Browsing by Author "Cross, Tzu-Wen L."

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    Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study
    (Elsevier, 2021) Biruete, Annabel; Cross, Tzu-Wen L.; Allen, Jacob M.; Kistler, Brandon M.; de Loor, Henriette; Evenepoel, Pieter; Fahey, George C., Jr.; Bauer, Laura; Swanson, Kelly S.; Wilund, Kenneth R.; Medicine, School of Medicine
    Objective: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD. Design and methods: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate. Results: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate. Conclusions: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.
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    Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut
    (Wiley, 2025) Milhouse, Wynne; Clapp Organski, Anna; Sun, Xun; Ai, Derek; Zhou, Baohua; Cross, Tzu-Wen L.; Ren, Hongxia; Pediatrics, School of Medicine
    The gut microbiome (GMB) regulates digestion, metabolism, immunity, and energy homeostasis. This study investigates how gut microbiota integrate the regulation in the neuroendocrine and enteroendocrine systems, with a focus on G protein-coupled receptors (GPCRs) in the brain-gut axis and sex differences. Germ-free (GF) mice exhibited increased hypothalamic expression of the anorexigenic neuropeptide and decreased expression of the negative regulator of leptin signaling. GF males had significantly lower serum leptin levels compared to conventional (CON) males, highlighting a potential link between the microbiome and leptin resistance. In the gut, GF mice demonstrated heightened expression of anorexigenic gut hormones, including peptide YY (Pyy) and cholecystokinin (Cck), in addition to increased levels of G protein-coupled receptors (GPCRs) involved in gut hormone secretion and nutrient metabolism, particularly in females. While carbohydrate metabolism genes were upregulated in CON mice, lipid metabolism genes were predominantly higher in GF mice. These findings suggest that the gut microbiota downregulates genes involved in appetite suppression, modulates GPCRs linked to gut hormone secretion, and contributes to leptin resistance, particularly in males. This research underscores the importance of the gut microbiome in host metabolism and reveals potential molecular targets for novel treatments of metabolic diseases.