Abstract
ObjectiveA growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions play an important role in human health and disease, including hedonic food intake and obesity. We performed a tripartite network analysis based on graph theory to test the hypothesis that microbiota-derived fecal metabolites are associated with connectivity of key regions of the brain’s extended reward network and clinical measures related to obesity.MethodsDTI and resting state fMRI imaging was obtained from 63 healthy subjects with and without elevated body mass index (BMI) (29 males and 34 females). Subjects submitted fecal samples, completed questionnaires to assess anxiety and food addiction, and BMI was recorded.ResultsThe study results demonstrate associations between fecal microbiota-derived indole metabolites (indole, indoleacetic acid, and skatole) with measures of functional and anatomical connectivity of the amygdala, nucleus accumbens, and anterior insula, in addition to BMI, food addiction scores (YFAS) and anxiety symptom scores (HAD Anxiety).ConclusionsThe findings support the hypothesis that gut microbiota-derived indole metabolites may influence hedonic food intake and obesity by acting on the extended reward network, specifically the amygdala-nucleus accumbens circuit and the amygdala-anterior insula circuit. These cross sectional, data-driven results provide valuable information for future mechanistic studies.
Highlights
A growing body of preclinical literature has demonstrated bidirectional signaling between the gut microbiome and the brain, mediated via neural, metabolic, endocrine, and immunerelated signaling mechanisms [1, 2]
The study results demonstrate associations between fecal microbiota-derived indole metabolites with measures of functional and anatomical connectivity of the amygdala, nucleus accumbens, and anterior insula, in addition to body mass index (BMI), food addiction scores (YFAS) and anxiety symptom scores (HAD Anxiety)
Brain networks involving the nucleus accumbens (NAcc), amygdala and the anterior insula are among the most extensively studied brain regions with respect to gut-brain signaling involved in the regulation of non-homeostatic food intake [10]
Summary
A growing body of preclinical literature has demonstrated bidirectional signaling between the gut microbiome and the brain, mediated via neural, metabolic, endocrine, and immunerelated signaling mechanisms [1, 2]. As the composition of the human gut microbiome is dependent on host diet, there is likely strong selective pressure on the microbiota to modulate food intake and eating habits [3] In support of this concept are studies on animal models of obesity that demonstrate the gut microbiota’s influence on ingestive behavior [3, 4]. Brain networks involving the nucleus accumbens (NAcc), amygdala and the anterior insula (aINS) are among the most extensively studied brain regions with respect to gut-brain signaling involved in the regulation of non-homeostatic food intake [10] These regions have been shown to play a role in assessing the hedonic value of food [11]. The aINS plays a role in the experience of emotional feelings and conscious urgings and cravings, in addition to its role as an association cortex, integrating input from subcortical, limbic and executive control brain networks [15, 16]
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