TY - JOUR
T1 - Eggerthella lenta augments preclinical autoantibody production and metabolic shift mimicking senescence in arthritis
AU - Balakrishnan, Baskar
AU - Luckey, David
AU - Wright, Kerry
AU - Davis, John M.
AU - Chen, Jun
AU - Taneja, Veena
N1 - Publisher Copyright:
Copyright © 2023 The Authors.
PY - 2023
Y1 - 2023
N2 - Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta. Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17– and interferon-γ–producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.
AB - Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta. Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17– and interferon-γ–producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.
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U2 - 10.1126/sciadv.adg1129
DO - 10.1126/sciadv.adg1129
M3 - Article
C2 - 37656793
AN - SCOPUS:85169516066
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 35
M1 - eadg1129
ER -