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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 Microbiologic Approaches to Treating Inflammatory Bowel Disease(Millennium Medical Publishing, 2021-08) Fischer, Monika; Medicine, School of MedicineItem Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial(MDPI, 2021-05-05) Kong, Xue-Jun; Liu, Jun; Liu, Kevin; Koh, Madelyn; Sherman, Hannah; Liu, Siyu; Tian, Ruiyi; Sukijthamapan, Piyawat; Wang, Jiuju; Fong, Michelle; Xu, Lei; Clairmont, Cullen; Jeong, Min-Seo; Li, Alice; Lopes, Maria; Hagan, Veronica; Dutton, Tess; Chan, Suk-Tak (Phoebe); Lee, Hang; Kendall, Amy; Kwong, Kenneth; Song, Yiqing; Epidemiology, School of Public HealthAutism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.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.