Surgically Induced Changes in Gut Microbiome and Hedonic Eating as Related to Weight Loss: Preliminary Findings in Obese Women Undergoing Bariatric Surgery.

OBJECTIVE: Weight loss surgery results in significant changes in the anatomy, function, and intraluminal environment of the gastrointestinal tract affecting the gut microbiome. Although bariatric surgery results in sustained weight loss, decreased appetite, and hedonic eating, it is unknown whether 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 (LSG) 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 body mass index, body fat mass, food intake, hunger, hedonic eating scores, and stool samples were obtained at baseline and 1-month postsurgery. 16S ribosomal RNA gene sequencing was performed on stool samples. DESeq2 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 body mass index, food intake, and hedonic eating. A microbial signature composed of five bacterial genera discriminated between pre- and postsurgery 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 = .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.

Sex Commonalities and Differences in Obesity-Related Alterations in Intrinsic Brain Activity and Connectivity.

OBJECTIVE: This study aimed to characterize obesity-related sex differences in the intrinsic activity and connectivity of the brain's reward networks. METHODS: Eighty-six women (n = 43) and men (n = 43) completed a 10-minute resting functional magnetic resonance imaging scan. Sex differences and commonalities in BMI-related frequency power distribution and reward seed-based connectivity were investigated by using partial least squares analysis. RESULTS: For whole-brain activity in both men and women, increased BMI was associated with increased slow-5 activity in the left globus pallidus (GP) and substantia nigra. In women only, increased BMI was associated with increased slow-4 activity in the right GP and bilateral putamen. For seed-based connectivity in women, increased BMI was associated with reduced slow-5 connectivity between the left GP and putamen and the emotion and cortical regulation regions, but in men, increased BMI was associated with increased connectivity with the medial frontal cortex. In both men and women, increased BMI was associated with increased slow-4 connectivity between the right GP and bilateral putamen and the emotion regulation and sensorimotor-related regions. CONCLUSIONS: The stronger relationship between increased BMI and decreased connectivity of core reward network components with cortical and emotion regulation regions in women may be related to the greater prevalence of emotional eating. The present findings suggest the importance of personalized treatments for obesity that consider the sex of the affected individual.

The TANTALUS system for obesity: effect on gastric emptying of solids and ghrelin plasma levels.

BACKGROUND: Gastric electrical stimulation (GES), using the implantable TANTALUS System, is being explored as a treatment for obesity. The system delivers nonstimulatory electrical signals synchronized with gastric slow waves, resulting in stronger contractions. We hypothesized that this GES may enhance gastric emptying and as a result affect plasma ghrelin and insulin homeostasis. The aim was to test the effect of GES on gastric emptying of solids and on ghrelin and insulin blood levels in obese subjects. METHODS: The system consists of 3 pairs of gastric electrodes connected to an implantable pulse generator. Gastric emptying test (GE) of solids was performed twice, on separate days, a few weeks after implantation, before and after initiation of stimulation. Blood samples for ghrelin and insulin were taken at baseline and at 15, 30, 60 and 120 min after the test meal. RESULTS: There were 11 females, 1 male, mean age 39.1 +/- 8.9 years, mean BMI 41.6 +/- 3.4. Data is available from 11 subjects; GE was normal in 9 subjects and accelerated in 2 subjects. GES significantly accelerated GE compared to control: percent retention at 2 hours 18.7 +/- 12.2 vs 31.9 +/- 16.4, respectively (P < 0.01). Overall, there was no significant change in ghrelin or insulin profile after food intake. Ghrelin levels fell significantly at 60 min compared to baseline during stimulation (P = 0.014) and control (P = 0.046). CONCLUSION: GES results in a significant acceleration of gastric emptying of solids in obese subjects. GES did not have a significant effect on postprandial ghrelin levels when compared to control.

Patterns of brain structural connectivity differentiate normal weight from overweight subjects.

BACKGROUND: Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. AIM: To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. METHODS: Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. RESULTS: 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network. CONCLUSIONS: 1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity.

The effect of eating on lower esophageal sphincter electrical activity.

Electrical activity of the lower esophageal sphincter (LES) has been recorded mainly in vitro and in anesthetized animals. Swallowing produces relaxation of the LES, followed by its contraction. These changes should be associated with changes in LES electrical activity. To determine whether changes in LES electrical activity can be used to recognize the beginning of a meal, four dogs were implanted with two electrodes in the longitudinal axis of the LES. The electrodes were connected to an implantable device for recording of electrical activity. After recovery, dogs underwent two experiments: 1) combined recordings of LES electrical activity and esophageal manometry to test the effect of dry swallows, water, and solid food swallows on LES electrical activity and 2) telemetric recording of LES electrical activity during a standard meal. All amplitudes were in mV, means+/-SD, ANOVA, P<0.05. In experiment 1, an increase in the amplitude of LES electrical activity was associated with the substance being swallowed, i.e., at rest: 0.31+/-0.06; dry swallows: 0.6+/-.0.1; water: 0.67+/-0.12; solid food: 1.06+/-0.17, P<0.001. In experiment 2, there was a pronounced and characteristic increase in amplitude of LES electrical activity during feeding, 0.26+/-0.1; during fasting, 0.99+/-0.23; while eating, 0.31+/-0.1 postprandial, P<0.001. In conclusion, the beginning and duration of a meal are identified by distinct, easily recognizable changes in the amplitude of LES electrical activity. These changes depend on the type of the substance being swallowed and are most prominent with solid food. Changes in LES electrical activity can potentially be used for automatic eating detection.

Gastric electrical stimulation with the TANTALUS System in obese type 2 diabetes patients: effect on weight and glycemic control.

BACKGROUND: The TANTALUS System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. METHOD: Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. RESULTS: Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7 +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). CONCLUSIONS: Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.

Effect of electrical stimulation of the LES on LES pressure in a canine model.

Gastric electrical stimulation modulates lower esophageal sphincter pressure (LESP). High-frequency neural stimulation (NES) can induce gut smooth muscle contractions. To determine whether lower esophageal sphincter (LES) electrical stimulation (ES) can affect LESP, bipolar electrodes were implanted in the LES of four dogs. Esophageal manometry during sham or ES was performed randomly on separate days. Four stimuli were used: 1) low-frequency: 350-ms pulses at 6 cycles/min; 2) high-frequency-1: 1-ms pulses at 50 Hz; 3) high-frequency-2: 1-ms pulses at 20 Hz; and 4) NES: 20-ms bipolar pulses at 50 Hz. Recordings were obtained postprandially. Tests consisted of three 20-min periods: baseline, stimulation/sham, and poststimulation. The effect of NES was tested under anesthesia and following IV administration of l-NAME and atropine. Area under the curve (AUC) and LESP were compared among the three periods, by ANOVA and t-test, P < 0.05. Data are shown as means +/- SD. We found that low-frequency stimulation caused a sustained increase in LESP: 32.1 +/- 12.9 (prestimulation) vs. 43.2 +/- 18.0 (stimulation) vs. 50.1 +/- 23.8 (poststimulation), P < 0.05. AUC significantly increased during and after stimulation. There were no significant changes with other types of ES. With NES, LESP initially rose and then decreased below baseline (LES relaxation). During NES, N(G)-nitro-l-arginine methyl ester increased both resting LESP and the initial rise in LESP and markedly diminished the relaxation. Atropine lowered resting LESP and abolished the initial rise in LESP. In conclusion, low frequency ES of the LES increases LESP in conscious dogs. NES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.

Association between gastric electromechanical activity and satiation in dogs.

OBJECTIVE: The objective of this study was to validate the use of impedance for measurement of antral contractions and to determine the relationship between food-induced changes in gastric motility and satiation. RESEARCH METHODS AND PROCEDURES: In Experiment 1, three dogs were implanted with an antral strain gauge and bipolar electrodes for measurement of local tissue impedance. Impedance and strain gauge recordings were obtained simultaneously during antral contractions to correlate impedance changes with contractile events. In Experiment 2, seven dogs were implanted with two pairs of gastric electrodes for simultaneous recording of slow wave activity and impedance. The changes in the rate of slow waves and of antral contractions assessed by impedance during food intake were characterized. RESULTS: Variations in strain gauge amplitude were highly correlated with changes in antral impedance (R2: 0.70 to 0.82, p < 0.05). In Experiment 2, slow wave rate was significantly reduced after food intake and reached a nadir at satiation (5.0 +/- 0.3 vs. 3.8 +/- 0.5 events/min, p < 0.001). Likewise, the amplitude of antral contractions assessed by variations in impedance was significantly increased after food intake, peaking at satiation (5.3 +/- 1.4 vs. 12.2 +/- 4.3 Ohms, p < 0.01). DISCUSSION: Measurement of impedance is a reliable tool for assessing gastric contractility. Food ingestion significantly reduces slow wave rate and enhances antral contractions. Peak changes in these two variables occur at the time of satiation. Electrical measurements of both slow waves and impedance may be used to estimate gastric motility and satiation.

Constipation caused by functional outlet obstruction.

Functional constipation is a very common problem in Western societies. Functional outlet obstruction, part of the spectrum of functional constipation, is suspected when patients present with select symptoms. Diagnosis is commonly made with anorectal manometry, electromyography, and rectal evacuation tests. Abnormal test patterns include poor relaxation and contraction of the anal sphincter in response to attempted defecation and difficult rectal evacuation. Several treatment approaches have been tested in these patients. Biofeedback training is considered the most specific therapeutic modality, and it is particularly attractive because of its safety. This review provides an assessment of the diagnostic tests for functional outlet obstruction and summarizes current options for therapy.

Electrical activity from colon overlaps with normal gastric electrical activity in cutaneous recordings.

The stability of EGG recordings is affected by a variety of artifacts. The aim of this study was to investigate possible overlapping of dominant frequencies in recorded cutaneous electrical activity arising simultaneously from the stomach and/or colon. Ten normal volunteers, eight posttotal colectomy patients, and four patients posttotal gastrectomy were studied. Fasting cutaneous recordings were obtained using four pediatric ECG electrodes attached to the abdominal surface. Electrical activity was recorded and digitally analyzed using custom-designed software. Spectral analysis after gastrectomy and colectomy showed persistence of power peaks in the gastric electrical activity range of frequency (2.5-3.75 cpm). In conclusion, noninvasively obtained colonic frequencies overlap EGG. This hypothesis is supported by the persistence of power peaks in the EGG range of frequency after gastrectomy and colectomy. Therefore, we conclude that contribution of electrical activity arising from the colon could substantially affect EGG recordings.

Asociacion entre Infeccion por helicobacter pylori y cancer gastrico en Colombia / Helicobacter pylori and gastric cancer in Colombia

Introducción Existe evidencia en la literatura que apoya la asociación entre la infección por helicobacter pylori (HP) y el cáncer gástrico (CG). Diseñamos un estudio de casos y controles con el propósito de confirmar esta asociación en Colombia uno de los países con más alta incidencia de CG en el mundo e identificar otros factores de riesgo para el desarrollo de esta neoplasia. Conclusiones En Colombia donde un porcentaje alto de la población está infectada por HP, el CG tiene una etiología multifactorial en la que el HP puede estar involucrado pero otros factores genéticos, ambientales y dietéticos parecen ser más importantes en la progresión del proceso de carcinogénesis. Materiales y métodos Un total de 85 pacientes con cáncer gástrico fueron comparados con 170 controles sintomáticos, 85 con gastritis crónica y 85 con endoscopia normal. La infección por HP se determinó usando estudios serológicos, se investigó sobre factores ambientales, familiares y nutricionales usando un formulario de recolección de datos ya validado. Resultados No encontramos diferencias estadísticamente significativas entre los casos y controles en relación con la infección por HP. El antecedente de tabaquismo, consumo de alcohol y un pobre nivel socioeconómico fue más común en los pacientes con CG. El consumo de trigo y nabos constituyen factores de riesgo para el desarrollo de CG, igualmente existen otros alimentos que parecen tener una asociación protectora

Asociacion entre infeccion por Helicobacter pylori y cancer gastrico en Colombia / Gastric cancer and H. Pylori in Colombia

Introducción: existe evidencia en la literatura que apoya la asociación entre la infección por Helicobacter pylori (HP) y el cáncer gástrico (CG). Diseñamos un estudio de casos y controles con el propósito de confirmar esta asociación en Colombia, uno de los países con más alta incidencia de CG en el mundo e identificar otros factores de riesgo para el desarrollo de esta neoplasia. Material y Métodos: se compararon 85 pacientes con cáncer gástrico con 170 controles sintomáticos, 85 con gastritis crónica y 85 con endoscopia normal. La infección por HP se determinó usando estudios serológicos, se investigó sobre factores ambientales, familiares y nutricionales usando un formulario de recolección de datos ya validado. Resultados: no encontramos diferencias estadísticamente significativas entre los casos y los controles en relación con la infección por HP. Los antecedentes de tabaquismo, de consumo de alcohol y un pobre nivel socioeconómico fueron más comunes en los pacientes con CG. El consumo de trigo y nabos constituye un factor de riesgo para el desarrollo de CG, igualmente existen otros alimentos que parecen tener una asociación protectora. Conclusiones: en Colombia donde un porcentaje alto de la población está infectada por HP, el CG tiene una etiología multifactorial en la que el HP puede estar involucrado pero otros factores genéticos, ambientales y dietéticos parecen ser más importantes en la progresión del proceso de carcinogénesis.