* I put this in main forum rather than NSD/diet forum as people who do not do NSD and don't visit the NSD forum may be interested in other ways that diet can influence AS.

Context

It is well known that diet plays an important role in general health and can influence the susceptibility to common diseases such as obesity, cancer and heart disease. What has received less attention is the role of therapeutic diets to treat specific pre-existing diseases. Different diseases have different potential to be influenced by diet. Diseases lie on different parts of the spectrum ranging from strongly genetic diseases such as Sickle-cell disease, to strongly environmental such as obesity. Most diseases lie somewhere in the grey area in the middle where certain genes or combinations of genes can increase susceptibility but only become pathological under certain environmental conditions. AS falls somewhere in the middle as there is a strong genetic predisposition but only around half of monozygotic twins (who share identical genes as well as many environmental factors) both go on to develop AS. The fact that individual patients can also go through periods of high disease activity and periods of remission also indicates that environmental factors are important in affecting disease activity.

Diseases involving the gut are more likely to be able to be influenced by diet due to the direct interactions between food, gut bacteria and the intestinal immune system. AS shares many genetic risk factors with IBD. The majority of AS patients also have increased intestinal permeability as well as ulcerated lesions in the gut - mostly in the terminal ileum. AS fits the profile of a disease that has the potential to be influenced by diet as it is a disease in which environmental factors are important and also a disease in which the gut plays a significant role.

Mechanisms

There are many mechanisms by which diet could influence gut inflammation and AS. Some of these include
- food allergens
- food intolerances
- proinflammatory and anti-inflammatory compounds
- bacterial species composition
- gut bacteria metabolites
- micronutrient levels
- weight loss
- meal frequency

Food allergens - People with increased gut permeability are more likely to have food allergies. This creates a chicken and egg scenario where it unknown whether a specific food caused gut problems in the first place or whether it is only a problem due to the current state of the gut which was caused by other factors. Whichever is the case there is evidence that consuming foods in which the body is producing antibodies against can be detrimental to gut health and immune mediated arthritis. In an experiment with Crohn's disease patients with raised antibodies against bakers yeast, a yeast exclusion group had lower disease activity than the group that took supplementary yeast capsules indicating that intake of food allergens can adversely affect gut health. Case studies have found that RA patients with dairy allergy that eliminated dairy products significantly improved joint symptoms which were then exacerbated on reintroducting dairy along with increased inflammatory markers. Food allergies can be detected by IgE antibody testing. I'm not aware of any evidence supporting the use of IgG testing.

Food intolerances - Food intolerances are different from food allergies in that the immune system is not mounting a response to the food. Food intolerance can result from the absence of specific chemicals, enzymes, or gut bacteria needed to properly digest a food substance such as lactose in milk which is a common food intolerance. Different people can be sensitive to various compounds in foods such as histamines, FODMAPS, salicylates, benzoates, sulphites, nitrates, amines. Carrageenan is a common food thickener that is indigestible and is broken down by gut bacteria. It contains a high amounts of sulphur which are broken down into volatile sulfur compounds in the gut. Feeding carrageenan to rats causes ulcerative colitis, in humans it triggers gut inflammation.

Proinflammatory and anti-inflammatory compounds - Foods contain compounds which can can promote inflammation and trigger inflammatory pathways and also compounds which can reduce inflammation. Some examples of proinflammatory compounds are trans fats (hydrogenated vegetable oil), heterocyclic amines (grilled meat). Some specific anti-inflammatory compounds are - quercitin (apples), catechins (green tea), circumin (turmeric), hesperidin (citrus fruits). Anti-inflammatory food compounds are usually types of phytonutrients such as phenols, polyphenols, flavonoids, isoflavones, terpenoides, and glucosinolates which are commonly found in fruits, vegetables and other plant foods.

Bacterial species composition - Everybody has a unique gut microbiome. A study on AS patients found a unique and stable bacterial community in each individual. Different species of bacteria stimulate different proinflammatory and anti-inflammatory pathways to different degrees. Studies have found that the microbiome can change quickly in response to changes in diet and that long term diet may be a key determinent of the proportion of bacteroides, prevotella, and ruminococcus species. Changes in species composition can occur due to different levels of macronutrients (carbohydrates, protein, fats) and other food compounds that are broken down by bacteria such as fibre, polyphenols and polysaccharides. Polysaccharides such as inulin and FOS (often referred to as prebiotics) can influence species composition.

Total bacteria numbers (biomass) also have an influence on intestinal immunity. Following antibiotic use biomass is drastically reduced which causes less stimulation of the intestinal immune system by bacteria which means less gut inflammation. In the short term this means less inflammation but increases the risk of pathogenic bacteria or yeast overgrowth as the two main protecting factors - competitive exclusion by commensal species and the intestinal immune system are compromised. A study that assessed gut bacteria changes following a gluten free diet which lowered starch intake found that the levels of many 'beneficial' bacteria was reduced whilst the levels of some potentially harmful bacteria increased although the net effect was a decrease in gut inflammation possibly due to decreased biomass.

Gut bacteria metabolites - Diet composition influences the metabolites that are produced by bacteria. Different food compounds are broken down by bacteria into various byproducts such as butyrate, acetate, hydrogen sulfide. Some of these metabolites such as butyrate (from fibre and resistant starch) have beneficial anti-inflammatory effects. Others such as hydrogen sulfide (from animal protein) can contribute to gut inflammation.

Micronutrients - Vitamins and minerals play imporant roles in the immune system, inflammation and gut health. For example zinc has been found to help prevent gut damage, vitamin A can help reduce Th17 cells, magnesium deficiency can cause an increase in inflammatory cytokines whilst higher magnesium intake is associated with lower inflammatory markers, higher vitamin b6 intake is associated with lower CRP levels and supplementing b6 reduced Il-6 and TNF-a in RA patients, vitamin k2 can help prevent soft tissue calcification.

Weight loss - Diet is one of the most important factors in weight gain or weight loss. Obesity is associated with higher levels of circulating inflammatory markers such as TNF-a and Il-6. It is also predisposes to increased Th17 levels which has been associated with more pronouned autoimmune disease. Two studies have found increased prevalence of metabolic syndrome in AS patients compared the general population.

Meal frequency - Some evidence suggests that reduced meal frequency may reduce inflammation. One study found lower TNF-a and Il-17 levels in peripheral blood cells with reduced meal frequency. Alternate day calorie restriction resulted in decreased TNF-a levels in asthma patients. A recent rat study found that reduced eating frequency prevented metabolic syndrome and reduced inflammatory markers indpendent of caloric intake. Intermittent fasting has been found to reduce levels of Il-6 and CRP.

In summary AS is a disease which has the potential for diet to play an important role in disease managment. There are a number of mechanisms by which dietary choices and patterns could influence disease activity which involve many complex and interrelated biological pathways. This raises the question of what types of dietary interventions are more likely to have a positive impact. In Part 2 I'll examine some popular diets aimed at improving gut health and reducing inflammation, look at the evidence supporting them, and how individual genetic differences and other environmental factors can influence the response of different people to different diets.

* In order to save time I haven't included references. If you would like a reference for any particular part just let me know and I'll put up a link.

nice read. waiting for part 2

This is an excellent summary.

Great effort.

jroc - good one. Awaiting part 2.

Do you have a link to the original paper jroc? Would like the whole thing. - if poss.

Thanks.

i haven't had it published yet

Woo-Hoo Jroc - good one. Excellent paper. Many congrats -

Really excellent summary - just the right amount of technical talk there for me to easily understand. Looking forward to part 2 as well

thanks for all the feedback, good to hear that it wasn't too much technical jargon as it's sometimes hard to judge how much to put in and how much to leave out.

Hi jroc,... I think I am going to print this out for my rheumatologist! Would love to have the ref. links to add, if you happen to have them handy and it's not a huge bother to gather them. Send in PM whenever you get around to it and I'll save this to my faves in meantime.

I think you need this --->

Yes - I've saved, and printed out a copy. Joining with mig, re, ref. links. Could you copy me in as well please jroc - again, join mmig, if not too a huge bother to gather. My thanks