Slipping through the Cracks: Linking Low Immune Function and Intestinal Bacterial Imbalance to the Etiology of Rheumatoid Arthritis

Table 1

Internal and exogenous factors possibly involved in the pathogenesis of RA and other ADs: two unrelated types of risk factors apparently contribute to the development of ADs: the first is environmental exogenous factors, and the second is the host’s physical condition. In addition, ADs such as RA might be classified into two types, autoantibody-mediated and non-antibody-mediated. Regardless of whether the disease is mediated by autoantibodies or not, bacterial toxins absorbed from the intestine directly trigger and exacerbate an inflammatory reaction.

Types of risk factors	Antibody-mediated; arthritis	Non-antibody-mediated; arthritis
Exogenous factors	Possible risk agents
Mimic antigens	Dietary collagen [29, 30],; Cartilage PG [94]	/
Pathogenic and nonpathogenic; bacteria	PAMPs [13, 14, 95]	PAMPs [13, 14, 95]; Arthritogenic PG-PS [96]
Bacterial toxins	LPS [28, 97],; MAM [28, 98], and SEB [99]	LPS [30], SEB [3]
Foods and drugs	High fat diet [90],; Proteinase inhibitor, and NSAID [30]	High fat diet [90],; Proteinase inhibitor, and NSAID [30]
Host’s physical condition	Possible risk events
Immune function	Immunosenescence [47, 49]; GI disorders [44]	Immunosenescence [47, 49]; GI disorders [44]
Mucosal barrier function	Stress [41, 42, 100]; GI disorders [44]	Stress [41, 42, 100]; GI disorders [44]
Intestinal bacterial balance	Bacterial imbalance [16, 18, 75]; High toxin level in GI tract	Bacterial imbalance [16, 18, 75]; High toxin level in GI tract