grocery store has produce and foods that are not locally grown but are flown in from multiple countries far away. Such foreign dietary antigens may pose new challenges to an individual’s immune system, which may not have evolved to tolerate them. As such, locally grown organic produce may help some subjects.

A diet that is low in typical food allergens, such as wheat, soy and corn, may also be beneficial in some subjects with IBD.

 Diet can alter Gut Microbiota

Low doses of antimicrobials and fungicides and other naturally derived or synthetic pesticides are found in everyday food items, from grated cheese to fruits such as clementines. Some of these alter both structure and function of aquatic microcommunities, and others have in vitro activity against human microorganisms. The effects of these on gut microbiota have not been studied but it is only logical to postulate that they may be important, especially in genetically susceptible hosts.

Exposure to probiotic foods that promote the growth of ‘good’ microbes, which attenuate the immune response, may be beneficial to IBD patients. Examples of such foods include artichokes and chicory, which have large amounts of inulin and oligofructose [20].  [I am adding note:  SCD yogurt and fermented vegetables is a staple of SCD and GAPS.  This post provides technical details for the SCD yogurt including comparison of it’s vastly richer probiotics compared to that commercially available.)

Some studies report that IBD flare-ups are preceded by large intakes of processed sugars. Such carbohydrates and fiber, which are the primary source of nutrients for bacteria, may also affect the composition or function of the colonic microbiota [21,22].

In addition, a vitamin A-deficient diet can increase total bacterial load [23].

 Diet Can Alter Gut Barrier Function

In susceptible individuals, substances such as carrageenan or emulsifiers as part of food, or emulsifiers and detergents as contaminants, can erode the mucoid layer, a major component of gut barrier function. In fact, carrageenan, used as a thickening agent in numerous products such as soy milk and ice cream, induces colitis in animal models of IBD [24].

A diet rich in antioxidants on the other hand can help strengthen tight junctions, which break down under oxidative stress, a major source of which is neutrophilic burst. Examples of high-potency antioxidant substances in food include resveratrol from red grapes and wine, or polyphenols found in green tea.

Colonic bacteria are known to modulate gut barrier function [25]: a dietary change especially in fiber and carbohydrates could affect the colonic microbiota’s ability to produce protective short-chain fatty acids (which are the primary fuel for colonocytes) or toxic volatile substances (which can harm the intestinal barrier) [26,27].

 Diet Can Affect Xenobiotic Load

Chemically active substances that cross into the epithelial layers are usually excreted out of the cells by mucosal transporters such as the p-glycoprotein. In animals, MDR gene-knockouts develop spontaneous colitis, and several human studies point towards the role of MDR gene polymorphisms in IBD [28]. Function of p-glycoprotein can be significantly affected by curcumin in turmeric, ginsenosides in ginseng, piperine and catechins in green tea [29].

 Diet can Promote Healing of the Gut Mucosa

Zinc is well known to decrease diarrhea and promote wound healing. It is an essential trace element and frequently observed to be deficient in IBD patients.

Lastly, SCD alters the gut microbiome
  1. Dr. Ece Mutlu presented this RUSH University Medical Center, Chicago study showing SCD dieters had greater intestinal bacterial diversity addition to having a differing microbiome composition compared to controls.  “I have observed that a small number of my own IBD patients drastically improved on the SCD and achieved complete long-term mucosal healing, or were able to reduce or discontinue immunosuppressants for several years.”  This study showed that whole foods and eliminating certain carbohydrates is managing IBD by modulating and optimizing the gut microbiome.
  2. This June, 2014 study: OBJECTIVE:: To prospectively evaluate clinical and mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn’s disease (CD).  RESULTS:: Clinical and mucosal improvements were seen in children with Crohn’s using the SCD over 12 and 52 weeks.  Additionally, capsule endoscopy can monitor mucosal improvement in treatment trials for pediatric CD.  Further studies are critically needed to understand the mechanisms underlying SCD’s effectiveness in children with CD.   16 IBD children, who were monitored on SCD for 12 weeks:  Harvey Bradshaw significantly decreased from 3.3 + 2.0 to 0.6 + 1.3 (p = 0.007) as did Pediatric Crohn’s Disease Activity Index (21.1 + 5.9 to 7.8 + 7.1; p = 0.011). Lewis Score declined significantly from 2153 + 732 to 960 + 433 (p = 0.012).   Seven patients continued the SCD to 52 weeks with HB (0.1 + 0.4) and PCDAI (5.4 + 5.5) remaining improved (p = 0.016 and 0.027 compared to baseline) with mean LS at 1046 + 372 and 2 patients showing sustained mucosal healing. The study admission criteria required diagnosis of active Crohn’s with PCDAI ≥ 15.
  3. This UMass study showed success for 24 IBD patients eating a whole foods diet which follows the guidelines of a slightly modified SCD diet.  Conclusion:  “The SCD modified dietary protocol can be used as an adjunctive or alternative therapy for the treatment of IBD. Notably, 9 out of 11 patients were able to be managed without anti-TNF therapy, and 100% of the patients had their symptoms reduced.
  4. This Stanford SCD clinical trial induces IBD remission in an estimated 120 adult or pediatric  Crohn’s patients and then evaluates if SCD can be used to retain remission (effective 4/12 thru 7/15).
  5. This Department of Pediatrics, Seattle Children’s Hospital and University of Washington, Seattle, WA paper documents 7 children with Crohn’s Disease receiving SCD and no immunosuppressive medications: all symptoms were notably resolved at a routine clinic visit 3 months after initiating the diet.  Laboratory indices included: albumin, C-reactive protein, hematocrit, and stool calprotectin, either normalized or significantly, improved during follow-up clinic visits. –  This studies name is: “Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet,” [J Pediatr Gastroenterol Nutr. 2014] – PubMed.
  6. John’s Hopkins and Maryland University AND  CCFA are now beginning to incorporate SCD/PALEO requirements within the framework of IBD management.  Check out their PowerPoint presentations: Johns Hopkins “Nutrition Tips For IBD,” dated March 2013 and CCFA “Food For Thought,” dated April 2013.  This slide from the Johns Hopkins presentation depicts the 4 popular IBD diets and notes lack of evidence, however this is mainly due to lack of completed studies, although such is now ongoing:
Johns Hopkins Nutrition Tips For IBD slide_diet study summaries
Slide source: Johns Hopkins Medicine “Nurition Tips for IBD,” http://www.hopkinsmedicine.org/IBDsymposium/Presentations_2013/Mullin_Lipski_Nutrition_Final.pdf

7.  The Johnson Center for Child Health & Development: Research ongoing evaluations:  SCD in 20 children ages 2-6 years with gastrointestinal problems that have been diagnosed with autism.  Enrollment is now closed;  they will eat a SCD diet for 16 weeks (all food is provided) and blood, stool, and questionnaires will be obtained.  The contact for moreinformation on this study is  intake@johnson-center or call 512.732.8400.

Probiotics and Butyrate

Last, I would be remiss to not mention the role of probiotcs and compounds produced by microbiome that modulate immunity.   This post discusses some of the SCD probiotic information.  And this Journal of Medical Microbiology paper discusses much technicals regarding butyrate, which is a by-product of certain microbiome bacterial species through fermentation of dietary fibre, or there may be an increase in butyrate production resulting from a direct stimulation of butyrate producers or indirect effects such as metabolic cross-feeding of fermentation products from other bacterial groups (Flintet al., 2007).  The benefits of butyric acid: first, it is the preferred source of energy for colonocytes. It affects cellular proliferation, differentiation and apoptosis. Moreover, butyric acid has well documented anti-inflammatory effects. Inhibition of histone deacetylase activity, resulting in hyperacetylation of histones, and as a consequence suppression of nuclear factor-kappa B activation, is a likely explanation. Secondly, it has been proposed that butyric acid reinforces the colonic defence barrier by increasing production of mucins and antimicrobial peptides. Thirdly, it has been shown that butyric acid decreases intestinal epithelial permeability by increasing the expression of tight junction proteins. Anti-inflammatory activities, combined with a strengthening of the mucosal barrier integrity, are ideal properties for therapeutic compounds against IBD-like syndromes. Indeed it has been shown that butyrate enemas can yield positive results in the treatment of active UC (Breuer et al., 1997). 

IBD are known to have reduced butyrate.  Resistant starch, termed the third starch, increases butyrate.  The Journal of Medical Microbiology paper noted, “An ideal probiotic would thus be a colonizing bacterium that combines systemic anti-inflammatory and immunoregulatory effects with delivery of high butyrate levels at the site of action and that can be ingested in a stable form, such as spores [I assume to survive the digestive tract and ph conditions therein].”

 What should an IBD Patient eat?

There are no good answers to this question, as there are little to no scientific data in this regard. There is no diet that has been proven to work in IBD.

In summary, dietary therapy has the potential to be a strong addition to the clinical armamentarium against IBD. Subjects who plan on going on diets should be encouraged to consult their treating physicians and enroll in clinical trials of dietary treatment. Physicians and scientists alike need to invest further time and effort into studying diet as a therapy or an environmental factor in IBD. It is only with such involvement that answers can be generated to what the IBD patient should eat.

 Precautions

While it seems logical to think that diet can have a significant impact in IBD, dietary restrictions can also be costly for a symptomatic IBD patient who may already be losing weight and malnourished. Restricted diets are often poor in micronutrients and trace elements, the depletion of which can sometimes have irreversible consequences. Food is a big part of social life – almost every social gathering from holidays, sports events or a simple picnic over a weekend, to class reunions, visits with friends and family, business meetings and art galas, all revolve around food. Therefore, restrictive diets may have a further negative impact on the life of an IBD patient, who may already have social restrictions from symptoms.

 Website

Mutlu E. Dietary treatment of Crohn’s disease. (2005) www.clinicaltrials.gov/ct2/show/NCT00343642
Read More: To diet or not if you have inflammatory bowel disease, Expert Review of Gastroenterology & Hepatology, Informa Healthcare   http://informahealthcare.com/doi/full/10.1586/17474124.2.5.613
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Last updated: February 18, 2017 at 9:04 am

In health and awareness,

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