Browsing by Author "Xavier, Ramnik J."

Now showing 1 - 3 of 3
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    Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course
    (Elsevier, 2018-10-10) Schirmer, Melanie; Denson, Lee; Vlamakis, Hera; Franzosa, Eric A.; Thomas, Sonia; Gotman, Nathan M.; Rufo, Paul; Baker, Susan S.; Sauer, Cary; Markowitz, James; Pfefferkorn, Marian; Oliva-Hemker, Maria; Rosh, Joel; Otley, Anthony; Boyle, Brendan; Mack, David; Baldassano, Robert; Keljo, David; LeLeiko, Neal; Heyman, Melvin; Griffiths, Anne; Patel, Ashish S.; Noe, Joshua; Kugathasan, Subra; Walters, Thomas; Huttenhower, Curtis; Hyams, Jeffrey; Xavier, Ramnik J.; Medicine, School of Medicine
    Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care
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    Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles
    (Springer Nature, 2023) Morton, James T.; Jin, Dong-Min; Mills, Robert H.; Shao, Yan; Rahman, Gibraan; McDonald, Daniel; Zhu, Qiyun; Balaban, Metin; Jiang, Yueyu; Cantrell, Kalen; Gonzalez, Antonio; Carmel, Julie; Frankiensztajn, Linoy Mia; Martin-Brevet, Sandra; Berding, Kirsten; Needham, Brittany D.; Zurita, María Fernanda; David, Maude; Averina, Olga V.; Kovtun, Alexey S.; Noto, Antonio; Mussap, Michele; Wang, Mingbang; Frank, Daniel N.; Li, Ellen; Zhou, Wenhao; Fanos, Vassilios; Danilenko, Valery N.; Wall, Dennis P.; Cárdenas, Paúl; Baldeón, Manuel E.; Jacquemont, Sébastien; Koren, Omry; Elliott, Evan; Xavier, Ramnik J.; Mazmanian, Sarkis K.; Knight, Rob; Gilbert, Jack A.; Donovan, Sharon M.; Lawley, Trevor D.; Carpenter, Bob; Bonneau, Richard; Taroncher-Oldenburg, Gaspar; Anatomy, Cell Biology and Physiology, School of Medicine
    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.
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    Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response
    (Springer Nature, 2019-01-03) Haberman, Yael; Karns, Rebekah; Dexheimer, Phillip J.; Schirmer, Melanie; Somekh, Judith; Jurickova, Ingrid; Braun, Tzipi; Novak, Elizabeth; Bauman, Laura; Collins, Margaret H.; Mo, Angela; Rosen, Michael J.; Bonkowski, Erin; Gotman, Nathan; Marquis, Alison; Nistel, Mason; Rufo, Paul A.; Baker, Susan S.; Sauer, Cary G.; Markowitz, James; Pfefferkorn, Marian D.; Rosh, Joel R.; Boyle, Brendan M.; Mack, David R.; Baldassano, Robert N.; Shah, Sapana; Leleiko, Neal S.; Heyman, Melvin B.; Grifiths, Anne M.; Patel, Ashish S.; Noe, Joshua D.; Aronow, Bruce J.; Kugathasan, Subra; Walters, Thomas D.; Gibson, Greg; Thomas, Sonia Davis; Mollen, Kevin; Shen-Orr, Shai; Huttenhower, Curtis; Xavier, Ramnik J.; Hyams, Jeffrey S.; Denson, Lee A.; Pediatrics, School of Medicine
    Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.