Bachelor of Science, Allegheny College (2012)
Doctor of Philosophy, University of Vermont (2018)
Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation.
Cell host & microbe
Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.
View details for DOI 10.1016/j.chom.2020.01.021
View details for PubMedID 32101703
Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets.
American journal of physiology. Gastrointestinal and liver physiology
Intestinal functions, including motility and secretion, are locally controlled by enteric neural networks housed within the wall of the gut. The fidelity of these functions depends on the precision of intercellular signaling amongst cellular elements, including enteric neurons, epithelial cells, immune cells, and glia, all of which are vulnerable to disruptive influences during inflammatory events. This review article describes current knowledge regarding inflammation-induced neuroplasticity along key elements of enteric neural circuits, what is known about the causes of these changes, and possible therapeutic targets for protecting and/or repairing the integrity of intrinsic enteric neurotransmission. Changes that have been detected in response to inflammation include increased epithelial serotonin availability, hyperexcitability of intrinsic primary afferent neurons, facilitation of synaptic activity amongst enteric neurons, and attenuated purinergic neuromuscular transmission. Dysfunctional propulsive motility has been detected in models of colitis, where causes include the changes described above, and in models of multiple sclerosis and other autoimmune conditions, where autoantibodies are thought to mediate dysmotility. Other cells implicated in inflammation-induced neuroplasticity include muscularis macrophages and enteric glia. Targeted treatments that are discussed include 5-HT4 agonists, cyclooxygenase inhibitors, antioxidants, B cell depletion therapy, and activation of anti-inflammatory pathways.
View details for DOI 10.1152/ajpgi.00206.2019
View details for PubMedID 31604034
Age-Related Changes inGut Microbiota AlterPhenotype of Muscularis Macrophages and Disrupt Gastrointestinal Motility.
Cellular and molecular gastroenterology and hepatology
2019; 7 (1): 243
View details for PubMedID 30585161
- Age-Related Changes in Gut Microbiota Alter Phenotype of Muscularis Macrophages and Disrupt Gastrointestinal Motility CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY 2019; 7 (1): 243-+