sure thing, i'll go and add in some references. that was the forum post version aimed at an audience of AS patients. i do plan to do an academic write up at some stage but it would be a lot more detailed as that was just a brief overview of each mechanism. however when i do go back to write it up it would help if what i had done so far was already referenced so i will go back and add them in and repost below with references included.

* version 2.0 with references added and some minor edits and additions.
Van Nostrand Academy of Experimental Applied Rheumatology, Hoffer Mandoff Neo-Clinic, Belgium.
Feel free to print, share or do whatever you like.

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 (1, 2). What is less well known is the potential of therapeutic diets to treat specific pre-existing diseases. Different diseases have different potential to be influenced by diet as diseases lie on different parts of the spectrum ranging from strongly genetic diseases such as Sickle-cell disease (3), to strongly environmental such as obesity (4). 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 (5, 6). 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 (7). 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 (8, 9).

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 (10). AS shares some of the same genetic risk factors as IBD (11, 12). The majority of AS patients also have increased intestinal permeability as well as ulcerated lesions in the gut (most commonly in the terminal ileum) which resemble chronic ileocolitis and are often indistinguishable from Crohn's disease (13, 14, 15, 16). The strong relationship between gut and joint inflammation was confirmed in one study which found that remission of joint inflammation was always connected with a disappearance of gut inflammation (17). AS definitely fits the profile of a disease that has the potential to be influenced by diet as it is a disease in which environmental factors have been found to be important and also a disease in which the gut and inflammation play 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 and gut inflammation are more likely to have food allergies (18, 19, 20). 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 (21). 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 (22). In a trial of dairy elimination in SpA patients, 17/24 patients reported improvements, 8 were able to discontinue NSAIDs and in a two year follow up 6 no longer required any drug therapy (23). Food allergies can be detected by IgE antibody testing. The value of IgG testing is currently controversial.

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 (24). Feeding carrageenan to rats causes ulcerative colitis (25), in humans it triggers gut inflammation through various inflammatory pathways and may interact with genes that predipose to Crohn's disease (24, 26, 27).

Proinflammatory and anti-inflammatory compounds - Foods contain compounds which can can promote inflammation and trigger inflammatory pathways and also compounds which can reduce inflammation through pathways such as NFkappaB and Cox-2 (28, 29). Some examples of proinflammatory compounds are trans fats (hydrogenated vegetable oil) and arachidonic acid (animal fats) (28). Some examples of anti-inflammatory compounds are - quercitin (apples), catechins (green tea), circumin (turmeric) and hesperidin (citrus fruits) (30). 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 (31).

Bacterial species composition - Everybody has a unique gut microbiome. A study on AS patients found a unique and stable bacterial community in each individual (32). Different species of bacteria stimulate different proinflammatory and anti-inflammatory immune pathways to different degrees (33, 37). 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 (34, 35). 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 (34, 35). Polysaccharides such as inulin and FOS (often referred to as prebiotics) can influence species composition (36).

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 (37). 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 which increases the risk of developing IBD (37). 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 (38).

Gut bacteria metabolites - Diet composition influences the metabolites that are produced by bacteria (39). Different food compounds are broken down by bacteria into various byproducts such as butyrate, acetate and hydrogen sulfide (39). Some of these metabolites such as butyrate (from fibre and resistant starch) have beneficial anti-inflammatory effects whears others such as hydrogen sulfide (from animal protein) can contribute to gut inflammation (39).

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 (40). Vitamin A can help reduce Th17 cells (41). Magnesium deficiency can cause an increase in inflammatory cytokines (42) whilst higher magnesium intake is associated with lower inflammatory markers (43, 44). Higher vitamin B6 intake is associated with lower CRP levels (45) and supplementing vitamin B6 reduced Il-6 and TNF-a in RA patients (46). Vitamin k2 can help prevent soft tissue calcification (47).

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 (48). Obesity also predisposes to increased Th17 levels which have been associated with more pronouned autoimmune disease (49). Two studies have found increased prevalence of metabolic syndrome in AS patients compared the general population (50, 51).

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 without caloric restriction (52). Alternate day calorie restriction resulted in decreased TNF-a levels in asthma patients (53). A recent rat study found that reduced eating frequency prevented metabolic syndrome and reduced inflammatory markers independent of caloric intake (54). Intermittent fasting has been found to reduce levels of Il-6 and CRP (28).

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.

References

1) 'Diet, obesity and cancer' - http://www.ncbi.nlm.nih.gov/pubmed/21174166
2) 'A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart Disease' - http://archinte.jamanetwork.com/article.aspx?articleid=1108492
3) 'Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study' - http://onlinelibrary.wiley.com/doi/10.1002/ajh.21572/abstract
4) 'Human Obesity: A Heritable Neurobehavioral Disorder That Is Highly Sensitive to Environmental Conditions' - http://diabetes.diabetesjournals.org/content/57/11/2905.full
5) 'Gene–environment-wide association studies: emerging approaches' - http://www.nature.com/nrg/journal/v11/n4/abs/nrg2764.html
6) 'Genetic and environmental pathways to complex diseases' - http://www.biomedcentral.com/1752-0509/3/46/
7) 'The genetic background of ankylosing spondylitis' - http://www.ncbi.nlm.nih.gov/pubmed/19541528
8) 'Current Guidelines for the Drug Treatment of Ankylosing Spondylitis' - http://www.ingentaconnect.com/content/adis/dgs/1998/00000056/00000002/art00006
9) 'Frequency and characteristics of disease flares in ankylosing spondylitis' - http://rheumatology.oxfordjournals.org/content/49/5/929.full
10) 'The gut microbiota shapes intestinal immune responses during health and disease' - http://www.nature.com/nri/journal/v9/n5/abs/nri2515.html
11) 'The Immune Response to Gut Bacteria in Spondyloarthritis: A Role in Pathogenesis' - http://www.slm-rheumatology.com/the-jour...pathogenesis-2/
12) 'A common genetic background for inflammatory bowel disease and ankylosing spondylitis: a genealogic study in Iceland' - http://www.ncbi.nlm.nih.gov/pubmed/17665420
13) 'Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives' - http://rheumatology.oxfordjournals.org/content/33/7/644.short
14) 'Alterations in intestinal permeability' - http://www.ncbi.nlm.nih.gov/pubmed/16966705
15) 'Ileocolonoscopic Findings in Seronegative Spondylarthropathies' - http://rheumatology.oxfordjournals.org/content/XXVII/suppl_2/95.short
16) 'Gut inflammation and spondyloarthropathies' - http://www.ncbi.nlm.nih.gov/pubmed/12427369
17) 'Course of gut inflammation in spondylarthropathies and therapeutic consequences' - http://www.sciencedirect.com/science/article/pii/S0950357996800100
18) 'Gut mucosal response to food antigens in Crohn's disease' - http://www.ncbi.nlm.nih.gov/pubmed/12390099
19) 'Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898551/
20) 'Relationship between intestinal permeability and antibodies against food antigens in IgA nephropathy' - http://www.ncbi.nlm.nih.gov/pubmed/8721870
21) 'The effect of dietary yeast on the activity of stable chronic Crohn's disease' - http://www.ncbi.nlm.nih.gov/pubmed/1502481
22) 'Modulation of immune function by dietary lectins in rheumatoid arthritis' - http://cambridgefluids.com/action/displa...d=02&next=Y
23) 'Effect of milk product deprivation on spondyloarthropathy' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1005380/
24) 'Current Availability and Consumption of Carrageenan-Containing Foods' - http://www.ingentaconnect.com/content/routledg/gefn/2003/00000042/00000006/art00001
25) 'Review of Harmful Gastrointestinal Effects of Carrageenan in Animal Experiments' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242073/
26) 'Toll-like Receptor 4 Mediates Induction of the Bcl10-NFkappaB-Interleukin-8 Inflammatory Pathway by
Carrageenan in Human Intestinal Epithelial Cells' - http://www.ncbi.nlm.nih.gov/pubmed/18252714
27) 'Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells' - http://ajpgi.physiology.org/content/292/3/G829.short
28) 'Stress, Food, and Inflammation: Psychoneuroimmunology and Nutrition at the Cutting Edge' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868080/
29) 'NF-kappa B and Nrf2 as potential chemopreventive targets of some anti-inflammatory and antioxidative phytonutrients with anti-inflammatory and antioxidative activities' - http://www.ncbi.nlm.nih.gov/pubmed/18296353
30) 'Chemoprotective Mechanism of the Natural Compounds, Epigallocatechin- 3-O-Gallate, Quercetin and Curcumin Against Cancer and Cardiovascular Diseases' - http://www.ingentaconnect.com/content/ben/cmc/2009/00000016/00000012/art00002
31) 'Bioactive phytonutrients (omega fatty acids, tocopherols, polyphenols), in vitro inhibition of nitric oxide production and free radical scavenging activity of non-cultivated Mediterranean vegetables' - http://www.sciencedirect.com/science/article/pii/S0308814611007886
32) 'Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis' - http://rheumatology.oxfordjournals.org/content/41/12/1395
33) 'Microbes in Gastrointestinal Health and Disease' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892787/
34) 'The Guts of Dietary Habits' - http://www.sciencemag.org/content/334/6052/45.summary
35) 'Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes' - http://www.sciencemag.org/content/334/6052/105.short
36) 'Using probiotics and prebiotics to improve gut health' - http://www.sciencedirect.com/science/article/pii/S1359644603027466
37) 'Host immune response to antibiotic perturbation of the microbiota' - http://www.ncbi.nlm.nih.gov/pubmed/20016473
38) 'Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects' - http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=6371220
39) 'Interactions and competition within the microbial community of the human colon: links between diet and health' - http://www.ncbi.nlm.nih.gov/pubmed/17472627
40) 'Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes' - http://gut.bmj.com/content/56/2/168.abstract
41) 'Regulation of FoxP3+ Regulatory T Cells and Th17 Cells by Retinoids' - http://www.hindawi.com/journals/cdi/2008/416910/
42) 'Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin' - http://www.springerlink.com/content/481162444r825777/
43) 'Magnesium supplement intake and C-reactive protein levels in adults' - http://www.sciencedirect.com/science/article/pii/S0271531706000923
44) 'Dietary Magnesium and C-reactive Protein Levels' - http://www.jacn.org/content/24/3/166.short
45) 'Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status' - http://www.ncbi.nlm.nih.gov/pubmed/19906811
46) 'Vitamin B6 supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis' - http://www.nature.com/ejcn/journal/v64/n9/full/ejcn2010107a.html
47) 'Role of K vitamins in the regulation of tissue calcification' - http://www.springerlink.com/content/g0vnjqgpg1t6cp1m/
48) 'The Inflammatory Syndrome: The Role of Adipose Tissue Cytokines in Metabolic Disorders Linked to Obesity' - http://jasn.asnjournals.org/content/15/11/2792.full
49) 'Obesity predisposes to Th17 bias' - http://www.ncbi.nlm.nih.gov/pubmed/19662632
50) 'High prevalence of metabolic syndrome in patients with ankylosing spondylitis' - http://www.springerlink.com/content/k2107305450v8720/
51) 'High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFalpha treatment: correlation with disease activity' - http://ukpmc.ac.uk/abstract/MED/19473571
52) 'Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production' - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058015/
53) 'Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma' - http://www.sciencedirect.com/science/article/pii/S089158490600801X
54) 'Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet' - http://www.cell.com/cell-metabolism/retrieve/pii/S1550413112001891

Wow jroc - thank you very much! The ref links will sure take me awhile to wade through. Love the AS patient audience version!

Very nice job!