Background & Aims 5-HT3 receptor (5-HT3R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism (SNP) in HTR3A, c.-42C>T;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this SNP on amygdala reactivity to emotional faces and non-emotional stimuli in female patients with IBS and controls. Methods We measured brain responses during an affect-matching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42C>T genotype (C/C vs. T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT3R. Results The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and non-emotional conditions. Among patients with IBS, the C/C genotype was associated with greater symptom ratings; a subset of IBS patients with the C/C genotype had increased amygdala responses to non-emotional stimuli, compared to other subjects with C/C genotype. Conclusions Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared to T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and non-emotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.

Objective Weight-loss surgery results in significant changes in the anatomy, function and intraluminal environment of the gastrointestinal tract affecting the gut microbiome. While bariatric surgery results in sustained weight loss, decreased appetite and hedonic eating; it is unknown if the surgery-induced alterations in gut microbiota play a role in the observed changes in hedonic eating. We explored the following hypotheses 1) Laparoscopic sleeve gastrectomy results in changes in gut microbial composition ; 2) Alterations in gut microbiota are related to weight loss; 3) Alterations in gut microbiome are associated with changes in appetite and hedonic eating. Methods Eight obese women underwent LSG. Their BMI, body fat mass, food intake, hunger, hedonic eating scores, and stool samples were obtained at baseline and 1-month post-surgery. 16S ribosomal RNA gene sequencing was performed on stool samples. DESeq2 for changes in microbial abundance. Multilevel-sparse partial least squares discriminant analysis was applied to genus level abundance for discriminative microbial signatures. Results LSG resulted in significant reductions in BMI, food intake and hedonic eating. A microbial signature comprised of 5 bacterial genera discriminated between pre and post-surgery status. Several bacterial genera were significantly associated with weight loss (Bilophila (q=3E-05), Faecalibacterium (q=4E-05)), lower appetite (Enterococcus, q=3E-05) and reduced hedonic eating (Akkermansia, q=0.037) after surgery. Conclusions In this preliminary analysis, changes in gut microbial abundance discriminated between pre and postoperative status. Alterations in gut microbiome were significantly associated with weight loss and with reduced hedonic eating after surgery, however a larger sample is needed to confirm these findings.

Background/Aims Greater responsiveness of emotional arousal circuits in relation to delivered visceral pain has been implicated as underlying central pain amplification in Irritable Bowel Syndrome (IBS), with females showing greater responses than males. Methods Functional MRI was used to measure neural responses to an emotion recognition paradigm, using faces expressing negative emotions (fear and anger). Sex and disease differences in the connectivity of affective and modulatory cortical circuits were studied in 47 IBS (27 premenopausal females) and 67 healthy controls (HCs; 38 premenopausal females). Results Male subjects (IBS+HCs) showed greater overall brain responses to stimuli than female subjects in prefrontal cortex, insula, and amygdala. Effective connectivity analyses identified major sex and disease related differences in the functioning of brain networks related to prefrontal regions, cingulate, insula, and amygdala. Males had stronger connectivity between anterior cingulate subregions, amygdala, and insula, whereas females had stronger connectivity to and from the prefrontal modulatory regions (medial/dorsolateral cortex). Conclusions Male IBS demonstrate greater engagement of cortical and affect related brain circuitry compared to male controls and females, when viewing faces depicting emotions previously shown to elicit greater behavioral and brain responses in male subjects.

Background/Objectives:Neuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/Methods:Fifty healthy, premenopausal women, 19 overweight and obese (high BMI=26–38 kg m−2) and 31 lean (BMI=19–25 kg m−2) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.Results:GMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.Conclusions:Overweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors.

Background Ingestion of sweet food is driven by central reward circuits and restrained by endocrine and neurocrine satiety signals. The specific influence of sucrose intake on central affective and reward circuitry and alterations of these mechanisms in the obese are incompletely understood. For this, we hypothesized that (i) similar brain regions are engaged by the stimulation of sweet taste receptors by sucrose and by non-nutrient sweeteners and (ii) during visual food-related cues, obese subjects show greater brain responses to sucrose compared with lean controls. Methods In a double-blind, crossover design, 10 obese and 10 lean healthy females received a sucrose or a non-nutrient sweetened beverage prior to viewing food or neutral images. BOLD signal was measured using a 1.5 Tesla MRI scanner. Key Results Viewing food images after ingestion of either drink was associated with engagement of similar brain regions (amygdala, hippocampus, thalamus, anterior insula). Obese differed from lean subjects in behavioral and brain responses rating both beverages as less tasteful and satisfying, yet demonstrating greater brain responses. Obese subjects also showed engagement of an additional brain network (including anterior insula, anterior cingulate, hippocampus, and amygdala) only after sucrose ingestion. Conclusions & Inferences Obese subjects had a reduced behavioral hedonic response, yet a greater engagement of affective brain networks, particularly after sucrose ingestion, suggesting that in obese subjects, lingual and gut-derived signaling generate less central hedonic effects than food-related memories in response to visual cues, analogous to response patterns implicated in food addiction.