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.

Six‐Week High‐Fat Diet Alters the Gut Microbiome and Promotes Cecal Inflammation, Endotoxin Production, and Simple Steatosis without Obesity in Male Rats

“…The present study revealed that 6 weeks of HFD feeding increased the abundance of Firmicutes , Clostridiales , Proteobacteria , and Streptococcaceae , which may be influenced by consumption of energy dense diets. These data are consistent with prior research demonstrating that a short‐term (7‐day) HFD increased different subclasses of Firmicutes such as Erysipelotrichale (Vaughn et al, ), which was consistent with findings from the present study. Likewise, a prior study of female mice fed a western diet high in carbohydrates and saturated fat for 14 days resulted in increased abundance of Firmicutes (Yin et al, ).…”

Human Gut Microbiota: Toward an Ecology of Disease

“…During studies on the causative factors of obesity it was observed that the GI microbiota may modulate expression of taste receptors (Miras and le Roux, 2013; Avau et al, 2015; Avau and Depoortere, 2015; Murtaza et al, 2017), affect the vagus nerve which controls the gut-brain axis (Rhee et al, 2009; Bercik et al, 2012; Collins et al, 2012; Vaughn et al, 2017) and influence the release of toxins and neuro-transmitters (Kollai et al, 1994; Lyte et al, 2011; Clarke et al, 2014). In a small human study, probiotics were found to stimulate both number and diversity of gut microbiota in obese adults and reduced host cravings, raising the untested possibility that the subjects' eating preferences may have been modified (Kadooka et al, 2010).…”

Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats

“…Vagal afferents carry information from the gut to the NTS. Reports from our laboratory and others have shown that consumption of a high ED diet triggers microglia activation in the nodose glanglia, NTS, and hypothalamus 27, 52, 53 . Results from this study showed that high ED diet consumption induced an inflammatory response reflected by microglia activation in the intermediate NTS after four weeks.…”