Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.

BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.

The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.

Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliable to evaluate prokinetic agents. Male ddY mice were used. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (80 mM) was given 60 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), neostigmine (30 µg/kg), acotiamide (10-100 mg/kg), and daikenchuto (100-1000 mg/kg) were given 40 min before the measurement. AITC impaired gastric motility without mucosal damages, which reverted 24 h after AITC treatment. The decreased motility induced by AITC was restored by prokinetic agents such as itopride, mosapride, neostigmine, and acotiamide. In separate experiment, daikenchuto recovered the decreased motility induced by AITC, although daikenchuto had no effect on motility in normal condition. In conclusion, it is considered that the AITC-induced impaired gastric motility mouse model is useful to develop new prokinetic agents for treatment of FD, and to re-evaluate traditional Japanese herbal medicines.

Update on Indigestion.

Dyspepsia affects a large percentage of the general population and can lead to lost work productivity and reduced quality of life. Patients with dyspepsia younger than 60 should not routinely undergo endoscopy but instead should pursue Helicobacter pylori test-and-treat approach. For patients 60 and older, endoscopy should be performed. Patients without any identifiable cause for their symptoms are diagnosed with functional dyspepsia. Guideline-based treatment includes H pylori eradication and proton pump inhibitor use. If acid suppression is not adequate, treatment with a tricyclic antidepressant followed by a prokinetic agent and psychological therapy are considered. Complementary therapies are not recommended due to limited evidence.

The clinical efficacy of acupoint sticking combined with massage to treatment functional dyspepsia: A protocol of systematic review and meta-analysis.

BACKGROUND: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of acupoint sticking combined with massage (ASM) in the treatment of functional dyspepsia (FD), and provide clinicians with evidence on which to base their clinical decision making. METHODS: This review will include all studies comparing clinical efficacy of ASM in the treatment of FD. The search strategy will be performed in 10 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is alleviation of global dyspeptic symptoms, alleviation of individual dyspeptic symptoms, quality-of-life improvement, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of ASM in the treatment of FD. CONCLUSION: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of ASM. REGISTRATION NUMBER: INPLASY2020110072 (DOI number: 10.37766/inplasy2020.11.0072).

Electroacupuncture for the treatment of functional dyspepsia: A systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and alternative treatment for patients with FD. This study aimed to explore the effectiveness of EA for the treatment of FD. METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Cochrane Library) for randomized controlled trials of FD treated by EA from inception to February 3, 2020. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. The Cochrane Collaboration's risk of bias tool, RevMan 5.3 software were used for meta-analysis. Data were pooled to calculate relative risk and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data. RESULTS: Seven randomized clinical trials included 853 patients. This meta-analysis investigated the effectiveness of EA alone in the treatment of FD relative to sham-EA or pharmacologic medication (PM). The results showed that EA could significantly improve clinical symptoms. Compared with sham-EA, EA was more effective in reducing symptom scores (SMD -3.44, 95% CI -4.21 to -2.67) and increasing normal slow waves of electrogastrogram (SMD 0.93, 95% CI -0.30 to1.55). When EA was combined with PM, there was no significant difference in reducing symptom scores (SMD -0.18, 95% CI -0.51 to 0.16), increasing the effective rate of clinical symptoms (risk ratio 1.04, 95% CI 0.96 to 1.13), enhancing the level of plasma motilin (SMD 0.93, 95% CI -0.30 to1.55), and reducing gastric half-emptying time (SMD 0.02, 95% CI -0.16 to 0.20). The results also showed that there were very few adverse events reported. CONCLUSION: This meta-analysis suggests that EA is better than the placebo (sham-EA) in treating FD, and the therapeutic effect of EA on FD is equivalent to that of PM on FD. Compared with PM, EA for FD is safer and has fewer adverse reactions. Despite limitations due to the quality and number of the included studies, EA might be used as an effective and safe treatment for FD.

Curative efficacy of extract from Ganjiangdazao recipe on functional dyspepsia in rats.

OBJECTIVE: To evaluate the efficacy of the extract from Ganjiangdazao recipe (EGR) on functional dyspepsia in rats with spleen-stomach deficiency cold pattern (SSDCP) in terms of Traditional Chinese Medicine, and to investigate its pharmacodynamics. METHODS: Sixty Sprague-Dawley rats were randomly divided into the control group, SSDCP group, low-EGR SSDCP group, high-EGR SSDCP group, probiotics group, EGR group. SSDCP model was induced by gavage with the 0 ?edible vinegar. The symptoms and manifestations were scored by method from the relative literature, the ecological changes in cecal microflora was analyzed by 16SrRNA high-throughput sequencing technology, gastric tissues were treated by immunohistochemistry, the levels of related biochemical components related to the gastrointestinal functions were detected by enzyme-linked immunosorbent assay and colorimetry, gastric juice was measured by pH meter, blood pressure measurement by trapping tail method, surface temperature measured by infrared thermal imaging, and the content of 6-gingerol in the serum was determined by liquid-mass chromatography before and after EGR was given. RESULTS: It was found that EGR could effectively relieve the symptoms and manifestations of the SSDCP rats (P < 0.05); the value of the relative abundance of Lactobacillus, Streptococcus, Enterococcus and Coprobacillus increased, while the value of the relative abundance of Clostridium decreased (P < 0.05) in the cecal microflora in the SSDCP rats after high-EGR administration; It was also found that EGR had no substantial effect on the related biochemical components related to the gastrointestinal functions of in the SSDCP rats; and a certain amount of 6-gingerol was detected in the serum of EGR group. CONCLUSION: The pharmacodynamic site of EGR is the intestinal tract, and the mechanism behind the effect of EGR on SSDCP rats, involves increasing the beneficial bacteria and decreasing the proinflammatory bacteria in the intestinal tract. The blood pharmacodynamics of EGR remains to be further studied in the future.

Exploration of the mechanism of traditional Chinese medicine by AI approach using unsupervised machine learning for cellular functional similarity of compounds in heterogeneous networks, XiaoErFuPi granules as an example.

'Polypharmacology' is usually used to describe the network-wide effect of a single compound, but traditional Chinese medicine (TCM) has a polypharmacological effect naturally based on the 'multi-components, multi-targets and multi-pathways' principle. It is a challenge to investigate the polypharmacology mechanism of TCM with multiple components. In this study, we used XiaoErFuPi (XEFP) granules as an example to describe an unsupervised learning strategy for polypharmacology research of TCM and to explore the mechanism of XEFP polypharmacology against multifactorial disease function dyspepsia (FD). Unsupervised clustering of compounds based on similarity evaluation of cellular function fingerprints showed that compounds of TCM without similar targets and chemical structure could also exert similar therapeutic effects on the same disease, as different targets participate in the same pathway closely associated with the pathological process. In this study, we proposed an unsupervised machine learning strategy for exploring the polypharmacology-based mechanism of TCM, utilizing hierarchical clustering based on cellular functional similarity, to establish a connection from the chemical clustering module to cellular function. Meanwhile, FDA-approved drugs against FD were used as references for the mechanism of action (MoA) of FD. First, according to the compound-compound network built by the similarity of cellular function of XEFP compounds and FDA-approved FD drugs, the possible therapeutic function of TCM may represent a known mechanism of FDA-approved drugs. Then, as unsupervised learning, hierarchical clustering of TCM compounds based on cellular function fingerprint similarity could help to classify the compounds into several modules with similar therapeutic functions to investigate the polypharmacology effect of TCM. Furthermore, the integration of quantitative omics data of TCM and approved drugs (from LINCS datasets) provides more quantitative evidence for TCM therapeutic function consistency with approved drugs. A spasmolytic activity experiment was launched to confirm vanillic acid activity to repress smooth muscle contraction; vanillic acid was also predicted to be active compound of XEFP, supporting the accuracy of our strategy. In summary, the approach proposed in this study provides a new unsupervised learning strategy for polypharmacological research investigating TCM by establishing a connection between the compound functional module and drug-activated cellular processes shared with FDA-approved drugs, which may elucidate the unique mechanism of traditional medicine using FDA-approved drugs as references, facilitate the discovery of potential active compounds of TCM and provide new insights into complex diseases.

Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonomic and central nervous systems in functional dyspepsia.

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.

Effects and mechanisms of acupuncture and electroacupuncture for functional dyspepsia: A systematic review.

BACKGROUND: Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or electroacupuncture (EA) seems to be a promising therapy for patients with FD. However, there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD. AIM: To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD. METHODS: A systematic search of the literature was performed to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science. Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3. RESULTS: Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research. Positive effects of acupuncture and EA were observed in regulating gastric motility, gastric accommodation, mental status, gastrointestinal hormones, and central and autonomic functions while improving dyspeptic symptoms and quality of life. CONCLUSION: The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD. However, high-quality studies with well-planned designs are necessary to provide more credible evidence.

Effect of Acupuncture for Postprandial Distress Syndrome: A Randomized Clinical Trial.

BACKGROUND: Postprandial distress syndrome (PDS) is the most common subtype of functional dyspepsia. Acupuncture is commonly used to treat PDS, but its effect is uncertain because of the poor quality of prior studies. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture in patients with PDS. DESIGN: Multicenter, 2-group, randomized clinical trial. (ISRCTN registry number: ISRCTN12511434). SETTING: 5 tertiary hospitals in China. PARTICIPANTS: Chinese patients aged 18 to 65 years meeting Rome IV criteria for PDS. INTERVENTION: 12 sessions of acupuncture or sham acupuncture over 4 weeks. MEASUREMENTS: The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms: postprandial fullness, upper abdominal bloating, and early satiation after 4 weeks of treatment. Participants were followed until week 16. RESULTS: Among the 278 randomly assigned participants, 228 (82%) completed outcome measurements at week 16. The estimated response rate from generalized linear mixed models at week 4 was 83.0% in the acupuncture group versus 51.6% in the sham acupuncture group (difference, 31.4 percentage points [95% CI, 20.3 to 42.5 percentage points]; P < 0.001). The estimated elimination rate of all 3 cardinal symptoms was 27.8% in the acupuncture group versus 17.3% in the sham acupuncture group (difference, 10.5 percentage points [CI, 0.08 to 20.9 percentage points]; P = 0.034). The efficacy of acupuncture was maintained during the 12-week posttreatment follow-up. There were no serious adverse events. LIMITATION: Lack of objective outcomes and daily measurement, high dropout rate, and inability to blind acupuncturists. CONCLUSION: Among patients with PDS, acupuncture resulted in increased response rate and elimination rate of all 3 cardinal symptoms compared with sham acupuncture, with sustained efficacy over 12 weeks in patients who received thrice-weekly acupuncture for 4 weeks. PRIMARY FUNDING SOURCE: Beijing Municipal Science and Technology Commission.

Efficacy of compatible acupoints and single acupoint versus sham acupuncture for functional dyspepsia: study protocol for a randomized controlled trial.

BACKGROUND: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD). METHODS: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019.

Modified Liu-Jun-Zi decoction alleviates visceral hypersensitivity in functional dyspepsia by regulating EC cell-5HT3r signaling in duodenum.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Liu-Jun-Zi (MLJZ) is derived from one of the most famous traditional Chinese prescription Liu-Jun-Zi. It exhibits therapeutic effects in functional dyspepsia (FD), but the underlying mechanisms remain not well understood. Enterochromaffin (EC) cells contribute to the pathogeneses of visceral hypersensitivity in functional gastrointestinal disorders. But whether and how EC cells in duodenum participate in the mechanism of FD remain unsettled. AIM OF THE STUDY: To detect the crucial factors related to EC cells, and to evaluate the therapeutic effect of MLJZ and to determine whether MLJZ relieves visceral hypersensitivity in FD by regulating EC cell-5-hydroxytryptamine 3 receptor (5HT3r) signaling. MATERIALS AND METHODS: FD rats were established by iodoacetamide gavage combined with tail clamping method. The verification of FD model and the evaluation of the therapeutic effect of MLJZ was taken place by hematoxylin-eosin (HE) staining and visceral sensitivity measurement. The expression of EC cells and 5-hydroxytryptamine (5HT) in duodenum was detected by Immunohistochemistry (IHC) staining and enzyme-linked immunosorbent assay (ELISA). IHC staining and quantitative polymerase chain reaction (qPCR) were applied to measure the expression of tryptophan hydroxylase-1 (TPH1), paired box gene 4 (PAX4), transient receptor potential A1 (TRPA1), transient receptor potential C4 (TRPC4) and 5HT3r. Duodenum sections were stained by double immunofluorescence (IF) to study the synthesis of 5HT in EC cells. RESULTS: The gastric sensitivity increased in FD rats while MLJZ decoction significantly attenuated visceral hypersensitivity. The duodenum of FD rats displayed increased expressions of EC cells, 5HT, TPH1, PAX4 and 5HT3r. And the overexpression was reduced in response to MLJZ decoction treatment. CONCLUSIONS: EC cell-5HT3r signaling pathway is abnormally active in FD with visceral hypersensitivity. And MLJZ decoction can alleviates visceral hypersensitivity in FD by regulating EC cell-5HT3r signaling in duodenum.

Drugs under development for the treatment of functional dyspepsia and related disorders.

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.

[Diagnostic and therapeutic approach to dyspepsia and functional dyspepsia:what's new in 2019?] / Enfoque diagnóstico y terapéutico de dispepsia y dispepsia funcional:¿qué hay nuevo en el 2019?

Dyspepsia encompasses a set of symptoms that originate in the gastroduodenal region. It is characterized by pain or epigastric burning, early satiety and post-prandial fullness. According to the relationship of symptoms with meals, it is divided into epigastric pain syndrome and postprandial distress syndrome. However, in clinical practice, they frequently overlap. In recent years the paradigm of gastric physiological alterations has been changed and evidence supporting duodenal eosinophilia has increased, as a primary alteration that alters gastric physiology and can induce symptomatology. Every day there is more interest in the alteration of the microbiota. The treatment is based on the suppression of acid, neuromodulators, prokinetics, psychotherapy, alternative and complementary therapies. No treatment is effective in all patients.

Child compound Endothelium corneum attenuates gastrointestinal dysmotility through regulating the homeostasis of brain-gut-microbiota axis in functional dyspepsia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. MATERIALS AND METHODS: FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. RESULTS: CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CONCLUSION: CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment.

Enfoque diagnóstico y terapéutico de dispepsia y dispepsia funcional: ¿qué hay nuevo en el 2019? / Diagnostic and therapeutic approach to dyspepsia and functional dyspepsia: what's new in 2019?

La dispepsia abarca un conjunto de síntomas que se originan en la región gastroduodenal. Se caracteriza por dolor o ardor epigástrico, saciedad precoz y llenura pos-prandial. Según la relación de los síntomas con las comidas se divide en síndrome de dolor epigástrico y síndrome de malestar pos-prandial. Sin embargo, en la práctica clínica, frecuentemente se sobreponen. En los últimos años se ha cambiado el paradigma de las alteraciones fisiológicas gástricas y han aumentado las evidencias que apoya a la eosinofilia duodenal, como una alteración primaria que altera la fisiología gástrica y puede inducir la sintomatología. Así mismo, cada día hay mayor interés en la alteración de la microbiota. El tratamiento se basa en la supresión de ácido, procinéticos, neuromoduladores, psicoterapia, terapias alternativas y complementarias. Ningún tratamiento es universalmente eficaz en todos los pacientes.

Dyspepsia encompasses a set of symptoms that originate in the gastroduodenal region. It is characterized by pain or epigastric burning, early satiety and post-prandial fullness. According to the relationship of symptoms with meals, it is divided into epigastric pain syndrome and postprandial distress syndrome. However, in clinical practice, they frequently overlap. In recent years the paradigm of gastric physiological alterations has been changed and evidence supporting duodenal eosinophilia has increased, as a primary alteration that alters gastric physiology and can induce symptomatology. Every day there is more interest in the alteration of the microbiota. The treatment is based on the suppression of acid, neuromodulators, prokinetics, psychotherapy, alternative and complementary therapies. No treatment is effective in all patients.

Review article: treatment options for functional dyspepsia.

BACKGROUND: Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia. AIM: To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia. METHODS: A literature search was conducted on Pubmed and other sources to identify relevant studies. RESULTS: Acid suppressive therapy reduced symptoms in 30%-70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2 -antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%-81% responder rate for dopamine receptor antagonists, 32%-91% for serotonin-4-receptor agonists and 31%-80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%-82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%-71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%-91%, rikkunshito in 29%-34% and iberogast in 20%-95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse. CONCLUSIONS: None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.

Efficacy of acupuncture versus sham acupuncture for postprandial distress syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Postprandial distress syndrome (PDS) has a considerable impact on quality of life. Our previous pilot trial suggested that acupuncture might be a potential treatment option for PDS. We will conduct this large trial to determine the efficacy of acupuncture versus sham acupuncture for PDS. METHODS/DESIGN: A total of 280 eligible patients who meet the Rome IV criteria for PDS will be randomly allocated to either the acupuncture group or the sham acupuncture group. Each patient will receive 12 sessions over four weeks. The primary outcomes will be the response rate of overall treatment effect (OTE) and the elimination rate of all three cardinal symptoms (postprandial fullness, upper abdominal bloating, and early satiation) at four weeks after randomization. Secondary outcomes will include assessments of the severity of dyspepsia symptoms and disease-specific quality of life at weeks 4, 8, and 16 after randomization. All patients who receive randomization will be included in the intent-to-treat analysis. DISCUSSION: The finding of this trial will provide high-quality evidence on the efficacy of acupuncture for treatment of PDS. Results of this research will be published in peer-reviewed journals. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN12511434 . Registered on 31 March 2017.

The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).