Alteration of the Intestinal Microbiome in the Preclinical Phase of Experimental Arthritis and the Efficacy of Microbiota Modulation in Established Arthritis in Mice

Rebecca Rogier¹, Heather Evans-Marin², Julia Manasson³, Peter M. van der Kraan⁴, Wim B. van den Berg⁵, Marije I. Koenders⁴, Jose U. Scher⁶ and Shahla Abdollahi-Roodsaz^7,8, ¹Experimental Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands, ²Division of Rheumatology, New York University School of Medicine, New York, NY, ³Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, ⁴Experimental Rheumatology, Radboud university medical center, Nijmegen, Netherlands, ⁵Rheumatology Research and Advanced Therapeutics, Radboud University Medical Center, Nijmegen, Netherlands, ⁶New York University School of Medicine, New York, NY, ⁷Department of Medicine, Division of Rheumatoogy, New York University School of Medicine, New York, NY, ⁸Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Animal models, Arthritis, microbiome and mucosal T cells

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Animal Models Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

The composition of intestinal microbiota is perturbed in patients with new-onset and chronic rheumatoid arthritis (RA). However, it is not known whether the changes in the intestinal microbiome precede the development of arthritis or are rather a consequence of the inflammatory processes. Furthermore, while both germ-free condition and administration of oral antibiotics prevent arthritis in mice, it is unclear whether modulation of the intestinal microbiota after the onset of arthritis may still suppress the disease. We aimed to identify alterations of the intestinal microbiome in the preclinical phase of inflammatory arthritis, and evaluate the efficacy of microbiota modulations in the treatment of established arthritis in mice.

Methods:

We sequenced fecal bacterial 16S rRNA genes of mice immunized for the induction of collagen-induced arthritis (CIA) prior to the onset of arthritis compared with naïve condition. To assess the efficacy of microbiota modulation during arthritis, mice with ongoing CIA were treated with oral antibiotics to partially eliminate the intestinal microbiota. T cell differentiation and production of cytokines in intestinal lamina propria and joint-draining lymph nodes were assessed by flow cytometry and Luminex. Arthritis was assessed macroscopically and by histology. K/BxN serum-transfer arthritis was used to assess the role of microbiota in T cell-independent arthritis.

Results:

The preclinical phase of arthritis in mice was characterized by marked changes in the intestinal microbiome, represented by a significant increase of the phylum Bacteroidetes and a decrease of Firmicutes and Proteobacteria. Among the most abundant bacterial families, S24-7 and Staphylococcaceae were expanded, whereas Lachnospiraceae were reduced during the early immune-priming phase of CIA. Several operational taxonomic units associated with S24-7 family increased, while those assigned to Lachnospiraceae and Ruminococcaceae decreased in the intestinal microbiota before the clinical onset of arthritis. The abundance of intestinal lamina propria Th17 cells significantly correlated with the severity of CIA; however, lamina propria Th1 cells were not correlated with arthritis. Elimination of intestinal microbiota during established arthritis specifically suppressed intestinal Th17 cell differentiation without affecting Th1 and regulatory T cells. Importantly, elimination of intestinal microbiota suppressed Th17 cell differentiation and IL-17 production in joint-draining lymph nodes, and reduced the severity of established CIA. In contrast, the T cell-independent serum-transfer arthritis was not affected by this strategy.

Conclusion:

These observations suggest that perturbations of the intestinal microbiome precede the development of inflammatory arthritis. Similar studies are warranted in human pre-RA or at-risk individuals to shed light on the potential relevance of the microbiome in the preclinical phase of RA. Our studies also suggest that modulation of the intestinal microbiota after the onset of arthritis may still provide opportunities to treat inflammatory arthritis.

Disclosure: R. Rogier, None; H. Evans-Marin, None; J. Manasson, None; P. M. van der Kraan, None; W. B. van den Berg, None; M. I. Koenders, None; J. U. Scher, NIAMS-NIH, 2; S. Abdollahi-Roodsaz, None.

To cite this abstract in AMA style:

Rogier R, Evans-Marin H, Manasson J, van der Kraan PM, van den Berg WB, Koenders MI, Scher JU, Abdollahi-Roodsaz S. Alteration of the Intestinal Microbiome in the Preclinical Phase of Experimental Arthritis and the Efficacy of Microbiota Modulation in Established Arthritis in Mice [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/alteration-of-the-intestinal-microbiome-in-the-preclinical-phase-of-experimental-arthritis-and-the-efficacy-of-microbiota-modulation-in-established-arthritis-in-mice/. Accessed .

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