Gut microbiota induces weight gain and inflammation in the gut and adipose tissue independent of manipulations in diet, genetics, and immune development
Devesha H. Kulkarni,
Brigida Rusconi,
Alexandria N. Floyd,
Elisabeth L. Joyce,
Khushi B. Talati,
Hrishi Kousik,
Dereck Alleyne,
Dalia L. Harris,
Lorena Garnica,
Ryan McDonough,
Shay S. Bidani,
Hrishikesh S. Kulkarni,
Elizabeth P. Newberry,
Keely G. McDonald,
Rodney D. Newberry
Affiliations
Devesha H. Kulkarni
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Brigida Rusconi
Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Alexandria N. Floyd
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Elisabeth L. Joyce
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Khushi B. Talati
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Hrishi Kousik
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Dereck Alleyne
Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Dalia L. Harris
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Lorena Garnica
Division of Pulmonary and Critical Care Medicine, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Ryan McDonough
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Shay S. Bidani
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Hrishikesh S. Kulkarni
Division of Pulmonary and Critical Care Medicine, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Elizabeth P. Newberry
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Keely G. McDonald
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
Rodney D. Newberry
Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA
ABSTRACTObesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, and gut microbes. Animal studies have identified roles for each of these, however the contribution(s) specifically attributed to the gut microbiota remain unclear, as studies have used combinations of genetically altered mice, high fat diet, and/or colonization of germ-free mice, which have an underdeveloped immune system. We investigated the role(s) of the gut microbiota driving obesity and inflammation independent of manipulations in diet and genetics in mice with fully developed immune systems. We demonstrate that the human obese gut microbiota alone was sufficient to drive weight gain, systemic, adipose tissue, and intestinal inflammation, but did not promote intestinal barrier leak. The obese microbiota induced gene expression promoting caloric uptake/harvest but was less effective at inducing genes associated with mucosal immune responses. Thus, the obese gut microbiota is sufficient to induce weight gain and inflammation.