Snehal N. Chaudhari

Assistant Professor, Department of Biochemistry Lab Website snchaudhari@wisc.edu(608) 263-0612

441B HF DeLuca Biochemistry Laboratories
433 Babcock Drive
Madison, WI 53706-1544

Education

B.Tech., Dr. D. Y. Patil University, Mumbai, India
M.S., Pennsylvania State University, University Park, PA
Ph.D., University of Georgia, Athens, GA
Postdoctoral, Harvard Medical School, Boston, MA

Interactions of the gut microbiome with the host; intestinal metabolism in health and disease

Nature chemical biology cover Oct 2021
C. scindens, a commensal gut bacterium (in pink) on a human intestinal epithelial cell.
Chaudhari et. al. 2020

Multi-omic analyses in rodent models and human patients of metabolic syndrome have revealed several parameters associated with disease. These include alterations in metabolites, microbial enzymes, and host transcriptional networks, all of which together contribute to progression of disease phenotypes. However, factors that cause disease continue to remain evasive. Intestinal dysfunction is a hallmark of metabolic syndrome and its associated comorbidities including obesity, inflammatory bowel disease (IBD), and colorectal cancer. Many studies have linked changes in the microbiome to disruption of gut epithelial integrity, which results in metabolic endotoxemia and organismal inflammation. Fecal transplant experiments have substantiated a causal relationship between microbiome and metabolic disease onset. Metabolites synthesized or modified by gut bacteria represent one of the most dominant ways the microbiome influences the host. The Chaudhari lab will study products abundantly present in the gut that are substantially synthesized and modulated by gut bacteria, and how they influence health and disease.

Scanning electron microscope image of himan microvilli
Microvilli on an in vitro differentiated human intestinal epithelial cell as seen under a scanning electron microscope.
Chaudhari et. al. 2021

Approach – The gut epithelial monolayer forms a biochemical and physical barrier that prevents par-enteral organs from being exposed to intestinal luminal contents. Thus, the intestinal epithelium forms the first line of defense against dietary factors that can affect metabolic disease. Despite its importance, the mechanism of how the microbiome induces gut permeability in metabolic diseases remains largely unstudied. Using high-res LC-MS-MS to detect and quantify unique gut metabolites, followed by testing them in physiologically relevant cell biological assays, the Chaudhari lab will study how microbial molecules influence metabolic diseases of the gut, and other organs such as the pancreas, liver, heart, and brain. Using culturomic approaches, individual bacterial strains responsible for production of metabolites will be identified and genetically tested in in vivo models. Studying how gut bacteria influence active metabolites and their mechanism of action in the host will elucidate how the microbiome influences gut health and disease and allow us to mine the biochemical output of the microbiome to identify pharmacological therapeutics.

Photo of SN Chaudhari

Areas of Expertise

  • Cell Structure & Signaling
  • Chemical Biology & Enzymology
  • Metabolism & Endocrinology