Background/Purpose: The 16-week Plants for Joints (PFJ) intervention, consisting of a whole-food plant-based diet, physical activity, and stress management, significantly reduced 28-joint Disease Activity Score (DAS28) in people with rheumatoid arthritis (RA) compared to standard care.^1,2 The mucosal origins hypothesis suggests RA is triggered at mucosal sites in genetically predisposed individuals,³ and then transitions to the synovial joints.⁴ Also, studies indicate fiber ingestion supports gut barrier health, thereby reducing inflammation.⁵ This study aims to assess the integrity of the gut barrier and identify key metabolites, aiming to discover potential mechanistic pathways linking the intervention to its observed clinical effects.

Methods: Stool and blood samples were collected at baseline and 16 weeks. Fecal albumin and calprotectin levels were measured by ELISA in all 77 participants. Untargeted metabolomics were performed on plasma samples from 30 participants with the greatest DAS28 change during the intervention and 10 control group participants with stable DAS28 using high resolution mass spectrometry coupled to liquid chromatography. Between-group differences at 16-weeks in albumin and calprotectin were evaluated with linear regression adjusted for baseline values. Within-group differences and correlations with DAS28 were evaluated using the Mann-Whitney U test and Spearman’s Rank Correlation Coefficient, respectively. Student’s t-test compared log10-transformed signal areas for metabolomic data.

Results: Within the intervention group fecal albumin levels decreased significantly compared to the start (p = 0.027), with no significant difference between groups at the end of the trial (p = 0.28; Figure 1a). A significant association was found between the DAS28 fold change and albumin in the intervention group (r = 0.5, p < 0.001; Figure 2a). Fecal calprotectin was not significantly different between intervention and control groups at 16-weeks (p = 0.95) or within the intervention group (p = 0.12; Figure 1b). The DAS28 change was not significantly associated with calprotectin in the intervention group (Figure 2b). The major metabolite increased in the best responders to the intervention was lenticin (log2 fold change 1.32, p < 0.0001; Figure 1c). The best responders also had decreased levels of tryptophan (log2 fold change –0.12, p = 0.03; Figure 1d). Changes in lenticin and tryptophan were not correlated with changes in DAS28 (Figure 2c,d).

Conclusion: The intervention improved intestinal barrier integrity, measured with fecal albumin, increased lenticin levels and decreased tryptophan levels. Lenticin is a lentil intake biomarker shown to be protective against LPS-induced inflammation and osteoclastic differentiation,^6,7 while indole, a bacterial-derived tryptophan metabolite, has been linked to experimental arthritis development.⁸ These preliminary findings introduce potential mechanistic pathways linking the intervention to its observed clinical effects, warranting further investigation into gut barrier integrity, microbiome, and metagenomic testing.

References (PMID):

1. 34663431
2. 36617162
3. 30111803
4. 33674813
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6. 28420166
7. 29136954
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/possible-mechanistic-pathways-of-the-effective-plants-for-joints-lifestyle-and-dietary-intervention-for-rheumatoid-arthritis/