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Item The Application of Metabolomics to Probiotic and Prebiotic Interventions in Human Clinical Studies(MDPI, 2020-03) O’Connell, Thomas M.; Otolaryngology -- Head and Neck Surgery, School of MedicineThere is an ever-increasing appreciation for our gut microbiota that plays a crucial role in the maintenance of health, as well as the development of disease. Probiotics are live bacteria that are consumed to increase the population of beneficial bacteria and prebiotics are dietary substrates intended to promote the propagation of beneficial bacteria. In order to optimize the use of probiotics and prebiotics, a more complete biochemical understanding of the impact that these treatments have on the community and functioning of the gut microbiota is required. Nucleic acid sequencing methods can provide highly detailed information on the composition of the microbial communities but provide less information on the actual function. As bacteria impart much of their influence on the host through the production of metabolites, there is much to be learned by the application of metabolomics. The focus of this review is on the use of metabolomics in the study of probiotic and prebiotic treatments in the context of human clinical trials. Assessment of the current state of this research will help guide the design of future studies to further elucidate the biochemical mechanism by which probiotics and prebiotics function and pave the way toward more personalized applications.Item Manipulating the microbiome to enhance oral tolerance in food allergy(Elsevier, 2022-12) Gonzalez-Visiedo, Miguel; Kulis, Michael D.; Markusic , David M.; Pediatrics, School of MedicineLoss of oral tolerance (OT) to food antigens results in food allergies. One component of achieving OT is the symbiotic microorganisms living in the gut (microbiota). The composition of the microbiota can drive either pro-tolerogenic or pro-inflammatory responses against dietary antigens though interactions with the local immune cells within the gut. Products from bacterial fermentation, such as butyrate, are one of the main communication molecules involved in this interaction, however, this is released by a subset of bacterial species. Thus, strategies to specifically expand these bacteria with protolerogenic properties have been explored to complement oral immunotherapy in food allergy. These approaches either provide digestible biomolecules to induce beneficial bacteria species (prebiotics) or the direct administration of live bacteria species (probiotics). While this combined therapy has shown positive outcomes in clinical trials for cow's milk allergy, more research is needed to determine if this therapy can be extended to other food allergens.Item Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome(Wiley, 2018-12) Connell, Mary; Shin, Andrea; James-Stevenson, Toyia; Xu, Huiping; Imperiale, Thomas F.; Herron, Jennifer; Medicine, School of MedicineBackground: VSL#3 is a patented probiotic for which several clinical trials suggest benefits on motor function, bloating and symptoms of irritable bowel syndrome (IBS). Objectives: To quantify effects of VSL#3 on abdominal pain, stool consistency, overall response, abdominal bloating, and quality of life (QOL) in IBS through meta-analysis. Methods: MEDLINE (OvidSP and PubMed), EMBASE, Web of Science, and Scopus were searched up to May 2017. Using a fixed effects model, we pooled data from intention-to-treat analyses of randomized trials (RCTs) comparing VSL#3 to placebo in IBS. Data were reported as relative risk (RR), overall mean difference (MD) or standardized MD (SMD) with 95% confidence intervals (CI). Quality of evidence was rated using the GRADE approach. Key Results: Among 236 citations, five RCTs (243 patients) were included. No significant differences were observed for abdominal pain (SMD = −0.03; 95% CI −0.29–0.22), bloating (SMD = −0.15; 95% CI −0.40–0.11), proportion of bowel movements with normal consistency (overall MD = 0; 95% CI −0.09–0.08), or IBS-QOL (SMD = 0.08; 95% CI −0.22–0.39). VSL#3 was associated with a nearly statistically significant increase in overall response (RR=1.39; 95% CI 0.99–1.98). Conclusions & Inferences: In this systematic review and meta-analysis, there was a trend towards improvement in overall response with VSL#3, but no clear evidence effectiveness for IBS. However, the number and sample sizes of the trials are small and the overall quality of evidence for three of the five outcomes was low. Larger trials evaluating validated endpoints in well-defined IBS patients are warranted.Item Unraveling the role of the microbiome in chronic rhinosinusitis(Elsevier, 2022) Psaltis, Alkis J.; Wagner Mackenzie, Brett; Cope, Emily K.; Ramakrishnan, Vijay R.; Otolaryngology -- Head and Neck Surgery, School of MedicineChronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research.