The focus of the research in the Henderson Lab is to understand the underlying mechanisms of stress-induced gastrointestinal (GI) dysfunction, specifically the Brain-Gut-Microbiota Axis response to chronic stress. Our primary objectives are to develop novel methods to phenotype patients’ symptoms with stress-induced GI dysfunction, and to identify clinical biomarkers that in turn lead to targeted personalized treatments for the improvement of patients’ symptoms.  Our research includes clinical protocols as well as laboratory approaches to identify translational applications that may be directly implemented to improve patient health outcomes.

The personalized health approach offers a novel perspective of how chronic stress affects intestinal health and disease progression across the lifespan and on how it has significant effects on gut-honed disease states from irritable bowel syndrome, HIV, liver disease, obesity, to rare genetic disorders. How chronic stress ignites a cascade of events, including immune activation of quiescent pathogens and direct detection of pathogens, is an area of active investigation and future continued discovery.

There are two primary ongoing lines of inquiry guides by the NIH Symptom Science Model. Brain-Gut-Microbiota Axis and Chronic Stress Effects on Intestinal Health and Point-of-Use Tool Development to Improve GI Symptom Phenotyping. First the symptom experience is carefully phenotyped through both subjective and objective measures. Next, associated clinically relevant biomarkers are identified.  Lastly, targeted treatments based on the complex phenotype and biomarker evidence are tested and implemented to reduce symptom burden. The combination of these seminal components in novel study design and application of state-of-the-art technologies allows for ability to address critical gaps in the foundational understanding of not only the etiology of symptoms, but also early identification and potential prevention of life long debilitating symptoms (Figure 1).

 

Point-of-Use Tool Development to Improve GI Symptom Phenotyping 

1. Gastrointestinal Pain Pointer

Abdominal pain is a chronic condition experienced by approximately 20% of individuals in the United States. Pain is a public health challenge with both health consequences and the need for improved assessment. To advance the field of pain assessment we developed the Gastrointestinal Pain Pointer (Figure 2).

The aim of the study is to assess the validity and reliability of the Gastrointestinal Pain Pointer (GIPP) as a subjective and objective measure of GI symptoms.

2. Brain-Gut Test Solution

Abnormal GI permeability has been linked with stress-induced GI symptoms. High Resolution Liquid Chromatography- Mass Spectrometry (LC-MS) is used to accurately and precisely measure the concentration of the sugar probes in the urine sample allowing for individual quantification. To develop and test a minimally invasive measure of GI permeability. The Brain-Gut Test Solution; multi-sugar probes includes: lactulose, mannitol, sucrose, and sucralose (Figure 3).

3. Stool Tool

To develop and optimize a multiplexed detection of a minimum of GI pathogen targets that cause gastrointestinal symptoms. To demonstrate the feasibility of developing a paper strip microfluidic device for pathogen detection (Figure 4).

Note: Wendy A. Henderson is a named inventor on all of the above.