The Dietary Fermentable Fiber Inulin Alters the Intestinal Microbiome and Improves Chronic Kidney Disease Mineral-Bone Disorder in a Rat Model of CKD

Moe, S. M.; Biruete, A.; Chen, N. X.; Metzger, C. E.; Srinivasan, S.; O'Neill, K.; Fallen, P.; Fonseca, A. D.; Wilson, H. E.; Evenepoel, P.; Swanson, K. S.; de Loor, H.; Allen, M. A.

doi:10.1101/2023.01.29.526093

bioRxiv · 10.1101/2023.01.29.526093

The Dietary Fermentable Fiber Inulin Alters the Intestinal Microbiome and Improves Chronic Kidney Disease Mineral-Bone Disorder in a Rat Model of CKD

Moe, S. M.·Biruete, A.·Chen, N. X.·Metzger, C. E.·Srinivasan, S.·O'Neill, K.·Fallen, P.·Fonseca, A. D.·Wilson, H. E.·Evenepoel, P.·Swanson, K. S.·de Loor, H.·Allen, M. A.

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Abstract

BackgroundDietary fiber is important for a healthy diet, but intake is low in CKD patients and the impact this has on the manifestations of CKD-Mineral Bone Disorder (MBD) is unknown. MethodsThe Cy/+ rat with progressive CKD was fed a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30 and ~15 % of normal kidney function). We assessed CKD-MBD, cecal microbiota, and serum gut-derived uremic toxins. Two-way ANOVA was used to evaluate the effect of age and inulin diet, and their interaction. ResultsIn CKD animals, dietary inulin led to changes in microbiota alpha and beta diversity at 30 and 32 weeks, with higher relative abundance of several taxa, including Bifidobacterium and Bacteroides, and lower Lactobacillus. Inulin reduced serum levels of gut-derived uremic toxins, phosphate, and parathyroid hormone, but not fibroblast growth factor-23. Dietary inulin decreased aorta and cardiac calcification and reduced left ventricular mass index and cardiac fibrosis. Bone turnover and cortical bone parameters were improved with inulin; however, bone mechanical properties were not altered. ConclusionsThe addition of the fermentable fiber inulin to the diet of CKD rats led to changes in the gut microbiota composition, lowered gut-derived uremic toxins, and improved most parameters of CKD-MBD. Future studies should assess this fiber as an additive therapy to other pharmacologic and diet interventions in CKD. Significance StatementDietary fiber has well established beneficial health effects. However, the impact of fermentable dietary fiber on the intestinal microbiome and CKD-MBD is poorly understood. We used an animal model of progressive CKD and demonstrated that the addition of 10% of the fermentable fiber inulin to the diet altered the intestinal microbiota and lowered circulating gut-derived uremic toxins, phosphorus, and parathyroid hormone. These changes were associated with improved cortical bone parameters, lower vascular calcification, and reduced cardiac hypertrophy, fibrosis and calcification. Taken together, dietary fermentable fiber may be a novel additive intervention to traditional therapies of CKD-MBD.

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Moe, S. M., Biruete, A., Chen, N. X., Metzger, C. E., Srinivasan, S., O'Neill, K., Fallen, P., Fonseca, A. D., Wilson, H. E., Evenepoel, P., Swanson, K. S., de Loor, H., Allen, M. A.. 2023-01-31. The Dietary Fermentable Fiber Inulin Alters the Intestinal Microbiome and Improves Chronic Kidney Disease Mineral-Bone Disorder in a Rat Model of CKD. https://doi.org/10.1101/2023.01.29.526093

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