Figure 9.

Model for microbiota involvement and monocyte turnover in RA. This model illustrates the turnover of monocytes in active RA compared to healthy and RA during fasting with microbiota reduction. Dysbiotic gut microbiota induces inflammation, leaky gut and spreading of microbial components into the body with affinity to joint tissue structures, especially components of the extracellular matrix. Monocytes become involved with accumulation and activation in the gut and inflamed tissue sites. Increased monocyte involvement induces increased production in the bone marrow and increased migration from the blood circulation into the inflamed tissues. Shorter circulation time reduces maturation in the blood from classical (released from bone marrow) to non-classical monocytes, which represent the phenotype with reduced capacity for activation by lipopolysaccharides (decreased CD14 expression) or migration into tissue (decreased L-selectin expression) but increased capacity for clearing of immune complexes (elevated CD16 = FcγRIII expression). Microbiota reduction and fasting in RA reduces microbial triggers and thus monocyte turnover, joint inflammation, and levels of IL-6 and zonulin. IL-6: interleukin 6; TNF: tumor necrosis factor.