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Item Effect of Advanced HIV Infection on the Respiratory Microbiome(ATS Journals, 2016-07-15) Twigg, Homer L., III; Knox, Kenneth S.; Zhou, Jin; Crothers, Kristina A.; Nelson, David E.; Toh, Evelyn; Day, Richard B.; Lin, Huaiying; Gao, Xiang; Dong, Qunfeng; Mi, Deming; Katz, Barry P.; Sodergren, Erica; Weinstock, George M.; Medicine, School of MedicineRATIONALE: Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. OBJECTIVES: To measure the lung microbiome in an HIV-infected population with advanced disease. METHODS: 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. MEASUREMENTS AND MAIN RESULTS: The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. CONCLUSIONS: The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.Item SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)(MDPI, 2022-09-10) Khanna, Sahil; Sims, Matthew; Louie, Thomas J.; Fischer, Monika; LaPlante, Kerry; Allegretti, Jessica; Hasson, Brooke R.; Fonte, Allyson T.; McChalicher, Christopher; Ege, David S.; Bryant, Jessica A.; Straub, Timothy J.; Ford, Christopher B.; Henn, Matthew R.; Wang, Elaine E.L.; von Moltke, Lisa; Wilcox, Mark H.; Medicine, School of MedicineClostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20−25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response.Item Starchy and fibrous feedstuffs differ in their in vitro digestibility and fermentation characteristics and differently modulate gut microbiota of swine(Springer, 2022-05-03) Tiwari, Utsav P.; Mandal, Rabindra K.; Neupane, Kabi Raj; Mishra, Birendra; Jha, Rajesh; Pediatrics, School of MedicineBackground Alternative feedstuffs may contribute to reducing feed costs of pig production. But these feedstuffs are typically rich in fiber and resistant starch (RS). Dietary fibers and RS are fermented in the gastrointestinal tract (GIT) and modulate the microbial community. Certain microbes in the GIT can promote host health, depending on the type of fermentation substrates available. In this study, six alternative feedstuffs (three starchy: Okinawan sweet potato, OSP; yam, and taro, and three fibrous: wheat millrun, WMR; barley brewers grain, BBG; and macadamia nut cake, MNC) were evaluated for their in vitro digestibility and fermentation characteristics and their effects on pig’s hindgut microbial profile. After 2 steps of enzymatic digestion assay, residues were fermented using fresh pig feces as microbial inoculum, and gas production was recorded periodically for 72 h and modeled for fermentation kinetics. After fermentation, the residual liquid phase was analyzed for short-chain fatty acid (SCFA), and the solid phase was used to determine the nutrient’s digestibility and microbial community. Results In vitro ileal digestibility of dry matter and gross energy was higher in starchy than fibrous feedstuffs. Total gas and SCFA production were significantly higher (P < 0.001) in starchy feedstuffs than fibrous feedstuffs. Both acetate and propionate production was significantly higher (P < 0.001) in all starchy feedstuffs than BBG and MNC; WMR was in between. Overall alpha diversity was not significantly different within and between starchy and fibrous feedstuffs. Beta diversity (measured using bray Curtis dissimilarity distance) of starchy feedstuffs was significantly different (P < 0.005) than fibrous feedstuffs. Conclusion Starchy feedstuffs acted as a substrate to similar types of microbes, whereas fibrous feedstuffs resulted in a more diverse microbial population. Such alternative feedstuffs may exert comparable beneficial effects, thus may be included in swine diets to improve gut health.