Browsing by Subject "Prebiotics"
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Item 57437 Effects of Prebiotics on the Gut Microbiome Profile, Beta-cell Function and Immune Markers in Newly-Diagnosed Type 1 Diabetes(Cambridge University Press, 2021) Ismail, Heba M.; Evans-Molina, Carmella; DiMeglio, Linda A.; Pediatrics, School of MedicineABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.Item Does the Gut Microbiome Play a Role in Obesity in Type 1 Diabetes? Unanswered Questions and Review of the Literature(Frontiers Media, 2022-07-08) Ismail, Heba M.; Evans-Molina, Carmella; Pediatrics, School of MedicineEvidence suggests that type 1 diabetes (T1D) risk and progression are associated with gut bacterial imbalances. Children with either T1D or islet antibody positivity exhibit gut dysbiosis (microbial imbalance) characterized by lower gram-positive to gram-negative gut bacterial ratios compared to healthy individuals, leading to a pro-inflammatory milieu. In addition, specific gut microbiome changes, including increased virulence factors, elevated phage, prophage, and motility genes, and higher amplitude stress responses, have been identified in individuals who have or are progressing towards T1D. Additionally, gut microbiome differences are associated with and thought to contribute to obesity, a comorbidity that is increasingly prevalent among persons with T1D. Obesity in T1D is problematic because individuals with obesity progress faster to T1D, have reduced insulin sensitivity compared to their lean counterparts, and have higher risk of complications. Animal and human studies suggest higher relative abundance of bacterial taxa associated with changes in bile acid and short chain fatty acid biosynthesis in obesity. However, it is unknown to what extent the gut microbiome plays a role in obesity in T1D and these worse outcomes. In this review, we aim to evaluate potential gut microbiome changes and associations in individuals with T1D who are obese, highlighting the specific gut microbiome changes associated with obesity and with T1D development. We will identify commonalities and differences in microbiome changes and examine potential microbiota-host interactions and the metabolic pathways involved. Finally, we will explore interventions that may be of benefit to this population, in order to modify disease and improve outcomes.Item 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 MedicineObjective: 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.Item Evaluating the effect of prebiotics on the gut microbiome profile and β cell function in youth with newly diagnosed type 1 diabetes: protocol of a pilot randomized controlled trial(BMC, 2023-08-25) Ismail, Heba M.; Spall, Maria; Evans‑Molina, Carmella; DiMeglio, Linda A.; Pediatrics, School of MedicineIntroduction: Data show that disturbances in the gut microbiota play a role in glucose homeostasis, type 1 diabetes (T1D) risk and progression. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites favorably with an increase in bacteria producing short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity, and secretion in healthy non-diabetic adults. Additionally, a recent study testing an acetylated and butyrylated form of HAMS (HAMS-AB) that further increases SCFA production prevented T1D in a rodent model without adverse safety effects. The overall objective of this human study will be to assess how daily HAMS-AB consumption impacts the gut microbiome profile, SCFA production, β cell heath, function, and glycemia as well as immune responses in newly diagnosed T1D youth. Methods and analysis: We hypothesize that HAMS-AB intake will improve the gut microbiome profile, increase SCFA production, improve β cell health, function and glycemia as well as modulate the immune system. We describe here a pilot, randomized crossover trial of HAMS-AB in 12 newly diagnosed T1D youth, ages 11-17 years old, with residual β cell function. In Aim 1, we will determine the effect of HAMS-AB on the gut microbiome profile and SCFA production; in Aim 2, we will determine the effect of HAMS-AB on β cell health, function and glycemia; and in Aim 3, we will determine the peripheral blood effect of HAMS-AB on frequency, phenotype and function of specific T cell markers. Results will be used to determine the effect-size estimate of using HAMS-AB. We anticipate beneficial effects from a simple, inexpensive, and safe dietary approach. Ethics and dissemination: The Institutional Review Board at Indiana University approved the study protocol. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Abstracts will be submitted to relevant national and international conferences.Item Fructooligosaccharides act on the gut-bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice(Oxford University Press, 2024-02-21) Islam, Proapa; Ice, John A.; Alake, Sanmi E.; Adedigba, Pelumi; Hatter, Bethany; Robinson, Kara; Clarke, Stephen L.; Ford Versypt, Ashlee N.; Ritchey, Jerry; Lucas, Edralin A.; Smith, Brenda J.; Obstetrics and Gynecology, School of MedicineTargeting the gut-bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (P < .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, Sost, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.Item LBSUN309 The Effect Of Prebiotics In Newly Diagnosed Youth With Type 1 Diabetes (T1D)(Oxford University Press, 2022-11-01) Ismail, Heba; Evans-Molina, Carmella; DiMeglio, Linda A.; Pediatrics, School of MedicineAcetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic that is effective in T1D prevention in mouse models. It alters the gut microbiome profile towards bacterial fermenters with increases short chain fatty acids (SCFA) production which improves glycemia, insulin sensitivity and secretion. The objective of this pilot study is to assess the effect of oral HAMS-AB for 4 weeks on glycemia, microbial metabolite and SCFA production in newly diagnosed (<2 years of diagnosis) youth with T1D. Thus far, we have enrolled 7 subjects with 1 early drop out due to nausea secondary to the prebiotic. The mean±SD age in the remaining 6 was 14.4±1.8 yrs, diabetes duration 18.6±6.3 months, 4/6 were female and White, all with BMI of <85th%. The prebiotic was safe and well-tolerated in all 6 who remained in the study. We assessed glycemia changes pre and post-intervention and the percent time in range (TIR) from continuous glucose monitoring data over a 4 week period increased significantly: 61. 0% vs. 71.8%, X2 18.2, p=0. 001. Stool SCFA levels were measured in 4 subjects, and butyrate levels increased post-prebiotic (8.1±9.8 vs 22.6± 6.4mmol SCFA/kg fecal material, p=0. 047). Serum and plasma Hippurate levels (a microbial metabolite associated with increased gut bacterial diversity and improved glycemia) increased significantly after 4 weeks of prebiotic consumption compared to before in all 6 individuals (p=0. 028 for serum and p=0. 033 for plasma, respectively). In summary, the prebiotic HAMS-AB was safe in adolescents with T1D. It significantly increased the percent TIR, serum and plasma Hippurate levels and stool butyrate levels. Enrollment continues as collection of samples from more participants should allow for a more conclusive analysis.Item A Renal Clinician’s Guide to the Gut Microbiota(Elsevier, 2020-09) Snelson, Matthew; Biruete, Annabel; McFarlane, Catherine; Campbell, Katrina; Medicine, School of MedicineIt is increasingly recognized that the gut microbiota plays a role in the progression of chronic diseases and that diet may confer health benefits by altering the gut microbiota composition. This is of particular relevance for chronic kidney disease (CKD), as the gut is a source of uremic retention solutes, which accumulate as a result of impaired kidney function and can exert nephrotoxic and other harmful effects. Kidney dysfunction is also associated with changes in the composition of the gut microbiota and the gastrointestinal tract. Diet modulates the gut microbiota, and there is much interest in the use of prebiotics, probiotics, and synbiotics as dietary therapies in CKD, as well as dietary patterns that beneficially alter the microbiota. This review provides an overview of the gut microbiota and its measurement, its relevance in the context of CKD, and the current state of knowledge regarding dietary manipulation of the microbiota.Item Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism(Elsevier, 2023) Lambert, Kelly; Rinninella, Emanuele; Biruete, Annabel; Sumida, Keiichi; Stanford, Jordan; Raoul, Pauline; Mele, Maria Cristina; Wang, Angela Yee-Moon; Mafra, Denise; Medicine, School of MedicineThere is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.Item Understanding How Sex Influences the Impact of IL-10 on Bone Microarchitecture and Bone Metabolism Over Time(Elsevier, 2021) Price, Payton; Perez, Leo; Hatter, Bethany; Robinson, Kara; Islam, Proapa; Alake, Sanmi; Ice, John; Lucas, Edralin; Smith, Brenda; Obstetrics and Gynecology, School of MedicineObjectives: Dietary interventions with pre- and probiotics favorably affect the gut-bone axis, mediated in part by the anti-inflammatory cytokine, interleukin (IL)-10. This study sought to understand how IL-10’s impact on bone metabolism and microarchitecture differs with sex and time. Methods: Six-week-old B6.129P2-Il10tm1Cgn/J (KO) and C57BL/6 (WT) mice were assigned in a 2 × 2 × 2 factorial design with strain (WT & KO), sex, and time (3 & 6 m) as factors. Mice were fed AIN-93G diet for 3 m followed by AIN-93 M for the study duration. Dual-energy x-ray absorptiometry was used to assess bone mineral content (BMC) and density (BMD). Micro-computed tomography was used to assess femur and lumbar vertebrae trabecular and cortical bone. Serum procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1), bone formation and resorption markers respectively, were assessed by ELISA. Data were analyzed using ANOVA; p < 0.05 was considered significant. Results: Reductions in BMC and BMD (P < 0.05) in KO vs WT and at 3 vs 6 m were observed; a sex effect was found with reductions in BMC in KO females compared to KO males. Femoral trabecular bone volume (BV/TV) was lower (P < 0.05) in KO vs WT, females vs males, and at 6 vs 3 m. Trabecular thickness (TbTh) decreased (P < 0.05) in KO vs WT and increased from 3 to 6 m, while decreases in trabecular number (TbN) were greater (P < 0.05) in KO mice, females, and at 6 m compared to counterparts. Cortical area and thickness were decreased (P < 0.05) in KO vs WT and in females vs males, which was greater at 6 m, while cortical bone porosity was higher in KO vs WT and increased at 6 mo. Vertebral trabecular BV/TV was lower (P < 0.05) in KO vs WT at 3 and 6 m, with KO females showing reduced BV/TV (P < 0.05) from 3 to 6 m. Reduced TbTh and TbN were observed in KO vs WT, and females had increased (P < 0.05) TbTh and trabecular separation and reduced TbN. P1NP showed a time effect (P < 0.05) with reductions in WT females and males at 6 m compared to 3 m KO females (P < 0.05). CTX-1 shows a sex effect (P < 0.05) and a trending strain effect (P = 0.059), with elevated serum CTX-1 in 3 m KO males compared to WT and KO females at 6 m (P < 0.05). Conclusions: While IL-10 plays an important role in maintaining both trabecular and cortical bone, it may have a more protective effect on the cortical bone of female mice over time.