Browsing by Subject "Dietary fiber"

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    547 The viscous and fermentability properties of dietary fiber impact on chronic kidney disease-mineral and bone disorder
    (Cambridge University Press, 2024-04-03) Biruete, Annabel; Chen, Neal X.; Srinivasan, Shruthi; O’Neill, Kalisha; Siles, Samantha; Hill Gallant, Kathleen; Moe, Sharon M.; Medicine, School of Medicine
    OBJECTIVES/GOALS: Dietary fiber has been used in other clinical populations to improve mineral disorders, but there is limited data in chronic kidney disease, despite the high prevalence of mineral and bone disorder (known as CKD-MBD). Our objective was to evaluate the effect of dietary fiber based on viscosity and fermentability on CKD-MBD outcomes. METHODS/STUDY POPULATION: 22-week-old male CKD rats (mild-to-moderate CKD) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) Inulin (+fermentability, -viscosity), 3) Psyllium husk (-fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure). Rats were placed in metabolic cages for 3 consecutive days the last week before euthanasia for mineral balance. At euthanasia, blood, tibia, heart, and aorta were collected for CKD-MBD assessment. Additional tissues collected included kidneys and all intestinal segments. RESULTS/ANTICIPATED RESULTS: Our preliminary data indicates that weight trajectories and survival were similar between treatment groups. At 33 weeks of age, kidney weight index (an indirect measurement of kidney function as this animal model develops polycystic kidneys) was lower in the psyllium-treated rats compared to all of the other treatments. Plasma phosphorus was lower with Psyllium and Pectin compared to Cellulose-treated rats. Left ventricular mass index was lower in the Inulin, Psyllium, and Pectin-treated rats compared to the Cellulose-treated rats. Ongoing tissue analyses include biochemical markers of mineral and bone metabolism (parathyroid hormone, fibroblast growth factor-23, and phosphorus balance), bone parameters (dynamic histomorphometry and microCT), and cardiovascular calcification. DISCUSSION/SIGNIFICANCE: Our preliminary data indicate that dietary fiber based on fermentability and viscosity impacts CKD-MBD outcomes and may be an innovative, low-cost intervention that can be trialed in people with CKD for the prevention and treatment of CKD-MBD.
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    Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women
    (Nature Research, 2018-11-20) Dugas, Lara R.; Bernabé, Beatriz Peñalver; Priyadarshini, Medha; Fei, Na; Park, Seo Jin; Brown, Laquita; Plange-Rhule, Jacob; Nelson, David; Toh, Evelyn C.; Gao, Xiang; Dong, Qunfeng; Sun, Jun; Kliethermes, Stephanie; Gottel, Neil; Luke, Amy; Gilbert, Jack A.; Layden, Brian T.; Microbiology and Immunology, School of Medicine
    We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m2) and 50% obese (BMI ≥ 30 kg/m2)] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.
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    The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD
    (Oxford University Press, 2023-12-07) Biruete, Annabel; Chen, Neal X.; Metzger, Corinne E.; Srinivasan, Shruthi; O’Neill, Kalisha; Fallen, Paul B.; Fonseca, Austin; Wilson, Hannah E.; de Loor, Henriette; Evenepoel, Pieter; Swanson, Kelly S.; Allen, Matthew R.; Moe, Sharon M.; Anatomy, Cell Biology and Physiology, School of Medicine
    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.