Ecology is the science that studies the interactions of organisms with their environment and each other. Two important principles of ecology characterize environmental relations. First, all living organisms have a continual interrelation with other living and nonliving elements that comprise their environment. Second, each of these ecosystems and their components are connected and affect one another.
Sixty years ago, the World Health Organization provided a new dimension to the concept of human health by including physical, psychological, and social components to its definition. In keeping with this holistic concept of health, the biopsychosocial model underscores the relation and equilibrium among biological, physiological, and psychological systems to determine susceptibility to functional gastrointestinal disorders and explain the clinical variability and different responses to treatment (1). This model proposes that illness and disease result from biological, psychological, and social subsystems that interact at multiple levels. In this context, psychosocial factors have direct physiological and pathological consequences. This framework differs from the classical view of a single etiology for each condition. Equilibrium between organ systems and ecosystems results in health, whereas imbalance is experienced as illness.
Our interaction with the environment can be loosely characterized as an interdependent relation between 2 ecosystems. Food antigens and gut flora are examples of the complex internal ecosystem. Relevant examples of the external ecosystem are the surrounding social and physical environment.
Adverse reactions to food are frequently reported by patients with functional gastrointestinal disorders (FGIDs) (2). There are intriguing but still preliminary data indicating a possible role of food hypersensitivity in the pathogenesis of irritable bowel syndrome (IBS). A trial of food elimination based on serum immunoglobulin G4 antibodies in patients with IBS has shown a significant decrease in symptoms, compared with patients receiving a sham diet (3). In line with these findings, another study showed improvement in rectal compliance in patients with IBS undergoing a food-specific immunoglobulin G4 antibody-guided exclusion diet (4).
The gut flora influences our body functions in multiple ways. The flora forms a barrier against pathogens, stimulates the host immune system, limits the adhesion of pathogenic bacteria to the epithelium, and controls the proliferation and differentiation of epithelial cells (5). Germ-free rats have different spatial and temporal characteristics of migrating motor complexes in the small intestine than do conventional animals (6). Anaerobic bacteria seem to be an important promoter of regular spike activity in the small intestine. Psychological stress results in quantitative alterations in bacteria (7,8). Stressed mice exhibit a decrease in the relative proportion of Lactobacilli and Escherichia coli, changes that could be related to small intestine dysfunction (7). Qualitative and quantitative changes in gut flora have been described in patients with IBS. A study of fecal samples has shown qualitative differences between healthy controls and IBS patients and between IBS patients with constipation or diarrhea predominant. The study showed that although patients with constipation-predominant IBS had higher concentrations of Veillonella spp, patients with diarrhea-predominant IBS had lower levels of Lactobacillus spp. Galatola et al found evidence of bacterial overgrowth in 56% diarrhea-predominant IBS and 28% of the constipation-predominant type (9). Pimentel et al have found bacterial overgrowth in 78% of patients with IBS (10). Changes in gut flora, resulting from the use of antibiotics, have also been proposed as a pathogenic mechanism of IBS. Studies have shown that patients who received antibiotics in the previous months were approximately 3 times more likely than patients who did not receive antibiotics to develop functional symptoms (11,12). Probiotics and antibiotics have also been used to treat a proposed dysfunctional relation between the indigenous flora and the host in patients with IBS (10,13–15). Verdu et al suggest a possible pathogenic mechanism linking changes in flora and IBS (16). Perturbations in gut flora and inflammatory cell activity may modify the sensory neurotransmitter content in the colon, leading to altered visceral perception, dysmotility, increased gas production, and changes in bowel habits. Increased numbers of inflammatory cells in the lamina propria, proximity of mast cells to nerves, and production of substances that activate receptors involved in visceral sensation have been shown in patients with IBS (17).
Pathogenic bacteria leading to acute gastroenteritis may also cause persistent GI symptoms and FGIDs including IBS (18) and dyspepsia (19). Postinfectious IBS develops in 10% to 34% of adult patients following acute infectious enteritis (20). A multicenter controlled study conducted by our group has recently demonstrated the presence of postinfectious IBS in children (21). This study showed a significant increase in prevalence of abdominal pain in patients experiencing acute gastroenteritis of bacterial origin several years after the initial episode subsided. Although the pathogenesis of postinfectious IBS remains unclear, some authors propose that changes in gut mucosal function and structure, increased mucosal permeability, infiltration of enteroendocrine cells, and persistent neuroimmune interactions leading to continuing sensorimotor dysfunction could explain this phenomenon (22).
The different organ systems also live in an integrated equilibrium with each other. The enteric nervous system has a bidirectional dialogue with the brain via parasympathetic and sympathetic pathways that integrate the brain–gut axis. Stress, defined as an acute threat to homeostasis, may lead to intestinal inflammation, increased intestinal permeability, visceral hypersensitivity, and dysmotility (23). Psychological and physical stressors may be involved in the onset and modulation of IBS symptoms. Stress can lead to mast cell activation, degranulation (24), and release of mediators that alter the gut motor response and visceral perception through its effect on enteric neurons and smooth muscle cells. Mast cells may constitute the final pathway of various mechanisms sensitizing the GI tract such as stress, food allergies, and infections (25). School-related stress may play a role in explaining the seasonal variation of abdominal pain and other somatic complaints described in healthy children at the community level and in consultations for abdominal pain (26). Three independent pediatric studies conducted in different settings have concluded that there is a higher prevalence of complaints and consultations for abdominal pain during winter months in comparison with summer months (26–28). However, the analysis of the monthly pattern of gastrointestinal complaints in different schools and cities showed that those complaints do not occur during the whole school year, whereas school-related stress should be present during the entire academic year. The presence of a significant decrease in somatic complaints at the end of winter and beginning of spring suggests a possible involvement of factors other than school stress. Minor or subclinical infections in certain months of the year could play a role in this seasonal pattern. A decreased ability to cope was described in children with recurrent abdominal pain (29). A study suggested different seasonal patterns of abdominal pain in children living in different latitudes (30). Limitations in outside activities due to weather conditions may result in a decreased ability to cope through play during certain months of the year.
The possible effect of hormones with an important environmental underpinning should also be considered. Melatonin production illustrates the integration between ecosystems and organ systems. Melatonin, initially thought to be found only in the pineal gland, was then shown to be present in a much greater concentration in the gut, mainly in the enterochromaffin cells. Melatonin serum levels vary according to the daylight cycle and weather (external ecosystem). Melatonin is also produced by the gut flora and its intestinal concentration is modulated by meals (internal ecosystem). Multiple studies have shown an important effect of melatonin on gastrointestinal function (31). Melatonin affects GI circadian entrainment, has antioxidant and cytoprotective activity, and anti-inflammatory effects. Melatonin also regulates gut motility and sensation, important factors in the pathogenesis of IBS (32). Multiple clinical trials have shown a beneficial role of melatonin in the treatment of IBS (33) and dyspepsia even in the absence of sleep disturbances (34). Melatonin has also been implicated in the treatment and pathogenesis of headaches (35), a common comorbidity in children with abdominal pain (36). Headaches and IBS share the biopsychosocial model (36). The evidence derived from these studies, the physiological implications of melatonin on the GI tract, and the presence of feedback mechanism between melatonin and serotonin justifies further investigation on the effects of this hormone on the GI tract and its possible role in the treatment of FGIDs (33,37).
In summary, health, illness, and the various phenotypic expressions of each condition may be viewed as the results of multiple internal and external factors interacting and mutually affecting each other. We should be open to explore novel factors that could advance our understanding of the pathogenesis of FGIDs.
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