The gut microbiota in humans is very active providing the release of a variety of metabolites with profound effects on human health and immune regulation. These metabolites and compounds derived from the microbiota exert inflammatory and anti-inflammatory effects in the intestinal tissues and systemically.
Microbial species maintain immune system balance in multiple ways. An individual’s genetic profile (HLA profile) shapes the microbial populations in the intestine. This was first discovered with HLAB27 positive patients with axial spondylitis.
There is a condition called ” leaky gut”, resulting from damage to the epithelial cells lining the intestine, which permits entry of bacteria and pro-inflammatory metabolites along with other products into the intestinal lumen and into the bloodstream. This can cause both local and systemic inflammation. In this condition bacteria and chemical byproducts can leak into the bowel resulting in the activation of intestinal T cells. These T cells can migrate to several sites including the brain, joints and the ends of ligaments( entheses).
There are many research studies that are driving and increasing interest in ways of reversing leaky gut conditions and preventing immune activation. There is one recent study demonstrating the inhibition of leaky gut with the short chain fatty acid, butyrate. This is a mice study but has implications for humans.
Recent studies have shown that in individuals with less diversity of microbial species in the bowel and lower levels of medium chain fatty acids can be found in patients with psoriatic arthritis. Studies are now increasing the concept of a gut-joint axis.
The composition of our dietary intake is a major factor modulating the structure of the microbiome.
The Modern Diet.
Modern diets are rich in carbohydrates, salt and saturated fatty acids and deficient in fiber, vitamins and minerals. The western diet is associated with unprecedented rates of obesity. There is a spike in chronic inflammatory diseases and autoimmune conditions. The hypothesis is that this may be related. In obesity there is a change to the inflammatory molecules and to the intestinal microbiome. The fact that obesity is a major risk factor for psoriasis and PsA and that these patients suffer from higher rates of metabolic syndrome, type 2 diabetes and cardiovascular disease has prompted efforts to understand if weight loss or efforts to alter the microbiome can lessen inflammation in these disorders. This strategy is bolstered by the fact that negative energy balance, achieved by expending more energy than consumed, drives integrated immunometabolic responses that promote longevity and counter-balance inflammatory pathways.
Several studies in RA over the past 30 years demonstrate that hypocaloric and anti-inflammatory diets can lessen inflammation.
In a recent presentation at the American Academy of Allery, Asthma and Immunology, Dr. Guma from UCSD, showed that RA patients treated for 2 weeks with an anti-inflammatory diet demonstrated significantly improved clinical outcomes (Joint swellin, pain, fatigue) without significant weight loss compared to the control group. Moreover, responders had a significant change in the microbiome in terms of composition and diversity. These dramatic changes over a 2 week period demonstrate the powerful effects of dietary intervention on chronic inflammation.
In another study in psoriatic arthritis a 14 week aggressive hypocaloric diet resulted in dramatic weight loss and these patients showed significant improvements in multiple clinical features and inflammatory parameters of arthritis that were maintained on follow-up a year later. Other case series finds that bariatric surgery in psoriasis patients is associated with marked improvements in psoriasis.
These studies are changing the paradigms of treatment and that along with standard anti-inflammatory therapies, a focus on nutrition improves outcomes.