title: Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.
abstract: Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation.
authors.affiliation: Department of Veterinary Biosciences & Diagnostic Imaging, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, United States.
authors.forename: Tanusree
authors.initials: T
authors.lastname: Sen
authors.affiliation: Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, GA 30602, United States.
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Cawthon
authors.affiliation: Department of Veterinary Biosciences & Diagnostic Imaging, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, United States.
authors.forename: Benjamin Thomas
authors.initials: BT
authors.lastname: Ihde
authors.affiliation: The Pennsylvania State University, College of Medicine, Neural and Behavioral Sciences, Hershey, PA 17033, United States.
authors.forename: Andras
authors.initials: A
authors.lastname: Hajnal
authors.affiliation: Binghamton University, Psychology, Binghamton, NY 13902, United States.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: DiLorenzo
authors.affiliation: Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, GA 30602, United States. Electronic address: cdlserre@uga.edu.
authors.forename: Claire B
authors.initials: CB
authors.lastname: de La Serre
authors.affiliation: Department of Veterinary Biosciences & Diagnostic Imaging, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, United States. Electronic address: czajak@uga.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czaja
mesh_terms: D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000139:chemically induced*; D004435:Eating; D002149:Energy Intake / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D064307:Microbiota / Q000187:drug effects*; D008840:Microfilament Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors; D053675:Versicans
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D016207:Cytokines; D006023:Glycoproteins; D037102:Lectins; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D012336:RNA, Ribosomal, 16S; C508324:Vcan protein, rat; D053675:Versicans
keywords: Body fat; Inflammation; Microbiota; Obesity; Sugar; Vagal nerve