Effects of dietary fiber on vascular calcification by repetitive diet-induced fluctuations in plasma phosphorus in early-stage chronic kidney disease rats

Tani, Makoto; Tanaka, Saburo; Takamiya, Kana; Kato, Yoji; Harata, Gaku; He, Fang; Sakaue, Motoyoshi; Ito, Mikiko

doi:10.3164/jcbn.20-46

Cited by 6 publications

(6 citation statements)

References 51 publications

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“…Several previous investigations demonstrated abnormal microbial community structures in rats with vascular calcification and chronic kidney disease [ 27 , 46 ]. Here, in our study, we detected the gut microbiota composition of VDN-treated rats by 16S RNA sequencing analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been reported in previous research that rats at an early stage of chronic kidney disease supplemented with dietary fibre, a precursor substance of SCFAs, can suppress the progression of vascular calcification. The authors suggested that the protective effects on blood vessels are attributed to SCFA reduction of uraemia toxin levels derived from intestinal bacteria [ 46 ]. In addition, the gut microbiota provides an important structural basis for the gut microbial barrier, and a healthy gut microbiota promotes the maintenance of gut barrier function.…”

Section: Discussionmentioning

confidence: 99%

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Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling

et al. 2022

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Background Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. Methods In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. Results The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. Conclusions Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling

et al. 2022

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“…It is conceivable that the inulin induced increase in FGF23 at 30 weeks led to a reduction in PTH at 32 weeks with enhanced urinary phosphate excretion. However, a previous study in unilateral nephrectomy rats given partially hydrolyzed guar gum (minimally viscous, fermentable fiber) and found a decrease in urinary phosphate excretion 57 , going against this potential explanation. We did not see a change in serum calcium to account for the changes in PTH, although we measured total calcium.…”

Section: Discussionmentioning

confidence: 87%

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

Moe

Biruete

Chen

et al. 2023

Preprint

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Background: Dietary 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. Methods: The 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. Results: In 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. Conclusions: The 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.

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“…It is conceivable that the inulin induced increase in FGF23 at stage 4 led to a reduction in PTH at stage 5 with enhanced urinary phosphate excretion. A previous study in unilateral nephrectomy rats given partially hydrolyzed guar gum (minimally viscous, fermentable fiber) found a decrease in urinary phosphate excretion, [ 53 ] going against this potential explanation. We did not see a change in serum calcium to account for the changes in PTH, although we measured total calcium.…”

Section: Discussionmentioning

confidence: 99%

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease–Mineral Bone Disorder (CKD‐MBD) in a Rat Model of CKD

Biruete,

Chen,

Metzger

et al. 2023

JBMR Plus

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Chronic kidney disease (CKD)–mineral bone disorder (CKD‐MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD‐MBD is unknown. To determine the effect of fiber on CKD‐MBD, we fed the Cy/+ rat with progressive CKD 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; CKD 4 and 5). We assessed CKD‐MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut‐derived uremic toxins. Results were analyzed by two‐way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor‐23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short‐chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD‐MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut‐derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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Effects of dietary fiber on vascular calcification by repetitive diet-induced fluctuations in plasma phosphorus in early-stage chronic kidney disease rats

Cited by 6 publications

References 51 publications

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling

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

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease–Mineral Bone Disorder (CKD‐MBD) in a Rat Model of CKD

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