Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups.

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.

Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When.

Irritable bowel syndrome (IBS) is responsive to treatments using central neuromodulators. Central neuromodulators work by enhancing the synaptic transmission of 5-hydroxytryptamine, noradrenalin, and dopamine, achieving a slower regulation or desensitization of their postsynaptic receptors. Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals, and enhancing neurogenesis in patients with IBS. Choosing a central neuromodulator for treating IBS should be according to the pharmacological properties and predominant symptoms. The first-line treatment for pain management in IBS is using tricyclic antidepressants. An alternative for pain management is the serotonin and noradrenaline reuptake inhibitors. Selective serotonin reuptake inhibitors are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain. The predominant bowel habit is helpful when choosing a neuromodulator to treat IBS; selective serotonin reuptake inhibitors help constipation, not pain, but may cause diarrhea; tricyclic antidepressants help diarrhea but may cause constipation. A clinical response may occur in 6-8 weeks, but long-term treatment (usually 6-12 months) is required after the initial response to prevent relapse. Augmentation therapy may be beneficial when the therapeutic effect of the first agent is incomplete or associated with side effects. It is recommended to reduce the dose of the first agent and add a second complementary treatment. This may include an atypical antipsychotic or brain-gut behavioral treatment. When tapering central neuromodulators, the dose should be reduced slowly over 4 weeks but may take longer when discontinuation effects occur.

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.

A Review of the Evidence and Recommendations on Communication Skills and the Patient-Provider Relationship: A Rome Foundation Working Team Report.

BACKGROUND & AIMS: Over several decades, changes in health care have negatively impacted meaningful communication between the patient and provider and adversely affected their relationship. Under increasing time pressure, physicians rely more on technology than face-to-face time gathering data to make clinical decisions. As a result, they find it more challenging to understand the illness context and fully address patient needs. Patients experience dissatisfaction and a diminution of their role in the care process. For patients with disorders of gut-brain interaction, stigma leads to greater care dissatisfaction, as there is no apparent structural basis to legitimize the symptoms. Recent evidence suggests that practical communication skills can improve the patient-provider relationship (PPR) and clinical outcomes, but these data are limited. METHODS: The Rome Foundation convened a multidisciplinary working team to review the scientific evidence with the following aims: a) to study the effect of communication skills on patient satisfaction and outcomes by performing an evidence-based review; b) to characterize the influence of sociocultural factors, health care system constraints, patient perspective, and telehealth on the PPR; c) to review the measurement and impact of communication skills training on these outcomes; and d) to make recommendations to improve communication skills training and the PPR. RESULTS: Evidence supports the fact that interventions targeting patient-provider interactions improve population health, patient and provider experience, and costs. Communication skills training leads to improved patient satisfaction and outcomes. The following are relevant factors to consider in establishing an effective PPR: addressing health care system constraints; incorporating sociocultural factors and the role of gender, age, and chronic illness; and considering the changing role of telehealth on the PPR. CONCLUSIONS: We concluded that effective communication skills can improve the PPR and health outcomes. This is an achievable goal through training and system change. More research is needed to confirm these findings.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Functional gastrointestinal disorders: advances in understanding and management.

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.

Improving Patient-Provider Relationships to Improve Health Care.

Changes in our health care system have posed challenges for the patient-provider relationship (PPR) and may have negative consequences. For the clinician, due to lower reimbursements from third party payers, and increased administrative tasks such as the electronic medical record (EMR) and certification requirements, clinic visit time is now one-fifth that of decades ago. Clinicians may order diagnostic studies and imaging as a substitute for face to face time as it is seen to save time and increase relative value units (RVUs). As a result, the medical interview is very abbreviated, and the physical examination is disappearing. This occurs at the expense of the physician-patient relationship. Now there is limited time to gather relevant information, to understand the context of the illness, and address patient needs. For the clinician there is reduced satisfaction, loss of the meaningfulness of caring for patients, and possibly increased risk for burnout, and malpractice. This may lead to negative attitudes and behaviors toward patients, particularly for those with nonstructural diagnoses (eg, disorders of gut-brain interaction) which are given lower priority than those with acute or structural illness. In turn, patients experience a diminution in their role in the relationship and respond to adverse clinician behaviors with a lack of connection, frustration, and at times self-blame and stigmatization. To reverse this downward trend and re-establish an effective PPR changes are needed: 1) improving educational methods to provide skills to enhance patient-centered care, 2) incentivizing educators who teach and clinicians who practice patient-centered care, and 3) research support to demonstrate successful outcomes in satisfaction, adherence and clinical outcomes.

Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report.

BACKGROUND & AIMS: Central neuromodulators (antidepressants, antipsychotics, and other central nervous system-targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut-brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations. METHODS: The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee. RESULTS: The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6-12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient-provider relationship. CONCLUSIONS: Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.

Diagnosis and Treatment of Rumination Syndrome: A Critical Review.

Rumination syndrome (RS) is characterized by the repeated regurgitation of material during or soon after eating with the subsequent rechewing, reswallowing, or spitting out of the regurgitated material. Rumination syndrome is classified as both a "Functional Gastroduodenal Disorder" (by the Rome Foundation's Functional Gastrointestinal Disorders: Disorders of Gut-Brain Interaction, 4th edition) and a "Feeding and Eating Disorder" (by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition). Rumination syndrome is a disorder that is often inaccurately diagnosed or missed, resulting in patients experiencing protracted symptoms and not receiving treatment for long periods. There is a lack of clear consensus for RS diagnosis, mechanisms that maintain RS, and treatment. Guided by existing research and our clinical expertise, we synthesize available evidence and provide recommendations for clinical use. We present a case example and critically summarize the literature to date to (i) increase clinicians' understanding of heterogeneous clinical presentations, (ii) suggest assessment strategies to facilitate accurate diagnosis, and (iii) provide a schematic for intervention options. Overall, we recommend clinicians recognize the heterogeneous features of RS when considering diagnosis, assess for RS symptoms by clinical history, and treat RS with targeted diaphragmatic breathing while using other methods as augmented intervention or alternative treatment.

Psychotropics, Antidepressants, and Visceral Analgesics in Functional Gastrointestinal Disorders.

PURPOSE OF REVIEW: The functional gastrointestinal disorders, or disorders of gut-brain interaction as defined by the Rome IV criteria, are the most common diagnostic entities in gastroenterology. Treatments that address the dysregulation of gut-brain interaction with these disorders are increasingly gaining interest as a better option than for example traditional analgesics, particularly opioids. Antidepressants, antianxiety and antipsychotic medications, and visceral analgesics, now termed neuromodulators, are included in this update addressing the evidence of treatment benefit in disorders of brain-gut interaction. RECENT FINDINGS: By a careful selection based on a multidimensional clinical profile, a decreased symptom burden, particularly regarding abdominal pain, nausea, and vomiting, as well as improved social function and quality of life, can be obtained by use of neuromodulators. There is good evidence for the peripheral neuromodulators from studies in bowel disorders, and the central neuromodulators both from indirect evidence in chronic pain disorders as well as selected disorders of brain-gut interaction. Basic knowledge about the pharmacologic properties and clinical use of neuromodulators in disorders of brain-gut interaction improves the treatment outcome and avoids use of traditional analgesics.

Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes.

Objective: The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods: In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results: In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions: The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.

Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV.

Functional gastrointestinal disorders (FGIDs), the most common diagnoses in gastroenterology are recognized by morphological and physiological abnormalities that often occur in combination including motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota and altered central nervous system processing. Research on these gut-brain interaction disorders is based on using specific diagnostic criteria. The Rome Foundation has played a pivotal role in creating diagnostic criteria thus operationalizing the dissemination of new knowledge in the field of FGIDs. Rome IV is a compendium of the knowledge accumulated since Rome III was published 10 years ago. It improves upon Rome III by: 1) updating the basic and clinical literature, 2) offering new information on gut microenvironment, gut-brain interactions, pharmacogenomics, biopsychosocial, gender and cross cultural understandings of FGIDs, 3) reduces the use of imprecise and occassionally stigmatizing terms when possible, 4) uses updated diagnostic algorithms, 5) incorporates information on the patient illness experience, and physiological subgroups or biomarkers that might lead to more targeted treatment. This introductory article sets the stage for the remaining 17 articles that follow and offers an historical overview of the FGIDs field, differentiates FGIDs from motility and structural disorders, discusses the changes from Rome III, reviews the Rome committee process, provides a biopsychosocial pathophysiological conceptualization of FGIDs, and offers an approach to patient care.

Centrally Mediated Disorders of Gastrointestinal Pain.

Centrally Mediated Abdominal Pain Syndrome (CAPS), formerly known as Functional Abdominal Pain Syndrome, can be distinguished from other functional GI disorders by its strong central component and relative independence from motility disturbances. CAPS is a result of central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability. A newly described condition, Narcotic Bowel Syndrome (NBS)/Opioid-Induced GI Hyperalgesia, is characterized by the paradoxical development of or increases in abdominal pain associated with continuous or increasing dosages of opioids. Patients only have relief when opioids are withdrawn. We define both conditions in the context of epidemiology, pathophysiology, clinical evaluation and treatment, emphasizing the importance of a physician-patient relationship in all aspects of care.

Biopsychosocial Aspects of Functional Gastrointestinal Disorders.

In this paper, we provide a general framework for understanding the functional gastrointestinal disorders (FGID) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of the FGID. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors - the environment, including the influence of those in an individual's family, the individual's own psychological states and traits, and the individual's (neuro)physiological make-up - interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools which can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGID.

Central Neuromodulators for Treating Functional GI Disorders: A Primer.

Patients with functional GI disorders (FGIDs) are commonplace in the gastroenterologist's practice. A number of these patients may be refractory to peripherally acting agents, yet respond to central neuromodulators. There are benefits and potential adverse effects to using TCAs, SSRIs, SNRIs, atypical antipsychotics, and miscellaneous central neuromodulators in these patients. These agents can benefit mood, pain, diarrhea, constipation, nausea, sleep, and depression. The mechanisms by which they work, the differences between classes and individual agents, and the various adverse effects are outlined. Dosing, augmentation strategies, and treatment scenarios specifically for painful FGIDs, FD with PDS, and chronic nausea and vomiting syndrome are outlined.

Psychological Factors May Play an Important Role in Pediatric Crohn's Disease Symptoms and Disability.

OBJECTIVE: To examine the relative contributions of disease activity and psychological factors to self-reported symptoms and disability in children with Crohn's disease. STUDY DESIGN: Participants (n = 127 children age 8-18 years) completed questionnaires on symptom severity and disability, as well as psychological measures assessing anxiety, depression, pain beliefs and coping. Disease activity was measured by the Pediatric Crohn's Disease Activity Index. Structural equation modeling was used to test the effects of disease activity and psychological factors on symptoms and disability. RESULTS: In the hypothesized model predicting symptoms, psychological factors (ß = 0.58; P < .001) were significantly associated with disease symptoms but disease activity was not. The model for disability yielded significant associations for both psychological factors (ß = 0.75; P < .001) and disease activity (ß = 0.61, P < .05). CONCLUSION: Crohn's disease symptoms in children and adolescents are not only driven by disease activity. Coping, anxiety, depression, and cognition of illness are important in the patient-reporting of symptom severity and disability. Physicians need to be aware that symptom self-reporting can be driven by psychological factors and may not always be simply an indicator of disease activity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00679003.

A Perspective on Brain-Gut Communication: The American Gastroenterology Association and American Psychosomatic Society Joint Symposium on Brain-Gut Interactions and the Intestinal Microenvironment.

BACKGROUND: Alterations in brain-gut communication and the intestinal microenvironment have been implicated in a variety of medical and neuropsychiatric diseases. Three central areas require basic and clinical research: (1) how the intestinal microenvironment interacts with the host immune system, central nervous system, and enteric nervous system; (2) the role of the intestinal microenvironment in the pathogenesis of medical and neuropsychiatric disease; and (3) the effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the intestinal microenvironment and the treatment of disease. METHODS: This review article is based on a symposium convened by the American Gastroenterology Association and the American Psychosomatic Society to foster interest in the role of the intestinal microenvironment in brain-gut communication and pathogenesis of neuropsychiatric and biopsychosocial disorders. The aims were to define the state of the art of the current scientific knowledge base and to identify guidelines and future directions for new research in this area. RESULTS: This review provides a characterization of the intestinal microbial composition and function. We also provide evidence for the interactions between the intestinal microbiome, the host, and the environment. The role of the intestinal microbiome in medical and neuropsychiatric diseases is reviewed as well as the treatment effects of manipulation of the intestinal microbiome. CONCLUSIONS: Based on this review, opportunities and challenges for conducting research in the field are described, leading to potential avenues for future research.