Objective The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. In this study we used a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model. Methods We have isolated a commensal bacterium, Prevotella histicola, native to the human gut that has systemic immune effects when administered enterally. Arthritis-susceptible HLA-DQ8 mice were immunized with type II collagen and treated with P. histicola; disease incidence, onset and severity were monitored. Changes in the gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice. Results DQ8 mice when treated with P. histicola in prophylactic or therapeutic protocols exhibited significantly decreased incidence and severity of arthritis as compared to controls. The microbial mucosal modulation of arthritis was dependent on the regulation by CD103+ dendritic cells and myeloid suppressors, CD11b+Gr-1, and by generation of T regulatory cells, CD4+CD25+FoxP3+, in the gut, resulting in suppression of antigen-specific Th17 response and increased transcription of IL-10. Treatment with P. histicola led to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins, Zo-1 and Occludin. However, the innate immune response via TLR4 and TLR9 were not affected in treated mice. Discussion Our results demonstrate that enteral exposure to P. histicola suppresses arthritis via mucosal regulation. P. histicola is a unique commensal that can be explored as a novel therapy for RA and may have low/no side effects.

Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.

Background: Celiac disease (CD) often presents with symptoms of diarrhea and malabsorption, termed classical CD. However, it can also present as nonclassical CD, which is commonly associated with nongastrointestinal symptoms. Studies suggest that nonclassical CD tends to have less severe symptoms than classical CD, which may affect both adherence to a gluten-free diet (GFD) and psychological stress. Therefore, we compared adherence to a GFD and psychological measures, including quality of life (QOL) and somatization, between patients with nonclassical and classical presentations of CD. Methods: Patients at a tertiary care center with biopsy-proven CD, who completed a Talley Bowel Disease Questionnaire and the Short Form-36 at diagnosis and who had been on a GFD for at least 1 year, were included in this study. Patients were further surveyed to assess gastrointestinal symptoms, QOL, Somatization Symptom Checklist (SSC), and adherence to a GFD. Results were compared between patients with classical versus nonclassical CD presentation. Results: Among 122 patients included in this study, 62 had classical CD and 60 had nonclassical CD. At diagnosis, health-related QOL was lower in the classical CD group than in the nonclassical CD group. After following a GFD, both groups had improved QOL after following a GFD, and body mass index significantly increased in both groups. Most subscales of QOL, SSC scores, and adherence to the GFD were similar between the groups, except the Short Form-36 Mental Component summary scores that were still lower in the classical CD (48.4 vs. 52.6 nonclassical CD group; P=0.03). Conclusions: Despite QOL at diagnosis being higher in those with nonclassical CD versus lower in those with classical CD, both groups had improved QOL and achieved a similar QOL after following a GFD.

Background: Medial meniscus posterior root tears (MMPRTs) cause pain and dysfunction and are associated with poor clinical outcomes with nonoperative management at short-term follow-up. However, little is known about the long-term natural history of these tears. Purpose: The purpose of this study was to (1) provide an update to a previous minimum 2-year study on the natural progression of these tears and (2) evaluate long-term patient-reported and radiographic outcomes. Study Design: Case series (prognosis); Level of evidence, 4. Methods: A retrospective review was performed on a cohort of patients with untreated MMPRTs, diagnosed between 2005 and 2013, who were followed clinically using International Knee Documentation Committee (IKDC), visual analog scale for pain, and Tegner activity scores as well as radiographically at a minimum 10-year follow-up. Failure was defined as conversion to arthroplasty or a severely abnormal subjective IKDC score <75.4. Results: Overall, 5 (10%) of the original 52 patients with minimum 2-year outcomes were subsequently lost to follow-up. The remaining 47 patients (21 male, 26 female) were followed for a mean of 14 ± 2 years (range, 11-18 years). At final follow-up, 25 patients (53%) had progressed to total knee arthroplasty, 8 (17%) were deceased, and 14 (30%) had not progressed to total knee arthroplasty. The mean IKDC and Tegner activity scores for the 14 patients with remaining MMPRTs were 51.6 ± 22.2 and 3.1 ± 1.1, respectively, and the mean visual analog scale score was 4.4 ± 3.0. Radiographically, the mean Kellgren-Lawrence grade progressed from 1.2 ± 0.7 at baseline to 2.6 ± 0.5 at final follow-up ( P < .001). At a minimum 10-year follow-up, 37 of 39 living patients (95%) had failed nonoperative treatment. Conclusion: Poor clinical and radiographic outcomes were associated with the nonoperative treatment of degenerative MMPRTs at long-term follow-up. This study provides a valuable update on the natural history and long-term prognosis of nonoperatively treated MMPRTs.