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Life sciences · Journal article
Frontiers in Molecular Medicine · November 2, 2026
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Background Human Immunodeficiency Virus (HIV) infection is associated with increased gut permeability resulting in chronic inflammation and elevated levels of zonulin. An optimum diet including fiber has been demonstrated in some cohorts to support a healthy gut microbiome, decrease gut permeability, decrease systemic inflammation, and reduce the risk of developing metabolic disorders. A previous study documented multiple benefits of inulin supplementation in obese/overweight subjects. This pilot study assessed the same soluble fiber supplementation in subjects with-controlled HIV infection and acquired metabolic conditions on zonulin levels and metabolic parameters. Materials/Methods Ten participants with well-controlled HIV infection with at least three acquired metabolic disorders were enrolled in the study. Each subject had an initial 1-week lead in period of 12 g orally once daily of the soluble fiber inulin then twice daily for the 42-day study duration. Baseline and post-intervention zonulin levels were analyzed along with various markers of metabolic syndrome. Results Fiber supplementation was well tolerated. Flatulence and abdominal bloating were experienced by some subjects. There was no significant difference between baseline and post-intervention levels for Body Mass Index (BMI), Hemoglobin A1C (HbA1c), fructosamine or lipid levels. Each subject had an increase in zonulin levels. Median zonulin levels at baseline were 177.9 μg/mL (Interquartile Range [IQR] 97.8-268.6), increasing to post-intervention levels of 532.4 μg/mL (IQR 289.7-1532.70) which was statistically significant (p = 0.002). Conclusion In contrast to the experience with other patient populations, inulin supplementation was associated with a significant increase in zonulin levels, an indirect biomarker of gut permeability. There were no changes in metabolic parameters. We speculate that underlying pre-existing gut dysbiosis in persons with well-controlled HIV with metabolic disorders may complicate dietary strategies to optimize health. Short term soluble fiber supplementation had no demonstrable benefit in this small sample. Further investigations including direct measures of gut permeability, metabolomics and serial microbiome assessment and additional dietary strategies are needed.