Reference: September 2025 | Issue 9 | Vol 11 | Page 46
Multiple identifiable organic causes may be responsible for gastrointestinal (GI) tract symptoms, including cancer, inflammatory bowel disease, coeliac disease, peptic ulcer, and disorders of gut motility. For a substantial proportion of patients, however, investigations into the origin of these symptoms do not uncover any specific cause or abnormality. In these cases, symptoms are often referred to as ‘functional’.1
Functional GI disorders (FGIDs) can affect any part of the GI tract. Irritable bowel syndrome, functional dyspepsia, and constipation are the most common. By definition, FGIDs are not linked to any identifiable structural, morphological, or biochemical abnormality, with no biomarkers or imaging findings that can be of assistance in diagnosis.2
Because of this ambiguity, there is a risk of these disorders being thought of as purely psychogenic and being minimised, despite the significant prevalence and impact. FGIDs are associated with disruption to work performance, reduced quality of life, psychological comorbidities, and increased healthcare costs.
These conditions are increasingly considered to be disorders of gut-brain interaction, which more accurately reflects their scientific basis, and moves away from the stigma associated with the unclear pathophysiology and the term functional.
In cases where patients and healthcare professionals have considered these disorders to be purely psychological or of little importance, this has often been damaging, physically and emotionally. Due to the fear of being seen as having a psychological disorder, often patients avoid seeking medical intervention and, as a result, their condition is not managed appropriately.
Conversely, other patients increase their engagement with healthcare services, seeking a diagnosis that is perceived to be more acceptable.1
The Rome Foundation has created evidence-based methods to diagnose and classify FGIDs. There are 33 defined FGIDs in adults, categorised by anatomical location, and defined by a particular cluster of symptoms. Some of the more common FGID diagnoses and appropriate diagnostic tests are presented in Table 1.
The most recent Rome Foundation classification (Rome IV, 2016), advocated for these conditions to be thought of as disorders of gut-brain interaction, and for the acknowledgment of intricate interactions between contributing biological and psychosocial factors.
Treatments for FGIDs target management of both GI and psychological symptoms, rather than focusing on specific underlying disease mechanisms, once a clear organic pathology has been ruled out.
About 50 per cent of people in the Western world meet the criteria for a FGID at any given time. Up to a third of patients will have had potentially unnecessary surgery for the condition, eg, hysterectomy, cholecystectomy.3
FGIDs in Ireland
One study in Ireland collected data from a gastroenterology clinic with a special interest in FGIDs to ascertain the level and type of FGIDs most frequently encountered in this country.2 In the cohort of 2,231 patients included in the study, 41 per cent were diagnosed with an FGID using the Rome III diagnostic criteria. Table 2 shows the breakdown of this 41 per cent into different diagnoses.
Three in five (60 per cent) FGID patients presenting at the gastroenterology clinic already had diagnoses of organic GI disorders such as gastro-oesophageal reflux disease, Helicobacter pylori infection, gastritis, duodenitis, and hiatus hernia. Just over a third (36 per cent) of these were referred to other specialists.
The distinctions between various FGIDs can be unclear and many patients may present with symptoms attributable to more than one FGID.2 Women appeared to present more often and with a more classical appearance of FGID (somatic symptoms, fatigue, stress, anxiety as a precipitant). This may explain partially why, in general, women are diagnosed more readily than men.
There are significant overlaps between the occurrence of FGIDs and other disorders like fibromyalgia, atypical migraine, depression and anxiety, chronic low back pain, and chronic pelvic pain. Potentially, an increase in health-seeking behaviour may increase the likelihood in diagnosing these comorbid conditions in this population, however, there may be alternative explanations.
Visceral hypersensitivity, abnormal GI motility, and psychological disturbances have all been recognised to contribute to the origin of FGIDs for many years. But, more recently, low-grade intestinal inflammation, increased intestinal permeability, immune activation, and disturbances in the microbiome have also been identified as important contributing factors.
Low-grade inflammation and disturbances in the gut microbiome are known to have a greater impact on health status, including the pathogenesis of these comorbid conditions, than previously accepted.1
| DISORDER | DEFINITION | TESTS REQUIRED |
|---|---|---|
| Functional dysphagia | Sensation of abnormal food bolus transit through the oesophagus, no abnormalities present (structural, motor, or mucosal) | Includes endoscopy, biopsies, barium swallow (radiology) |
| Functional heartburn | Retrosternal burning/pain/discomfort refractory to acid suppression therapy. No reflux or abnormalities present | Includes endoscopy, biopsies |
| Functional chest pain | Recurrent, unexplained retrosternal chest pain, presumably of oesophageal origin. Different to heartburn and not explained by any abnormality | Includes cardiology assessment, endoscopy, biopsies |
| Functional dyspepsia | One or more symptoms of postprandial fullness, early satiety, epigastric pain/burning that are unexplained after investigation | Endoscopy, biopsies if alarm bells are present |
| IBS | Recurrent abdominal pain, at least one day a week, linked with defecation/change in bowel habits | Includes FBC, CRP, coeliac serology |
| Functional constipation | Difficult, infrequent or incomplete defecation, not meeting criteria for IBS; abdominal pain might be present, but not predominant | Includes FBC, TFTs, serum calcium |
| Functional abdominal bloating and distension | Abdominal fullness, pressure, or trapped gas (bloating) sensations, along with measurable distension, which does not meet the criteria for another disorder | Includes FBC, coeliac serology |
| Rumination syndrome | Repetitive, effortless regurgitation of recently ingested food into the mouth, followed by re-chewing and re-swallowing, or expulsion | High-resolution oesophageal manometry |
| FGID undefined/unknown | Bowel symptoms, not attributable to an organic cause, not meeting diagnostic criteria for other FGIDs | Investigations as specified for IBS, functional constipation, functional abdominal bloating |
TABLE 1: Definitions of some of the most common Rome IV FGIDs and confirmatory tests required1
| FGID DIAGNOSIS | PER CENT |
|---|---|
| IBS | 41 |
| Functional constipation | 22.5 |
| Functional dyspepsia | 21 |
| Functional bloating | 8.2 |
| Functional abdominal pain syndrome | 7.9 |
| Rumination syndrome | 6.4 |
| Aerophagia | 6 |
| FGID undefined/unknown | 5.6 |
| Functional heartburn | 5.6 |
TABLE 2: Percentages of various FGID diagnoses in an Irish sample.2
The microbiome
The gut microbiome is the collective genomes of the micro-organisms in the GI environment. A community of 100 trillion micro-organisms are present in the human GI tract.4 These gut microbiota perform essential functions, including the fermentation of non-digestible substances like fibre and endogenous mucus.
Fermentation in turn encourages the growth of microbes responsible for producing short chain fatty acids (SCFAs) ie, butyrate, acetate, and propionate, which play a role in glucose regulation and metabolism through multiple mechanisms and gases.
Butyrate is the main source of energy for colonocytes. It contributes to glucose and energy homeostasis and prevents gut dysbiosis. Propionate travels to the liver to regulate gluconeogenesis and satiety signalling.
Acetate, the most common SCFA, promotes bacterial growth in the gut and also plays a role in central appetite regulation when it reaches the periphery. Lower levels of gut microbiota diversity have been associated with conditions like obesity, inflammatory bowel disease, psoriatic arthritis, type 1 and 2 diabetes, atopic eczema, coeliac disease, and arterial stiffness. A diverse gut ecosystem appears to be more robust against environmental influences.
Diet
Certain dietary products have negative effects on this gut diversity, such as food additives (emulsifiers) and the artificial sweeteners sucralose, aspartame, and saccharin. Medication can also have a significant impact on the composition of gut microbiota. Osmotic laxatives, progesterone, TNF alpha inhibitors, proton pump inhibitors, and antibiotics have all been shown to impact the gut microbiome.4 Additionally, the microbiota can influence individual response to chemotherapy and immunotherapy.
Supplementation with probiotics (live bacteria and yeasts) has several beneficial effects. Prebiotics, also beneficial, are composed of substrates that are used selectively by micro-organisms (ie, microbiota-accessible carbohydrates, fermentable dietary fibre) that confer a health benefit.
Synbiotics are a mix of both prebiotics and probiotics. Sufficient fibre intake is vital for gut health. In cases of low-fibre diets, as is common in the Western world, there is evidence that the colonic mucus barrier can be damaged, resulting in pathogen susceptibility and inflammation. This is a mechanism for chronic disease pathogenesis.
Probiotics (mostly Bifidobacterium and Lactobacillus species) are included in a variety of foods and dietary supplements and their therapeutic effect has been broadly studied. Although it has been suggested that the microbes in many probiotic supplements are not able to establish themselves sufficiently in the gut to exert a meaningful effect, they can also impact health through additional mechanisms, such as immune modulation, or the production of bioactive compounds.4
There is evidence for the beneficial effects of probiotic supplementation for a wide range of indications including prevention of diarrhoea, necrotising enterocolitis, acute respiratory tract infections, pulmonary exacerbations in children with cystic fibrosis, and eczema in children. They also improve cardiometabolic parameters and C-reactive protein in patients with type 2 diabetes.
Unfortunately, due to the heterogeneity of research studies to date in terms of type of probiotic, length of treatment period, and range of conditions studied, it is difficult to make any specific recommendations in terms of probiotic regimens.
A health indicator
A new tool called the Gut Microbiome Wellness Index 25 has been developed. This tool is able to identify changes in gut health that occur before serious symptoms arise, with the aim of enabling a proactive response through dietary and lifestyle changes to prevent the development of poor health, ie, an early warning system. Early detection of gut imbalances can offer the opportunity to enhance wellness and prevent disease.6
Data from publicly available stool metagenome samples provided by both healthy (n=5547) and non-healthy people (n=2522) were used to create the dataset.5 The tool demonstrates over 80 per cent accuracy in distinguishing between healthy individuals and those with diseases, providing a standardised index to quantitatively measure how healthy a person’s gut is.
The creators of this tool intend to develop it further using artificial intelligence techniques to improve its accuracy and broaden its dataset to include even more diverse samples of healthy and unhealthy populations. This is a great opportunity to use information from the gut to not only inform about digestive issues and gut health but, in a much broader way, to decipher and identify more complex disease states.
References
- Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: Advances in understanding and management. Lancet. 2020;396(10263):1664-74.
- Walsh K, McWilliams SR, Maher MM, Quigley EM. The spectrum of functional gastrointestinal disorders in a tertiary referral clinic in Ireland. Ir J Med Sci. 2012;181:81-6.
- Aziz I, Palsson OS, Tornblom H, Sperber AD, Whitehead WE, Simren M. The prevalence and impact of overlapping Rome IV diagnosed functional gastrointestinal disorders on somatisation, quality of life, and healthcare utilisation: A cross-sectional general population study in three countries. Am J Gastroenterol. 2018;113:86-96.
- Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:k2179.
- Chang D, Gupta VK, Hur B, Cobo-López S, Cunningham KY, Han NS, et al. Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles. Nat Commun. 2024;15(1):7447.
- Putol R. New tool detects changes in gut health to help prevent disease [Internet]. Earth.com; 2024 Sep 7. Available at: www.earth.com/news/new-tool-detects-changes-in-gut-health-to-help-prevent-disease/.
