MicroRNAs… MicroRNAs… gut MicroRNAs.

Praveen Sethupathy, Ph.D.
Assistant Professor of Genetics
UNC-Chapel Hill

Dr. Praveen Sethupathy studies microRNAs and how they respond to gut microbes.

Here is a short recap from his talk:

  • Non-coding RNA encompasses a large class of RNA, including microRNA. The Sethupathy lab in interested in how miRNA regulate diseases, can act as biomarkers of disease, and how they respond to changes in environment. 
  • Sethupathy lab has studied how miRNA is related to Diabetes and Obesity, but recent RNA sequencing data has turned their attention to miRNA in the GI system and their  relationship to Microbiota 
  • Their hypothesis is that miRNA respond to the microbiota, this response is cell-type specific and that miRNA can control Enteroendocrine cells
  • They have mapped miRNA in intestinal epithelial cells and have seen that in GI stem cells, there is increased miR-30d, miR-92, miR-7, miR-375, and let-7, while miRNA-375 is increased in microbiota-sensitive stem cells
    • An ex vivo knockout of miR-375 using LNA 375 led to proliferation of EECs
  • In conclusion, miRNA are specific to cell types in the GI epithelium, miRNA are more sensitive in stem cells than in other GI cells, and a sub-population analysis of miRNA is needed to check response to microbiota. 
You can see more of Dr. Sethupathy’s work at www.med.unc.edu/genetics/sethupathylab.

Window to the gut… literally

Xiling Shen, Ph.D.
Associate Professor of Biomedical Engineering
Duke University

Dr. Shen’s laboratory recently moved from Cornell University and has developed a unique 3D printed scaffold to image the gut in awake behaving animals. The device can be used to image from stem cells, to bacteria, to neurons. His team is also working on peripheral nerve stimulation and recording devices for nerves innervating the gut.

This story was highlighted as one of the top 100 stories by Discovery Magazine in 2016

Gut Microbes and Behavior

Ian Carroll, Ph.D.
Assistant Professor of Medicine at UNC-Chapel Hill

Dr. Carroll’s research studies how intestinal microbes influence gut physiology and behaviors. Dr. Carroll also uses high throughput sequencing of bacterial genes to characterize the enteric microbiota in human subjects with gastrointestinal disease and mouse models of intestinal inflammation. His goal is to develop enteric microbial-based therapies for the treatment of gut diseases.

In germ free conditions, mice have enlarged cecums, blunted villi, and less weight gain per calories consumed. These changes reverse after inoculation. Microbiota influences emotional state in a complex fashion and germ free mice have higher stress and lower anxiety. Stress increases or decreases depending on the species of bacteria added. Emotional changes after inoculation of germ free mice are not observed when the vagus is severed.
In starvation states, as seen in anorexia, microbiota diversity decreases and the relative proportions of species change. These changes appear to perpetuate symptoms in anorexia. A single case study showed fecal transplant leading to weight gain in a human subject and such interventions might have therapeutic potential in the future.

Carcinogenic gut microbes

Janelle Arthur, Ph.D.
Assistant Professor of Microbiology and Immunology
UNC-Chapel Hill School of Medicine

Janelle’s group seeks to understand how inflammation alters the pro-carcinogenic capabilities of the microbiota, with the long-term goal of targeting resident microbes as a preventative and therapeutic strategy to lessen inflammation and reduce the risk of colorectal cancer.

They are focus on clinical strains of intestinal E. coli isolated directly from human inflammatory bowel disease (IBD) patients, who are known to experience a high risk of colorectal cancer.  Janelle’s goal is to uncover novel microbial targets will enable us to manipulate the intestinal microbiota as a therapeutic target for human digestive diseases and cancer.

Autism and the gut

Dr. Yong Hui Jiang

Yong-Hui is an Associate Professor of Pediatrics at Duke University. His laboratory  investigates the diseases underlying neurodevelopmental disorders including autism. They focus on genes linked to synapse development and behavioral plasticity. They use molecular and behavioral assays in genetically-modified mice that model human diseases. Although their laboratory does not study the gut directly, 9 in 10 children with Autism suffer from GI complications that may be linked to neurodevelopment disorders of the enteric nervous system.

Gut feelings in anorexia

We have a great talk coming up for our September meeting.

Our friend Gastronaut Dr. Nancy Zucker will be sharing her work on “Visceral hypersensitivity: an emerging concept for individuals with eating disorders”.  Nancy is an Eating Disorders Specialist and , Associate Professor in Psychiatry and Behavioral Sciences at Duke University.

Here is a recent story in The New York Times highlighting Nancy’s work: http://nyti.ms/1KKXk2T