Background/Purpose: Increased intestinal permeability (IP) is common in chronic inflammatory diseases, and can be measured indirectly (e.g., with blood markers such as lipopolysaccharide, LPS), or directly (through measurement of ingested and excreted sugars). The goal was to determine cross-sectional associations between directly measured IP and radiographic multiple joint osteoarthritis (rMJOA) in community cohorts of humans and pet dogs.

Methods: Data were from the Johnston County Health Study (JoCoHS) and a parallel study in pet dogs from North Carolina State University (NCSU). JoCoHS participants (n=96, mean age 55 yrs, 63% females, 57% White) provided radiographs, clinical, and demographic data. Similar data were collected from an independent cohort of pet dogs (N&#3f110, mean age 8 yrs). rMJOA was defined as 3+ unique appendicular joint sites involved in both cohorts.For direct IP assessment, humans fasted overnight followed by ingestion of 10g lactulose and 5g 12C-mannitol; sugars excreted in urine at baseline, 3- and 5-hours post-ingestion were measured using high-performance liquid chromatography (HPLC)–tandem mass spectrometry (Mayo). Lactulose:mannitol (L:M) ratio was calculated based on the percentage of administered dose of each sugar molecule in urine at 3- and 5-hours post-ingestion. IP in dogs was also assessed after an overnight fast, followed by oral iohexol at a dose of 2.0 mL/kg (Omnipaque-350, GE Healthcare Ireland, Ireland). HPLC was used to analyze iohexol concentration in serum at baseline, 1, 2, and 4 hours post-iohexol ingestion (NCSU).Sugars excreted at each time point and L:M at 5 hours in humans, and iohexol absorbed in dogs, were evaluated for participants with and without rMJOA using boxplots, comparing those with and without MJOA and by number of sites with rOA. Regression models adjusted for sex, age, body mass index (BMI), Charlson Index, and medications were used to examine the association of the mannitol excretion (log transformed) at 5 hours with rMJOA in humans; a similar approach used body composition score (BCS), age and rMJOA status in pet dogs.

Results: The overall prevalence of increased IP (L:M ≥ 0.1, PMID33865841) was low in JoCoHS participants. The expected associations between IP (L:M ratio) and LPS, age, and BMI were seen in humans, indicating that the test performed as expected (data not shown). Mannitol excretion was slightly higher in those with rMJOA at 3 and 5 hours (Fig1). In regression models, mannitol excretion at 5 hours was lower in women but not statistically significantly associated with rMJOA (Table 1). In dogs, higher serum iohexol was not associated with BCS (a measure of obesity), age, or rMJOA status. IP measured by serum iohexol was numerically but not significantly increased at 4 hours (Fig1). IP (L:M ratio at 5 hours for humans; total time-integrated serum iohexol at 4 hours in dogs) was increased when more joint sites were involved (Fig2).

Conclusion: No associations were observed between increased IP and rMJOA in humans or pet dogs, likely due to limited sample size and cross-sectional data. Increased IP was infrequent in both cohorts, although a few outliers were noted (primarily in individuals with comorbidities and medication use).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/direct-assessment-of-intestinal-permeability-as-a-risk-factor-for-multiple-joint-osteoarthritis-in-community-cohorts-of-humans-and-pet-dogs/