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Sclocco R, Fisher H, Staley R, Han K, Mendez A, Bolender A, Coll-Font J, Kettner NW, Nguyen C, Kuo B, Napadow V. Cine gastric MRI reveals altered Gut-Brain Axis in Functional Dyspepsia: gastric motility is linked with brainstem-cortical fMRI connectivity. Neurogastroenterol Motil 2022; 34:e14396. [PMID: 35560690 PMCID: PMC9529794 DOI: 10.1111/nmo.14396] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/31/2022] [Accepted: 04/25/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Functional dyspepsia (FD) is a disorder of gut-brain interaction, and its putative pathophysiology involves dysregulation of gastric motility and central processing of gastric afference. The vagus nerve modulates gastric peristalsis and carries afferent sensory information to brainstem nuclei, specifically the nucleus tractus solitarii (NTS). Here, we combine MRI assessment of gastric kinematics with measures of NTS functional connectivity to the brain in patients with FD and healthy controls (HC), in order to elucidate how gut-brain axis communication is associated with FD pathophysiology. METHODS Functional dyspepsia and HC subjects experienced serial gastric MRI and brain fMRI following ingestion of a food-based contrast meal. Gastric function indices estimated from 4D cine MRI data were compared between FD and HC groups using repeated measure ANOVA models, controlling for ingested volume. Brain connectivity of the NTS was contrasted between groups and associated with gastric function indices. KEY RESULTS Propagation velocity of antral peristalsis was significantly lower in FD compared to HC. The brain network defined by NTS connectivity loaded most strongly onto the Default Mode Network, and more strongly onto the Frontoparietal Network in FD. FD also demonstrated higher NTS connectivity to insula, anterior cingulate and prefrontal cortices, and pre-supplementary motor area. NTS connectivity was linked to propagation velocity in HC, but not FD, whereas peristalsis frequency was linked with NTS connectivity in patients with FD. CONCLUSIONS & INFERENCES Our multi-modal MRI approach revealed lower peristaltic propagation velocity linked to altered brainstem-cortical functional connectivity in patients suffering from FD suggesting specific plasticity in gut-brain communication.
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Affiliation(s)
- Roberta Sclocco
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
- Department of Radiology, Logan University, Chesterfield, MO, USA
| | - Harrison Fisher
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
| | - Rowan Staley
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
- Department of Gastroenterology and Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kyungsun Han
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
- Korean Institute of Oriental Medicine, Daejeon, Korea
| | - April Mendez
- Department of Gastroenterology and Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Andrew Bolender
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
- Department of Gastroenterology and Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jaume Coll-Font
- Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA
| | | | - Christopher Nguyen
- Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA
- Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Braden Kuo
- Department of Gastroenterology and Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Vitaly Napadow
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Radiology, Harvard Medical School, Charlestown, MA, USA
- Department of Radiology, Logan University, Chesterfield, MO, USA
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Wang X, Zhang S, Pasricha PJ, Chen JDZ. Ameliorating effects of sacral neuromodulation on gastric and small intestinal dysmotility mediated via a sacral afferent-vagal efferent pathway. Neurogastroenterol Motil 2020; 32:e13837. [PMID: 32189439 DOI: 10.1111/nmo.13837] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 02/04/2020] [Accepted: 02/18/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIMS In a recent study of sacral nerve stimulation (SNS) for colonic inflammation, a possible spinal-vagal pathway was implicated. The aim of this study was to provide evidence for such a pathway by investigating the effects of SNS on dysmotility of the stomach and duodenum that are not directly innervated by the sacral efferents. METHODS Twenty-seven rats were chronically implanted with wire electrodes for SNS and gastrointestinal slow waves. SNS was performed in several acute sessions to investigate its effects on gastric/duodenal slow waves and emptying/transit impaired by glucagon and rectal distention (RD). RESULTS (a) SNS increased the percentage of normal gastric slow waves impaired by glucagon (from 53.9% to 77.0%, P < .0001) and RD (from 64% to 78%, P = .037). This improvement was abolished by atropine. (b) Similar effects were observed with SNS on duodenal slow waves, which was also blocked by atropine. (c) SNS normalized delayed gastric emptying induced by glucagon (control: 61.3%, glucagon: 44.3%, glucagon + SNS: 65.8%) and RD (control: 61.3%, RD: 46.7%, RD + SNS: 64.3%). It also normalized small intestinal transit delayed by RD (P = .001, RD + SNS vs RD; P = .9, RD + SNS vs control). (4) Both glucagon and RD induced an increase in the sympathovagal ratio (P = .007, glucagon vs baseline; P < .001, RD vs baseline) and SNS decreased the ratio (P = .006, glucagon + SNS vs glucagon; P = .04, RD + SNS vs RD). CONCLUSIONS Neuromodulation of the sacral nerve improves gastric and small intestinal pacemaking activity and transit impaired by glucagon and RD by normalizing the sympathovagal balance via a retrograde neural pathway from the sacral nerve to vagal efferents.
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Affiliation(s)
- Ximeng Wang
- Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shengai Zhang
- Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Pankaj J Pasricha
- Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jiande D Z Chen
- Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Kim BJ, Kuo B. Gastroparesis and Functional Dyspepsia: A Blurring Distinction of Pathophysiology and Treatment. J Neurogastroenterol Motil 2019; 25:27-35. [PMID: 30509017 PMCID: PMC6326193 DOI: 10.5056/jnm18162] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 10/26/2018] [Accepted: 10/30/2018] [Indexed: 12/13/2022] Open
Abstract
Gastroparesis and functional dyspepsia are 2 of the most common gastric neuromuscular disorders. These disorders are usually confused, having both similarities and differences. The pathophysiology of these disorders involves abnormal gastric motility, visceral hypersensitivity, mucosal inflammation, and various cellular changes. Both disorders have similar symptoms such as epigastric pain or discomfort, early satiety, and bloating. If patients suspected of having either gastroparesis or functional dyspepsia present with upper gastrointestinal symptoms, they should undergo upper endoscopy to exclude an alternative organic cause. Although the gastric emptying rate is frequently assessed during the clinical workup of patients with gastroparesis or functional dyspepsia, the correlation between gastric emptying and the symptoms is generally poor. Once the diagnosis of gastroparesis or functional dyspepsia is made, treatment should focus on the predominant symptom. Recently, various treatment modalities have been developed and validated. Prokinetic agents are generally used as treatment for both gastroparesis and functional dyspepsia. Acid-suppressive therapy, Helicobacter pylori eradication, and use of drugs that enhance gastric accommodation are employed for functional dyspepsia. Psychoactive drugs are also effective in symptom control. For gastroparesis, antiemetic agents, ghrelin receptor agonists, and serotonergic agents are used aside from prokinetic agents. Acupuncture and gastric electrical stimulation can be attempted. In severe cases, endoscopic and surgical interventions are considered for symptom control.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.,Gastrointestinal Unit, Center of Neuroenteric Health, Massachusetts General Hospital, Harvard Medical School, Boston, USA
| | - Braden Kuo
- Gastrointestinal Unit, Center of Neuroenteric Health, Massachusetts General Hospital, Harvard Medical School, Boston, USA
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Zhang CL, Geng CH, Yang ZW, Li YL, Tong LQ, Gao P, Gao YQ. Changes in patients’ symptoms and gastric emptying after Helicobacter pylori treatment. World J Gastroenterol 2016; 22:4585-4593. [PMID: 27182168 PMCID: PMC4858640 DOI: 10.3748/wjg.v22.i18.4585] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 02/29/2016] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients.
METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups.
RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05).
CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.
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Zhou W, Su J, Zhang H. Efficacy and Safety of Acupuncture for the Treatment of Functional Dyspepsia: Meta-Analysis. J Altern Complement Med 2016; 22:380-9. [PMID: 27028618 DOI: 10.1089/acm.2014.0400] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES Functional dyspepsia (FD) is a common gastrointestinal disorder. Currently, no established optimal treatment is available. The aim of this study was to assess the efficacy of acupuncture in relieving symptoms and improving quality of life in patients with FD. METHODS PubMed, MEDLINE, Web of Science, Sino-Med, China National Knowledge Infrastructure, VIP databases, and Google Scholar engine were searched from inception through April 2014 to identify randomized controlled trials of acupuncture therapy that reported on overall FD symptoms or FD-related quality of life as a primary outcome. The Cochrane Collaboration's risk of bias tool, RevMan 5.0, and Stata 12.0 software were used for meta-analysis. Data were pooled to calculate relative risk (RRs) and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data using random-effects models. RESULTS Twenty-four English- and Chinese-language articles describing randomized, placebo-controlled, clinical trials involving 3097 patients were included. Acupuncture significantly improved FD symptoms in studies reporting outcomes using dichotomous (RR, 1.19; 95% CI, 1.12-1.27; p < 0.001) and continuous (standardized MD [SMD], -0.78; 95% CI, -1.21 to -0.35; p = 0.0004) variables. Pooled analyses showed that acupuncture improved FD-related (weighted MD [WMD], 5.97; 95% CI, 3.14-8.80; p = 0.0002) and health-related (WMD, 6.83; 95% CI, 3.02-10.65; p = 0.004) quality of life, without serious adverse events. However, acupuncture failed to increase plasma motilin concentration (SMD, 0.67; 95% CI, -0.07 to 1.42; p = 0.08). CONCLUSIONS Acupuncture appears to be efficacious in relieving FD symptoms and improving quality of life.
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Affiliation(s)
- Weimei Zhou
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University , Nanjing, China
| | - Jiewen Su
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University , Nanjing, China
| | - Hongjie Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University , Nanjing, China
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