title: Energy-dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation.
abstract: Obesity is associated with consumption of energy-dense diets and development of systemic inflammation. Gut microbiota play a role in energy harvest and inflammation and can influence the change from lean to obese phenotypes. The nucleus of the solitary tract (NTS) is a brain target for gastrointestinal signals modulating satiety and alterations in gut-brain vagal pathway may promote overeating and obesity. Therefore, we tested the hypothesis that high-fat diet‑induced changes in gut microbiota alter vagal gut-brain communication associated with increased body fat accumulation. Sprague-Dawley rats consumed a low energy‑dense rodent diet (LFD; 3.1 kcal/g) or high energy‑dense diet (HFD, 5.24 kcal/g). Minocycline was used to manipulate gut microbiota composition. 16S Sequencing was used to determine microbiota composition. Immunofluorescence against IB4 and Iba1 was used to determine NTS reorganization and microglia activation. Nodose ganglia from LFD rats were isolated and co-cultured with different bacteria strains to determine neurotoxicity. HFD altered gut microbiota with increases in Firmicutes/Bacteriodetes ratio and in pro-inflammatory Proteobacteria proliferation. HFD triggered reorganization of vagal afferents and microglia activation in the NTS, associated with weight gain. Minocycline-treated HFD rats exhibited microbiota profile comparable to LFD animals. Minocycline suppressed HFD‑induced reorganization of vagal afferents and microglia activation in the NTS, and reduced body fat accumulation. Proteobacteria isolated from cecum of HFD rats were toxic to vagal afferent neurons in culture. Our findings show that diet‑induced shift in gut microbiome may disrupt vagal gut‑brain communication resulting in microglia activation and increased body fat accumulation.
authors.affiliation: Washington State University, Integrative Physiology and Neuroscience, Pullman, WA, USA.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Vaughn
authors.affiliation: Washington State University, Integrative Physiology and Neuroscience, Pullman, WA, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Cooper
authors.affiliation: Binghamton University, Psychology, Binghamton, NY, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: DiLorenzo
authors.affiliation: Washington State University, School of Molecular Biosciences, Pullman, WA, USA.
authors.forename: Levi J
authors.initials: LJ
authors.lastname: O'Loughlin
authors.affiliation: Washington State University, School of Molecular Biosciences, Pullman, WA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Konkel
authors.affiliation: Washington State University, Integrative Physiology and Neuroscience, Pullman, WA, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Peters
authors.affiliation: The Pennsylvania State University, College of Medicine, Neural and Behavioral Sciences, Hershey, PA, USA.
authors.forename: Andras
authors.initials: A
authors.lastname: Hajnal
authors.affiliation: University of Georgia, Veterinary Biosciences and Diagnostic Imaging, Athens, GA, USA.
authors.forename: Tanusree
authors.initials: T
authors.lastname: Sen
authors.affiliation: University of Georgia, Foods and Nutrition, Athens, GA, USA.
authors.forename: Sun Hye
authors.initials: SH
authors.lastname: Lee
authors.affiliation: University of Georgia, Foods and Nutrition, Athens, GA, USA, cdlserre@uga.edu.
authors.forename: Claire B
authors.initials: CB
authors.lastname: de La Serre
authors.affiliation: University of Georgia, Veterinary Biosciences and Diagnostic Imaging, Athens, GA, USA, czajak@uga.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czaja
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D009620:Nodose Ganglion / Q000378:metabolism / Q000382:microbiology; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D037102:Lectins; D008070:Lipopolysaccharides; D012336:RNA, Ribosomal, 16S; D008911:Minocycline