Gut-joint connection promising in psoriatic arthritis

Mounting circumstantial evidence points to perturbation of bacterial communities in the gut and skin as important environmental triggers for psoriasis and psoriatic arthritis.

A distinctive pattern of alterations in the skin micro biota, termed bacterial “cutaneotypes,” has recently been documented in lesion and uninvolved skin of psoriasis patients. Similarly, psoriatic arthritis patients show decreased diversity of their intestinal bacterial community in a pattern similar to patients with inflammatory bowel disease, said at the Winger Rheumatology Symposium sponsored by the American College of Rheumatology.

The current working hypothesis of disease pathogenesis is that, in individuals genetically predisposed to psoriasis or psoriatic, this microbial dysbiosis at the cutaneous and gut levels provides an environmental trigger for overt expression of clinical disease.

“This dybiosis is potentially relevant as a diagnostic and /or therapeutic target in psoriasis and psoriatic arthritis. For example, it may eventually become possible to assess the gut micro biota to predict which psoriasis patients will later develop psoriatic arthritis. And reconstituting the gut flora may turn out to have therapeutic benefit. But much more work is needed,” explained by the director of the Microbiome Center for Rheumatology and Autoimmunity at New York University.

About 25-30 percent of psoriasis patients develop inflammatory psoriatic arthritis, most often roughly seven years after onset of their skin disease. Genetics clearly plays a role, as shown in a classic Danish twin registry study with more than 21,000 subjects. Fifty- five percent of the siblings of monozygotic twins with psoriatic arthritis had skin psoriasis, but only 10 percent of the siblings had psoriatic arthritis, as did 3.8 percent of siblings of dizygotic twins with psoriatic arthritis. The lesser concordance rate seen for psoriatic arthritis hinted at the importance of environmental factors in disease genesis.

Subclinical gut inflammation is common in psoriatic arthritis. In one early study, histologic evidence of mild or moderate gut mucosal inflammation was detected in 45 percent of a group of psoriatic arthritis patient, compared with 15 percent of patients with rheumatoid arthritis and 0 percent of controls.

Also, psoriasis patients are at a roughly3.5-fold increased risk of developing Crohn’s disease. Among patients with established psoriatic arthritis, this risk climbs to 6.5- fold greater than in nonpsoriatic controls.

In a soon- to-be- published study, they have taken the field a step further, employing high-throughput gene sequencing to analyze the gut bacterial communities of psoriatic arthritis patients and controls. These were all new-onset psoriatic arthritis patients who had never been exposed to systematic corticosteroids, biologic agents, or conventional disease-modifying anti-rheumatic drugs.

Compared with the stool samples of healthy controls, several major bacterial species were underrepresented of absent in the gut micro biota of psoriatic arthritis patients. These include Akkermansia, the most common mucolytic bacterium in healthy subjects. Intriguingly, Akkermansia counts are decreased 15- fold in Crohn’s disease and 92-fold in ulcerative colitis.

Other bacterial species markedly less abundant in the psoriatic arthritis patients ‘gut flora were Ruminoccocus Alistipes and Roseburia. Like Akkermansia, these are mucin-degrading bacteria that promote a healthy gut environment, and they, too, are reduced in inflammatory bowel disease.

Theorize that these disruptions of the bacteria ecosystem might arise from a course of antibiotics, a change in diet, or other insults. The result is activation of dendritic cells to produce jnterleukin-23, which triggers a pro inflammatory cascade including tumor necrosis factor -alpha, interleukin -22, and antimicrobial peptides.

As shown by other investigators these pro inflammatory cytokines inhibit RANK ligand, which is the critical factor for differentiation of microfold cells in the gut. These micro fold cells, or M cells, are specialized epithelial cells that transport antigens across the gut epithelium and play an important role in maintenance of an efficient response. It’s plausible that, when these M cells are defective, the resultant loss of tolerance and chronic inflammatory can result in psoriatic arthritis.

At New York University have used high-throughput gene sequencing to analyze the cutaneous micro biota of lesional and nonlesional skin in psoriasis patients, as well as ski samples from the same sites in healthy controls. The impetus for the study was a hypothesis that psoriasis might represent an inappropriate cutenous immune response directed against offending bacteria in the skin micro biota.

Sure enough, the bacterial community present in psoriatic lesions displayed a markedly decreased diversity, compared with controls.

This decreased diversity also was present, albeit to lesser extent, in the psoriasis patients’ nonlesional skin. Both the lesional and nonlesional skin of psoriasis contained an increased abundance of Corynebacterium, Staphylococcus, and Streptococus, compared with controls.

In addition, the skin micro biota could be classified into one of two characteristic patterns, which the investigators termed “cutaneotypes.” Cutaneotype 1, which predominated in the skin of normal controls, contained an abundance of Proteobaceria. In contrast, cutaneotype 2, which was 3.5-fold more prevalent in psoriatic lesion than in controls, was enriched in Firmicutes and Actinobacteria. The psoriatic patients’ nonlesional skin contained a balance of cutaneotypes 1 and 2.

It is said that the next step in research is to learn whether the gut micro biota of psoriasis patients differs from that of psoriatic arthritis patients.

The following patients with psoriasis; and for those who later convert to psoriatic arthritis, want to know if there’s alteration of their bacterial immunity, both in the gut and the skin.