Malú Gámez Tansey
Professor/Co-Director
University of Florida
Malú Gámez Tansey is the Co-Director of the Center for Translational Research in Neurodegenerative Disease and the Normal and Susan Fixel Chair in Neuroscience and Neurology at the University of Florida. BS/MS in Biological Science, Stanford; PhD in Cell Regulation, UTSouthwestern; postdoc at Washington University with Eugene M. Johnson, Jr. In 2001, joined a private biotech as Chemical Genetics group leader at Xencor Inc and co-invented soluble TNF inhibitors which she subsequently used as tools as Assistant Professor at UTSW in 2002 to investigate the role of neuroinflammation in neurodegenerative disease and which have now been advanced to clinical trials in Alzheimer's disease and COVID19 for cytokine storm. In 2009, she moved to Emory University as tenured Professor of Physiology where she established the Center for Neurodysfunction and Inflammation. She is a fierce advocate for women and other under-represented groups in STEM and has earned several mentoring awards from students and peers for her efforts in this area. Today, her lab focuses on the role of inflammation and immune system responses in brain health and development of disease with a long-term goal of developing better therapies to prevent and/or delay these diseases.
abstract
Functional and Dysfunctional Relationships between Gut Barrier and Microbiota, Plasma Inflammatory Markers, and Clinical Features: Lessons from Sporadic Parkinson’s Disease
Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. We sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.
Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.
We found that calprotectin was increased and SCFAs were decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Importantly, intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, but are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex dependent. Our findings reveal potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.