Disorders of gut-brain interaction are a new challenge of our increasingly complex society, with worldwide repercussions

Abstract

The term disorders of gut-brain interaction (DGBIs) encompasses gastrointestinal disorders that globally affect more than one third of all people. The Rome IV criteria replaced the former term “functional gastrointestinal disorders.“ DGBIs can seriously challenge health and quality of life (QoL). A traditional but outdated approach differentiated “organic” vs “functional“ disorders, seen by some as real vs psychiatric or undefined ones. This traditional distinction did not help patients whose health and QoL are seriously affected. DGBIs include motility disturbance; visceral hypersensitivity; altered mucosal and immune function; altered central nervous system processing, and more. Several DGBIs affect both children and adolescents. DGBIs are characterized by clusters of symptoms. Their pathophysiology relates to combinations of altered motility, visceral sensitivity, mucosal immune function, and more. Routine investigations find no structural abnormality that would easily explain the symptoms. Symptom-based criteria were developed to better understand patients where no mechanistic explanation was available for clinical practice and inclusion into clinical trials. To understand DGBIs and to find ways to treat them, these rigid mechanistic views fall short.

Key Words: Disorders of gut-brain interaction; American Psychiatric Association; Rome foundation; Rome IV; Gut-brain-axis; Functional diseases; Psychiatric diseases; Mechanistic approaches; Symptom-based criteria; Clinical trials; Drugs; Biologics

Core Tip: Disorders of gut-brain interaction can seriously challenge patients‘ health and quality of life (QoL). This new approach no longer differentiates organic from functional (or psychiatric) disorders. This former, now outdated distinction did not help patients whose QoL was and is seriously impaired. Instead, todays symptom-based criteria attempts to better understand patients. The traditional explanations did not allow satisfying clinical treatment nor inclusion into exploratory trials with new drugs or biologics. With this new approach, the hope is to overcome the shortcomings of traditional approaches.

INTRODUCTION

The term disorders of gut-brain interaction (DGBIs) encompasses many gastrointestinal disorders that together affect more than one third of people worldwide. DGBIs account for at least one-third of the referrals made to gastroenterology clinics[1]. The new term DGBIs was established by the Rome Foundation[2] and replaced since 2016 the former term “functional gastrointestinal disorders“[3]. DGBIs can seriously affect health and quality of life (QoL). Traditionally, it was assumed that there were either organic or functional, nonstructural disorders, assuming often a difference between real opposed to psychiatric health challenges. This distinction did not help those patients whose health and QoL was affected so much that participation in the working place and in social interaction were seriously impaired. Irritable bowel syndrome and functional dyspepsia are the most commonly recognized and researched DGBIs, but there are in total 33 DGBIs which can arise from any part of the gastrointestinal tract, including the esophagus, gastroduodenum, bowel, biliary, and anorectum[4]. Living with a chronic gastrointestinal disorder can be burdensome and seriously impact important life domains. Therefore, such disorders represent complex challenges to patients, to our increasingly complex society in general, and healthcare providers[5].

DGBIS

DGBIs includes motility disturbance; visceral hypersensitivity; altered mucosal and immune function; altered gut microbiomes; altered central nervous system (CNS) processing, and more. Several of these disorders also affect children and adolescents[2,6]. Symptoms include abdominal pain, bloating, diarrhea and constipation, and may overlap with or exacerbate primary eating disorder symptoms, leading to a decreased QoL. Patients with DGBIs often experience concerns related to eating, and the connection between DGBI symptoms and eating disorders is increasingly acknowledged[7]. DGBIs are characterized by patterns of symptoms. Their pathophysiology relates to combinations of altered motility, visceral sensitivity, epithelial barrier, mucosal immune function, microbiome, or gut-CNS neural processing. Routine investigations find in these symptom patterns neither underlying structural abnormalities that would easily explain the symptoms, nor biochemical abnormalities. The development of symptom-based criteria arose because of the need to identify patients who had gastrointestinal symptoms for which there was no mechanistic, biochemical, or imaging explanation for diagnosis in clinical practice and for selection in clinical trials[1,8].

On the one hand, the instincts of the digestive system have developed over millions of years. On the other hand, what our brain receives in the form of information, ideas, the latest trends, entertainment and much more through participation in intellectual life is undergoing an ever faster development process. It began with the emergence of modern man and has accelerated ever more with the Renaissance, industrialization and globalization. Also, the nourishment to which our digestive system is physically exposed has fundamentally changed with industrialization.

The medical literature oscillates between investigations into nutrition[9], the gut microbiome[10], the spiritual trends and waves that reach us via social media[11], the more traditional mass media including the press, radio, TV, and further individual factors. In recent years, there has been a global increase in the consumption of ultra-processed foods, found in industrial formulations like ready-to-eat meals, sugary beverages and snacks; they are typically high in fat, sugar, added flavorings, dyes and additives, often replacing fresh, whole foods, and characterized by high levels of sugar, fat and salt, along with additives and preservatives. Such ultra-processed foods are becoming a dominant part of dietary intake, especially among children and adolescents[7].

Although DGBIs are common, our knowledge about their physiopathology is still poor. So far, no valid tools have been established to evaluate them in young patients. A recent publication describes the development of a psycho-gastroenterological questionnaire to assess the psycho-gastroenterological profile and social characteristics of pediatric patients with and without DGBIs in Italy and thus adds valuable information[12].

The gut microbiome, a key regulator of gut–brain interaction, is the collection of bacteria, viruses, archaea, and eukaryotes that reside in the human intestinal environment. After rapid colonization at birth, the human gut microbiome changes throughout the first 2 years of life, diversifies and then stabilizes into adulthood. Over the past decades, our understanding of the gut-brain axis has grown strongly. Different microbes and their metabolites play a crucial role in a variety of patient subsets, driving specific symptoms such as abdominal pain or dysmotility[10].

As social media has rapidly become a ubiquitous, pervasive part of the lives of most people worldwide, this brings both benefits as well as health misinformation, reinforcement of abnormal sick-role behavior, and undermines the legitimacy of psychological care[11].

QoL is a broad multidimensional concept with several dimensions such as lower levels of psychological distress, greater physical and social functioning, general mental and physical health, and vitality. The chronicity of gastrointestinal symptoms, the lack of structural organic features, and healthcare-related costs greatly impact the QoL of patients with a DGBI. Furthermore, DGBI patients have significant impairment in both mental and physical components of QoL. Research about variables that explain reductions in QoL among those with DGBIs is ongoing[1].

Many patients continue to experience high symptom burden despite conventional treatments. Non-conventional treatment approaches are increasingly popular among patients with GI disorders given their potential to improve symptoms and enhance QoL. Such approaches range from nutritional strategies and psychological interventions to mind-body practices, addressing different facets of a patient’s overall health[5].

DGBIs often originate in childhood. They persist into adulthood in up to twenty percent of patients, suggesting that monitoring into adulthood might make sense. Those diagnosed with anxiety or mood disorders in childhood need particular attention. Prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously[13].

Eating disorders represent a problem of growing importance within public health and in the scientific and media spheres because of their increasingly early onset and their complex multifactorial etiology. They are classified by the diagnostic criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, Text Revision[14], published by the American Psychiatric Association[15]. The most frequent eating challenges are anorexia nervosa, bulimia nervosa, and binge eating disorders[16].

New research approaches include the investigation of neural interfaces in the hope to bridge the brain to the world beyond healthcare. This new look is emerging at the intersection of neurotechnology and urban planning and might be able to transform or at least to modify how we interact with our physical and social surroundings. Recording and decoding neural signals might help to facilitate direct connections between the brain and external devices, enabling seamless information exchange and shared experiences[17]. These new approaches are still in their infancy.

CONCLUSION

Teaching on DGBIs within the undergraduate and postgraduate medical education system does not reflect the prevalence and burden of these disorders. Medical students and physicians are in general not being adequately trained to look after the most common gastrointestinal conditions[4].

Managing patients’ symptoms requires a multidisciplinary approach. It is important to emphasize that gastrointestinal symptoms in patients with anorexia nervosa are often linked to malnutrition or purging behaviors. Age-appropriate diagnostic tools such as the Rome IV Diagnostic Questionnaire are crucial to better understand this relationship in younger populations. This allows more tailored approaches to the diagnosis and management of DGBIs in children and adolescents[7,12,18].