AUTHOR=Jeong Yunju , Jhun JooYeon , Lee Seon-Yeong , Na Hyun Sik , Choi JeongWon , Cho Keun-Hyung , Lee Seung Yoon , Lee A Ram , Park Sang-Jun , You Hyun Ju , Kim Ji-Won , Park Myeong Soo , Kwon Bin , Cho Mi-La , Ji Geun Eog , Park Sung-Hwan 

TITLE=Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.736196

DOI=10.3389/fimmu.2021.736196

ISSN=1664-3224

ABSTRACT=<p>The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of <italic>Bifidobacterium</italic> strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of <italic>Bifidobacterium</italic> and <italic>Collinsella</italic> was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of <italic>Clostridium</italic> of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant <italic>Bifidobacterium</italic>, <italic>B. longum</italic> RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of <italic>B. longum</italic> RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, <italic>B. longum</italic> RAPO significantly inhibited Th17 cells and Th17-related genes—<italic>IL-17A</italic>, <italic>IRF4</italic>, <italic>RORC</italic>, <italic>IL-21</italic>, and <italic>IL-23R</italic>—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that <italic>B. longum</italic> RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of <italic>B. longum</italic> RAPO in patients with RA and other autoimmune disorders merit further investigation.</p>