A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction.

BACKGROUND AND AIMS: This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). METHODS: The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. RESULTS: We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. CONCLUSIONS: Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT.

Influence of Tilia tomentosa Moench Extract on Mouse Small Intestine Neuromuscular Contractility.

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5-36 µg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 µg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.

Effect of herbal medicine daikenchuto on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: A prospective randomized study.

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated.

Nutritional Aspects of Pediatric Gastrointestinal Diseases.

In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively "harmless" nature. Apart from a diet's therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical "side effects", however, it should be emphasized that any dietary modification might have negative consequences on children's growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.

The effect of probiotic supplementation on performance, inflammatory markers and gastro-intestinal symptoms in elite road cyclists.

BACKGROUND: Elite athletes may suffer from impaired immune function and gastro-intestinal (GI) symptoms, which may affect their health and may impede their performance. These symptoms may be reduced by multi-strain probiotic supplementation. Therefore, the aim of the current study is to examine the effects of probiotic supplementation on aerobic fitness characteristics, inflammatory markers and incidence and severity of GI symptoms in elite cyclists. METHODS: Twenty-seven male cyclists, ranked elite or category 1 level competitions, were randomly assigned to a multi-strain probiotic-supplemented group (E, n = 11) or placebo group (C, n = 16). All participants visited the laboratory at the beginning of the study and following 90 d of supplementation/placebo. Prior to testing, all participants completed a GI symptoms questionnaire and underwent physical and medical examination, and anthropometric measurements. Venous blood was drawn for inflammatory markers analysis. The cyclists then underwent maximal oxygen consumption (VO2max) test and time-to-fatigue (TTF) test at 85 % of maximal power, 3 h following the VO2max test. All testing procedures were repeated after 90 d of probiotic / placebo treatment (double blind design). RESULTS: Lower incidence of nausea, belching, and vomiting (P < 0.05) at rest, and decreased incidence of GI symptoms during training were found in E group vs. C Group, respectively (∆GI -0.27 ± 0.47 % vs. 0.08 ± 0.29 %, P = 0.03), no significant changes were observed in the incidence of total overall GI symptoms (∆GI -5.6 ± 14.7 % vs. 2.6 ± 11.6 %, P = 0.602) Mean rate of perceived exertion (RPE) values during the TTF were lower in E group (∆RPE: -0.3 ± 0.9 vs. 0.8 ± 1.5, P = 0.04). No significant changes were measured between and within groups in VO2max and TTF values, mean levels of C-reactive protein (CRP), IL-6-and tumor necrosis factor alpha (TNFα) values following treatment. CONCLUSIONS: Probiotics supplementation may have beneficial effects on GI symptoms in elite cyclists. Future studies, using higher doses and during different training seasons, might help understanding the effects of probiotic supplementation on elite athletes' health and performance. TRIAL REGISTRATION: NIH clinicaltrial.gov #NCT02756221 Registered 25 April 2016.

Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence.

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation.

Allomyrina dichotoma larval extract has protective effects against gut permeability of dextran sulfate sodium-fed Drosophila by E-cadherin and armadillo.

ETHNOPHARMACOLOGICAL RELEVANCE: Larvae of the rhinoceros beetle (Allomyrina dichotoma) (ADL) are used ethnopharmacologically to treat gut-related disorders in Korea and China since 1596 and are also approved as a safe novel food with high nutritional value. AIM OF THE STUDY: We investigated the protective effects of ADL extract against leaky gut disease using a Drosophila model and sought to elucidate the underlying biological mechanisms. MATERIALS AND METHODS: We examined the protective effects of ADL extract (2 mg/mL) against the leaky gut disease using a dextran sulfate sodium (DSS)-induced leaky gut Drosophila melanogaster model. RESULTS: We found that oral administration of ADL extracts significantly increase the survival rate of DSS-fed Drosophila. Under conditions of DSS-induced gut damage, ADL extract reduced gut cell apoptosis and gut permeability, resulting in the maintenance of gut tissue homeostasis. Furthermore, we observed that oral administration of ADL extract can induce high levels of E-cadherin gene expression and also restored the original membrane localization of DSS-disrupted E-cadherin contiguous with the armadillo. CONCLUSION: We concluded that ADL extract plays an important role in maintaining gut homeostasis through the up-regulation of E-cadherin and that it may have a protective effect against leaky gut syndrome.

The Effect of Abdominal Massage on Gastrointestinal Functions: a Systematic Review.

INTRODUCTION: abdominal massage with regular and rhythmic movements has been used to treat some symptoms of diseases. OBJECTIVES: to review data collected from randomized controlled trials regarding the effect of abdominal massage (AM) on gastrointestinal functions (GFs). METHODS: we conducted a systematic review of articles accessible through PubMed, Scopus, Science Direct, Google Scholar, and Web of Science. All eligible English RCT- published articles related to the effect of AM on GFs were included in the study from the time of their acceptance until June 2019. RESULTS: ten studies with 464 patients met the inclusion criteria. Three studies reported that AM alleviated constipation symptoms in patients with multiple sclerosis, cancer, and elderly adults. In three studies, AM increased bowel movements in people with constipation and patients undergoing skeletal traction. The results of three studies conducted on intensive care patients showed that AM improved GFs, and decreased abdominal circumference and distension. Two studies showed the effectiveness of AM in reducing the gastric residual volume. However, one study indicated no significant difference between the intervention and control groups. The results of two studies showed that AM did not affect laxative intake, nausea or vomiting, frequency of defecation, and food intake. Furthermore, AM did not decrease ventilator-associated pneumonia in patients undergoing mechanical ventilation. The studies reported no adverse effects of AM. CONCLUSIONS: there was promising evidence for the effect of AM on GFs. However, further studies are needed to measure the unknown dimensions of AM in patients.

Impaired Vagal Efficiency Predicts Auricular Neurostimulation Response in Adolescent Functional Abdominal Pain Disorders.

INTRODUCTION: To determine whether pretreatment vagal efficiency (VE), respiratory sinus arrhythmia, and heart period can predict pain improvement with auricular neurostimulation in pediatric functional abdominal pain disorders. METHODS: A total of 92 adolescents with functional abdominal pain disorders underwent a 4-week randomized, double-blinded, sham-controlled auricular neurostimulation trial. Electrocardiogram-derived variables at baseline were used to predict pain using mixed effects modeling. RESULTS: A 3-way interaction (95% confidence intervals: 0.004-0.494) showed that the treatment group subjects with low baseline VE had lower pain scores at week 3. There was no substantial change in the placebo or high VE treatment group subjects. This effect was supported by a significant correlation between baseline VE and degree of pain reduction only in the treatment group. DISCUSSION: Impaired cardiac vagal regulation measured by VE predicts pain improvement with auricular neurostimulation.

Constipation.

Constipation in otherwise healthy infants and children is a common problem despite confusion about how to precisely define constipation and constipation-related disorders. Constipation may, rarely, be a sign or symptom of a more serious disease or a diagnosis defined only by its symptoms and without any structural or biochemical findings. In the latter case it is classified as a functional gastrointestinal disorder (FGID). FGIDs are defined as disorders that cannot be explained by structural or biochemical findings. The Rome Foundation has standardized diagnostic criteria for all FGIDs. The Rome criteria are based on the available research as well as the clinical experience of the Foundation's assembled experts. The most recent report, Rome IV, described clinical criteria and diagnostic tools and encouraged more rigorous research in the area of FGIDs. The true incidence and prevalence of constipation is difficult to know because it may be treated at home using home remedies or diagnosed at a visit to a primary care provider or to a subspecialist pediatric gastroenterologist. The most recent attempts to define the prevalence of all pediatric FGIDs have been made using the Rome IV criteria. The defined FGID entities that may be associated with the complaint of constipation are infant dyschezia, functional constipation, and nonretentive fecal incontinence. The term encopresis, omitted from Rome IV, is defined by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition The 3 Rome-defined (constipation-related) entities and the APA entity of encopresis are the focus of this review.

Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.

Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.

Hypnosis and Cognitive Behavioral Therapies for the Management of Gastrointestinal Disorders.

PURPOSE OF REVIEW: To review the nature, current evidence of efficacy, recent developments, and future prospects for cognitive behavioral therapy (CBT) and gut-directed hypnotherapy, the two best established psychological interventions for managing gastrointestinal (GI) disorders. RECENT FINDINGS: New large randomized controlled trials are showing that cost-effective therapy delivery formats (telephone-based, Internet-based, fewer therapist sessions, or group therapy) are effective for treating GI disorders. CBT and hypnotherapy can produce substantial improvement in the digestive tract symptoms, psychological well-being, and quality of life of GI patients. However, they have long been hampered by limited scalability and significant cost, and only been sufficiently tested for a few GI health problems. Through adoption of more cost-effective therapy formats and teletherapy, and by expanding the scope of efficacy testing to additional GI treatment targets, these interventions have the potential to become widely available options for improving clinical outcomes for patients with hard-to-treat GI disorders.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease.

The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.

Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge.

The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. These include the functional gastrointestinal disorders (FGID), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn's disease. Although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (PNE)/ psychoneuroimmunology (PNI) remain only loosely connected. We aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. To this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of FGIDs and IBD. From an interdisciplinary PNE/PNI perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of FGID and IBD. We provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease / Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro

ABSTRACT The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.

RESUMO O Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro foi aprovado pela Sociedade Brasileira de Transplante de Medula Óssea, com a participação de 26 centros brasileiros de transplante de células-tronco hematopoiéticas. O Consenso descreve as principais condutas nutricionais em casos de doença do enxerto contra o hospedeiro, a principal complicação do transplante de células-tronco hematopoiéticas.

Effectiveness and safety of light vegetarian diet on functional constipation with gastrointestinal damp-heat pattern: An exploratory study protocol for randomized controlled trial.

INTRODUCTION: Functional constipation (FC) is one of the common gastrointestinal disorders that affects people of almost every age. Persistent FC significantly affects quality of life and well-being along with economic burden on patients as well as health care system. Therapeutic efficacy of currently used treatment strategies becomes limited shortly after their discontinuation as constipation occurs again as a result of inappropriate dietary habits. Previous studies have revealed that light vegetarian diet (LVD) can significantly improve both typical and atypical subtypes of major traditional Chinese medicine (TCM) FC syndrome such as gastrointestinal damp-heat syndrome. This protocol aims at exploratorily investigating effectiveness and safety of LVD following a rigorous clinical trial. METHODS AND DESIGN: Total 92 patients in each of the 2 subtypes will be recruited in China-Japan Friendship Hospital for participating in this prospective, placebo-controlled, randomized trial and exploratory study. The patients in each subtype will be randomly divided into 4 groups according to 1:1:1:1 ratio with allocation concealment, which are drug + diet group, drug group, placebo + diet group and placebo group. Patients in the group with diet intervention will be required to strictly follow the LVD. The study will continue for a period of 28 days, including a drug or placebo supervised intervention and a 14th-day telephone follow-up. During the intervention, patients will be required to record a designed diary for controlling the diet quality (DQ) and analyzing the defecation. The study will focus investigation of complete spontaneous bowel movements (CSBM) per week as its primary outcome and constipation-related symptom rating scale (CSS), TCM syndrome scale (TCMSS), 48-hour gastrointestinal transit time (48-hour GITT), high resolution anorectal manometry (HRAM) and fecal flora detection (FFD) will be included in secondary outcomes. Furthermore, the study will also determine safety, DQ and compliance indicators. ETHICS AND DISSEMINATION: This study has been approved by China-Japan Friendship Hospital clinical research ethics committee (No. 2017-46-1). A SPIRIT checklist is available for this protocol. TRIAL REGISTRATION NUMBER: ChiCTR1800019686 in Chinese Clinical Trial Registry (WHO ICTRP member).

Sleep disturbances and gastrointestinal dysfunction are associated with thalamic atrophy in Parkinson's disease.

BACKGROUND: Non-motor symptoms are common aspects of Parkinson's disease (PD) occurring even at the prodromal stage of the disease and greatly affecting the quality of life. Here, we investigated whether non-motor symptoms burden was associated with cortical thickness and subcortical nuclei volume in PD patients. METHODS: We studied 41 non-demented PD patients. Non-motor symptoms burden was assessed using the Non-Motor Symptoms Scale grading (NMSS). Cortical thickness and subcortical nuclei volume analyses were carried out using Free-Surfer. PD patients were divided into two groups according to the NMSS grading: mild to moderate (NMSS: 0-40) and severe (NMSS: ≥ 41) non-motor symptoms. RESULTS: Thalamic atrophy was associated with higher NMSQ and NMSS total scores. The non-motor symptoms that drove this correlation were sleep/fatigue and gastrointestinal tract dysfunction. We also found that PD patients with severe non-motor symptoms had significant thalamic atrophy compared to the group with mild to moderate non-motor symptoms. CONCLUSIONS: Our findings show that greater non-motor symptom burden is associated with thalamic atrophy in PD. Thalamus plays an important role in processing sensory information including visceral afferent from the gastrointestinal tract and in regulating states of sleep and wakefulness.

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.

Circadian rhythms: a regulator of gastrointestinal health and dysfunction.

INTRODUCTION: Circadian rhythms regulate much of gastrointestinal physiology including cell proliferation, motility, digestion, absorption, and electrolyte balance. Disruption of circadian rhythms can have adverse consequences including the promotion of and/or exacerbation of a wide variety of gastrointestinal disorders and diseases. Areas covered: In this review, we evaluate some of the many gastrointestinal functions that are regulated by circadian rhythms and how dysregulation of these functions may contribute to disease. This review also discusses some common gastrointestinal disorders that are known to be influenced by circadian rhythms as well as speculation about the mechanisms by which circadian rhythm disruption promotes dysfunction and disease pathogenesis. We discuss how knowledge of circadian rhythms and the advent of chrono-nutrition, chrono-pharmacology, and chrono-therapeutics might influence clinical practice. Expert opinion: As our knowledge of circadian biology increases, it may be possible to incorporate strategies that take advantage of circadian rhythms and chronotherapy to prevent and/or treat disease.

Migraine associated with gastrointestinal disorders: A pathophysiological explanation.

BACKGROUND: Migraine is a highly prevalent, disabling, and costly disorder worldwide. From a long time ago, headaches have been known to be associated with gastrointestinal (GI) disorders. Headaches originating from gastric complaints were appreciated by Persian Medicine (PM) scholars. Today, functional GI disorders are shown to have high comorbidity with migraines; however, a causal relationship is not accepted today and pathophysiological explanations for this comorbidity are scarce. Therefore, based on the PM philosophy and the existing evidence, we aimed to propose an explanation for the co-morbidity of migraine and GI disorders. SUMMARY: Noxious stimuli from the GI tract are relayed to the nucleus tractus solitarius (NTS) in the brain stem, which is located close to the trigeminal nucleus caudalis (TNC). TNC has shown projections to (NTS) through which frequent GI stimuli may antidromically reach the TNC and finally result in neurogenic inflammation. In addition, immune products, particularly histamine, are released in the submucosa of the GI tract and absorbed into the systemic circulation, which renders migraineurs more prone to attacks.