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 4 weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27 days 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.

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

“…Consistent with prior reports 23, 26–28 , our data showed that upon introduction of a high ED diet, rats significantly increased their caloric intake compared to when fed a low ED diet. However, by the second week of high ED diet consumption the animals had adjusted their caloric intake.…”

“…High ED diet consumption induced dynamic fluctuations in the gut microbiota. Consistent with prior reports from our laboratory 26 , bacterial diversity was significantly decreased within one week of introducing the high ED diet. This immediate response was ephemeral, similar to the transient increase in caloric intake observed during the first week of high ED diet consumption, as we did not detect statistically significant differences in bacterial diversity after four, eight, and 26 weeks of high ED diet consumption.…”

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

“…The metabolic changes of obesity may be accompanied by altered gastrointestinal microbiota [12–14] and fecal excretion of differing bile acids [15]. Furthermore, weight loss by medical [16] or surgical means [17] profoundly affects bile acid homeostasis as well as fecal microbiota and short chain fatty acid composition.…”

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

“…These data are shedding some eagerly awaited light on the mechanisms of leptin resistance, and can provide an explanation for the imbalance in energy intake and energy expenditure coinciding with gut inflammation as observed in mice [29]. Accordingly, a recent study reported that diet-induced dysbiosis increased gut inflammation and altered vagal gut-brain communication in rats, along with an increase in body fat accumulation [98]. Reversely, a gut microbiota fed a healthy diet produces substances that influence and satiety in a positive manner.…”