Gastric sensorimotor dysfunction

The gastrointestinal tract utilises sophisticated networks of receptors and signalling pathways to detect and respond to nutrients via three primary sensory modalities: chemosensitivity (nutrient composition), thermosensitivity (temperature) and mechanosensitivity (pressure and distension)^{(Reference Farré and Tack29)}. Gastric sensing of food is primarily mediated by mechanosensitive pathways that signal to the brain via vagal afferent nerves, with this process modulated by the gastric accommodation reflex^{(Reference Janssen, Vanden Berghe and Verschueren30–Reference Janssen, Verschueren and Tack32)}.

In the small intestine, specialised chemosensors detect changes in pH, osmolarity and nutrient composition^{(Reference Farré and Tack29)}, triggering the release of gut peptide hormones such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)^{(Reference Farré and Tack29,Reference Houte, Bercik and Simren33)} . These hormones influence gastric emptying, appetite regulation and energy intake through both local and systemic effects^{(Reference Farré and Tack29)}.

FD is associated with alterations in these sensory processes. Visceral hypersensitivity – an exaggerated response to normal physiological stimuli – is a key pathophysiological feature of FD, particularly sensitivity to chemical and mechanical stimuli which has been associated with weight loss, belching and epigastric pain^{(Reference Enck, Azpiroz and Boeckxstaens17,Reference Farré and Tack29,Reference Feinle, Meier and Otto34–Reference Lee, Vos and Janssens38)} . Impaired gastric accommodation correlates with reduced drinking capacity, early satiety, postprandial fullness and weight loss^{(Reference Tack, Caenepeel and Piessevaux39–Reference Tack, Janssen and Masaoka42)}, while delayed gastric emptying more commonly presents with nausea, vomiting, postprandial fullness and early satiety^{(Reference Stanghellini, De Giorgio and Barbara43,Reference Sarnelli, Caenepeel and Geypens44)} . However, the correlation between delayed gastric emptying and FD symptoms remains inconsistent^{(Reference Carbone, De Buysscher and Van den Houte45)}. These disturbances in gastric sensorimotor function serve as key targets for treatment strategies showing beneficial symptomatic effects when addressed^{(Reference Tack, Demedts and Meulemans41,Reference Vijayvargiya, Jameie-Oskooei and Camilleri46–Reference Carbone, Van den Houte and Clevers48)} .

Duodenal inflammation and microbiota dysbiosis

Low-grade mucosal inflammation, characterised by increased eosinophils and mast cells has emerged as a significant pathophysiological mechanism in FD^{(Reference Du, Chen and Kim49)}. The activation of these inflammatory cells leads to the release of pro-inflammatory cytokines, resulting in tissue damage, disrupted epithelial barriers and altered enteric nerve function^{(Reference Walker, Warwick and Ung50)}. This process increases epithelial permeability, potentially allowing greater infiltration of luminal antigens and amplifying immune responses^{(Reference Ford, Mahadeva and Carbone2)}. Recent evidence points to small intestinal microbial dysbiosis as a potential contributor to FD pathophysiology^{(Reference Zhong, Shanahan and Raj51–Reference Cervantes, Michael and Hong53)}. Studies have identified significant alterations in duodenal mucosal microbial composition in FD patients, including increased abundance of Streptococcus spp. and decreased anaerobic genera such as Prevotella^{(Reference Saffouri, Shields-Cutler and Chen52,Reference Cervantes, Michael and Hong53)} . Importantly, duodenal bacterial load has been negatively correlated with quality of life and positively associated with symptom severity in FD patients^{(Reference Zhong, Shanahan and Raj51)}. Symptoms including pain, nausea and epigastric discomfort, as well as impaired gastric emptying, have been correlated with elevated levels of small bowel-homing T cells and pro-inflammatory cytokine, suggesting that motor dysfunction may be secondary to duodenal inflammation and microbial alterations^{(Reference Liebregts, Adam and Bredack54,Reference Kindt, Tertychnyy and De Hertogh55)} .

Ford et al. propose that physiological or psychological insults can lead to loss of tolerance to previously tolerated food antigens, enabling interaction between microbiota, food antigens and the immune system, resulting in localised inflammatory responses^{(Reference Ford, Staudacher and Talley56)}. Supporting this, recent studies have identified small intestinal dysbiosis associated with both the development and occurrence of FD^{(Reference Zhong, Shanahan and Raj51,Reference Saffouri, Shields-Cutler and Chen57–Reference Trakman, Fehily and Basnayake60)} .

Gut–brain axis dysregulation

Dysfunction of the gut–brain axis plays an important role in FD pathophysiology. Psychological factors, particularly stress, exacerbate symptoms in many FD patients, with up to 50% identifying stress as a clear symptom trigger^{(Reference Piessevaux, De Winter and Louis61)}. Studies demonstrate that stress, through corticotrophin-releasing hormone release, can significantly impact gastrointestinal function by increasing epithelial permeability and altering immune function^{(Reference Vanuytsel, Bercik and Boeckxstaens62,Reference Vanuytsel, Sv and Vanheel63)} . Notably, anxiety has been associated with duodenal eosinophilia in FD, highlighting the interplay between psychological stress and immune activation^{(Reference Ronkainen, Aro and Walker64)}.

Neuroimaging studies have identified structural and functional alterations in brain regions involved in the processing of visceral input^{(Reference Liu, Fan and Wei65,Reference Chen, Wang and Hou66)} . These findings support bidirectional gut–brain alterations in FD, where overactive visceral signalling from the gut may heighten symptom perception, while central sensitisation may amplify symptom severity.

These interacting pathophysiological mechanisms – sensorimotor dysfunction, duodenal inflammation, microbial dysbiosis and altered gut–brain signaling – create multiple potential targets for dietary intervention in FD management.

Lipids: primary triggers of symptoms in FD

FD patients frequently report sensitivity to high-fat foods, and a systematic review examining the relationship between food and FD found dietary fats to be consistently associated with PDS symptoms^{(Reference Duncanson, Talley and Walker67)}. Barbera et al. validated the nutrient-specific effects of lipids in FD in a cohort of 18 dyspeptic patients and 9 healthy subjects. Their study demonstrated that isocaloric duodenal glucose infusion did not produce the same symptomatic response of epigastric fullness and discomfort as lipid infusion during gastric distension in FD patients. Healthy controls experienced no symptoms in response to either duodenal glucose or lipid infusions^{(Reference Barbera, Feinle and Read68)}. The same group later demonstrated that duodenal lipid infusion increased gastric sensitivity to distension in FD patients, provoking symptoms of nausea and epigastric bloating absent in healthy controls^{(Reference Barbera, Feinle and Read69)}. Both studies reported no differences in gastric motor response between healthy controls and FD patients during distension, suggesting that FD symptoms may stem from visceral hypersensitivity^{(Reference Barbera, Feinle and Read69)}. Interestingly, while duodenal lipid infusion heightened gastric sensitivity to distention in FD patients, it had the opposite effect in healthy controls and induced gastric relaxation – potentially an adaptive response to accommodate greater volumes of nutrient-dense food^{(Reference Barbera, Feinle and Read68,Reference Barbera, Feinle and Read69)} .

Feinle et al. found duodenal lipid infusion induced dyspeptic symptoms of fullness, epigastric discomfort and nausea in response to gastric distension^{(Reference Feinle, Meier and Otto34)}. The study additionally demonstrated that symptoms experienced by FD patients during lipid infusion and gastric distension were significantly alleviated by CCK-A receptor antagonist dexloxiglumide, thus confirming the likely involvement of CCK-A receptors in mediating lipid-induced dyspeptic symptoms^{(Reference Feinle, Meier and Otto34)}. Bharucha et al. confirmed this association between plasma CCK levels and symptom severity (nausea, fulness and bloating) during lipid infusion^{(Reference Bharucha, Camilleri and Burton70)}. The increase in CCK observed in both healthy controls and FD patients suggests that hypersensitivity to normal CCK levels, rather than excessive CCK secretion, underpins the pathophysiological involvement of CCK in FD symptom generation^{(Reference Feinle, Meier and Otto34,Reference Bharucha, Camilleri and Burton70)} . Notably, both studies demonstrated exacerbations in FD symptoms during lipid infusion even in the absence of gastric distensions, thus implicating chemosensitivity as a potential mechanism in the pathophysiological response to lipids^{(Reference Feinle, Meier and Otto34,Reference Bharucha, Camilleri and Burton70)} . A single study has evaluated the relationship between increasing doses of duodenal lipid infusion, plasma CCK levels and symptom severity in FD. Using 10% and 20% Intralipid infusions, the study demonstrated a clear dose-dependent relationship where higher lipid doses were associated with increased plasma CCK concentrations and intensified symptoms of fullness, epigastric discomfort and nausea^{(Reference Feinle, Meier and Otto34)}. The release of CCK contributes to symptom generation in FD through multiple mechanisms: (1) direct activation of vagal afferents by carrying sensory information to the brain, (2) increased sensitivity of gastric mechanoreceptors to distension, (3) increased chemosensitivity to presence of duodenal lipid (4) reduced gastric motility and (5) delayed gastric emptying^{(Reference Pilichiewicz, Feltrin and Horowitz21,Reference Feinle, Meier and Otto34,Reference Bharucha, Camilleri and Burton70,Reference Fried and Feinle71)} . These effects are exaggerated in FD patients compared to healthy controls, suggesting hypersensitivity to normal physiological CCK responses rather than excessive CCK production.

While duodenal infusion studies provide valuable mechanistic insights into the role of lipids in FD, they do not replicate normal eating conditions. These studies bypass normal digestive processes, are invasive, and often involve unnaturally high lipid concentrations. Yet, these mechanistic findings are supported by diet studies comparing high versus low-fat meals. A high-fat meal, simulated by adding 30 g of margarine to soup, elicited greater symptomatic response (epigastric pain and nausea) in FD patients compared to a low-fat soup without added fat^{(Reference Houghton, Mangall and Dwivedi72)}. Furthermore, a high-fat yoghurt (24 g fat, 330 kcal) significantly increased symptoms of fullness, bloating and nausea compared with low-fat yoghurt (1 g fat, 143 kcal) in FD patients^{(Reference Feinle-Bisset, Meier and Fried73)}. Both studies may be confounded by differences in caloric content. However, Pilichiewicz et al. addressed this limitation by utilising equicaloric high-fat and high-carbohydrate meals (400 g yoghurt). Their findings demonstrated significantly greater FD symptoms, particularly nausea and pain, with the high-fat meal (32 g fat, 500 kcal) compared to the isocaloric high-carbohydrate meal (6 g fat, 500 kcal), confirming the involvement of dietary fats in symptom generation^{(Reference Pilichiewicz, Feltrin and Horowitz21)}. Table 1 provides a summary of the key infusion and dietary challenge studies investigating nutrient-symptom relationships in FD.

Table 1. Summary of infusion and dietary challenge studies in adults with functional dyspepsia

CCK, cholecystokinin; CHO, carbohydrates; FD, functional dyspepsia; FODMAP, fermentable oligosaccharides, disaccharides, monosaccharides and polyols; HC, healthy controls; NDI, Nepean Dyspepsia Index; PYY, peptide YY; QoL, quality of life; RCT, randomised controlled trial; SAGIS, Structured Assessment of Gastrointestinal Symptoms; SDA, standard dietary advice; SF-NDI, Short Form Nepean Dyspepsia Index.

Limited research has examined the specific effects of different fat types on FD symptoms. Existing duodenal infusion studies have consistently utilised Intralipid – a soyabean oil formulation naturally high in polyunsaturated fats – while dietary intervention studies have typically increased fat content using cream, rich in saturated fats. Given all studies reported a positive association between fat consumption and dyspeptic symptoms such as nausea, pain, epigastric fulness, bloating and discomfort, various fat types may contribute to symptom generation in FD. Although current dietary intervention trials have some limitations, such as the use of semi-solid or liquid-based meals that may not reflect typical real-world eating patterns, they nonetheless provide valuable insights. Overall, the current evidence from both nutrient infusion and dietary intervention trials consistently demonstrates that dietary lipids are potent triggers of FD symptoms, likely through CCK-mediated pathways and heightened visceral sensitivity.

Fermentable carbohydrates

FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are short-chain carbohydrates poorly absorbed in the small intestine. Upon reaching the colon, they are fermented by gut bacteria, leading to gas production and luminal distention. FODMAP are found in various foods including fruits, vegetables, grains, dairy products, legumes and sweeteners. The low FODMAP diet has substantial research demonstrating efficacy in reducing IBS symptoms and is widely utilised as first-line dietary therapy^{(Reference Black, Staudacher and Ford74)}. Although the impact of FODMAPs on gastric motility in FD has not been directly studied, evidence from IBS and healthy controls indicates that FODMAPs may affect upper GI function. One study found that acute intragastric fructan infusion increased postprandial intragastric pressure in both IBS patients and healthy individuals^{(Reference Masuy, Van Oudenhove and Tack75)}. Symptoms developed rapidly – within 30 minutes – suggesting involvement of the proximal small intestine in FODMAP-induced symptom generation^{(Reference Masuy, Van Oudenhove and Tack75)}. Given the frequent clinical overlap between IBS and FD and their shared pathophysiological features, the low FODMAP diet may also alleviate symptoms in at least a subgroup of FD patients. A systematic review identified that foods frequently associated as FD symptom triggers were also high in FODMAPs (e.g. wheat/grain products, some soft drinks, fruit/fruit juice, milk)^{(Reference Duncanson, Talley and Walker67)}. Supporting this, a recent cross-sectional study by Cooke et al. found 55% of dyspepsia patients identified FODMAPs as symptom triggers^{(Reference Cooke, Resciniti and Wright76)}.

In an early study, Wilder-Smith et al. screened 1372 patients with various DGBI, including 606 with FD, for both lactose and fructose malabsorption and intolerance^{(Reference Wilder-Smith, Materna and Wermelinger77)}. Of those testing positive, 312 participants undertook a 4-week dietary intervention, beginning with saccharide and polyol restriction, followed by systematic reintroduction of defined doses of fructose, fructan, inulin and lactose to assess individual tolerance. Although fructose and lactose intolerance tests lack sensitivity^{(Reference Gasbarrini, Corazza and Gasbarrini78)}, over 80% achieved substantial symptom relief following dietary restriction of saccharides and polyols^{(Reference Wilder-Smith, Materna and Wermelinger77)}. Subsequent studies focusing specifically on FD have yielded encouraging results. Potter et al. conducted a pilot double-blind, randomised, placebo-controlled trial investigating effects of a four-week gluten-free and low FODMAP diet in nine FD patients. The intervention showed modest, non-significant symptom improvement. Four participants met the response threshold for rechallenge with muesli bars containing fructan, gluten or placebo, but no specific food trigger could be reliably identified^{(Reference Potter, Duncanson and Jones79)}. The study’s robust design was limited by its small sample size and combined dietary approach, preventing definitive conclusions about specific dietary components in FD. Staudacher et al. conducted an observational study comparing low FODMAP diet to standard dietary advice (SDA) in FD patients^{(Reference Staudacher, Nevin and Duff80)}. The SDA consisted of recommendations to reduce caffeine, alcohol, fat, fibre, or healthy eating advice based on the Australian Dietary Guidelines. Participants on the low FODMAP diet experienced greater reduction in epigastric scores for symptoms of postprandial pain, bloating and belching than those on SDA. Notably, 81% of participants had co-existing IBS, potentially confounding results. In a preliminary report, 25 FD patients followed a 6-week low FODMAP diet and subsequently underwent blinded reintroduction of FODMAP powders to determine individual triggers. Over half experienced improvements in fullness, satiation and upper abdominal bloating while on the low FODMAP diet, with mannitol and galacto-oligosaccharides most identified as symptom triggers^{(Reference Houte, Carbone and Toth81,Reference Rettura, Lambiase and Grosso82)} . The study additionally showed that the low FODMAP diet was associated with improved duodenal mucosal integrity. Goyal et al. further explored this in a prospective, single-blind trial comparing low FODMAP and SDA in 105 FD patients over 4 weeks, followed by guided FODMAP reintroduction for the low FODMAP group^{(Reference Goyal, Nohria and Batta83)}. No significant difference in overall symptom improvement was observed between groups, with both achieving symptom relief and improved quality of life. However, patients with PDS subtype or bloating responded significantly better to the low FODMAP diet.

Several mechanisms may explain how FODMAPs elicit symptoms in FD. First, FODMAPs exert osmotic effects in the small intestine drawing water into the lumen as demonstrated by MRI studies in healthy controls and IBS patients^{(Reference Murray, Wilkinson-Smith and Hoad84–Reference Marciani, Cox and Hoad86)}. This luminal distension may activate small intestinal mechanoreceptors in viscerally hypersensitive FD patients, generating symptoms well before colonic fermentation occurs. Second, rapid fermentation of FODMAPs produce gas and SCFA^{(Reference Piche, des Varannes and Sacher-Huvelin87)} that directly stimulate chemosensitive pathways in the proximal gut. Third, FODMAPs may influence gut microbiota composition and mucosal immune function, as suggested by preliminary data showing the low FODMAP diet improves duodenal mucosal integrity in FD patients^{(Reference Houte, Carbone and Toth81)}. Finally, colonic fermentation of FODMAPs may trigger gastro-colonic reflexes that alter proximal gastrointestinal motility and sensitivity^{(Reference Piche, des Varannes and Sacher-Huvelin87)}. Current evidence suggests that FODMAP restriction may be particularly beneficial for patients with PDS subtype FD, especially those experiencing bloating or with concurrent IBS symptoms. The identification of specific FODMAP triggers through systematic reintroduction may allow for personalised dietary modifications rather than long-term global FODMAP restriction. Beyond macronutrients, other dietary factors and bioactive components may also contribute to FD symptom generation.

Additional dietary triggers and modifiers

The gastrointestinal tract is exposed to various naturally occurring or synthetic bioactive substances. Food chemicals such as salicylates, amines, glutamates and lectins, found in many plant and animal-based foods, have also been suggested to influence gastrointestinal function^{(Reference Cooke, Lynam and Tuck88)}. While a diet low in food chemicals has been shown to benefit patients with IBS, their potential to induce symptoms has not been specifically studied in the FD population, nor has its therapeutic potential^{(Reference Gibson, Varney and Malakar89)}. In addition to naturally occurring substances – compounds introduced during food processing to improve appearance, texture, shelf life, or nutritional value – represent another potential trigger. A large-scale web-based cohort study identified that increased proportion of ultra-processed foods was associated with higher risk of FD with concomitant IBS, though not FD in isolation^{(Reference Schnabel, Buscail and Sabate90)}. This may suggest a potential association between food additives and FD occurrence, particularly in overlapping syndromes.

Certain commonly consumed beverages, such as coffee and alcohol, have also been investigated for their role in FD symptoms. Coffee consumption has been linked to increased gastric acid secretion and associated with induction of FD symptoms across several studies^{(Reference Duncanson, Talley and Walker67,Reference Elta, Behler and Colturi91–Reference Kaess94)} . However, evidence remains inconclusive; one study specifically investigating coffee intake effects in FD patients found no significant association between consumption and symptom exacerbation^{(Reference Talley, McNeil and Piper95)}. The inconsistency in findings suggests individual variation in response to caffeine that warrants personalised assessment. Alcohol increases gastric acid secretion and influences gastric emptying rates^{(Reference Bujanda96)}, potentially contributing to FD symptoms. Some studies report a positive association between alcohol consumption and both development and worsening of FD symptoms. However, findings have been inconsistent, and no definitive relationship has been established^{(Reference Talley, McNeil and Piper95,Reference Talley, Weaver and Zinsmeister97,Reference Halder, Locke and Schleck98)} . As with coffee, the effects of alcohol may vary significantly between individuals, highlighting the importance of personalised dietary assessment.

Several bioactive plant compounds directly affect sensory receptors in the gastrointestinal tract^{(Reference Liu, Asif and Bai99)}. Capsaicin from red pepper may modulate symptoms through TRPV1 receptor stimulation, showing potential to reduce pain, fullness and nausea in FD patients^{(Reference Bortolotti, Coccia and Grossi100)}. Menthol from Mentha species acts on TRPM8 channels, potentially reducing abdominal pain and improving quality of life^{(Reference Khonche, Fallah Huseini and Abdi101)}. Ginger compounds, particularly 6-gingerol and 6-shogaol, may alleviate FD symptoms through thermosensitive and mechanosensitive pathways^{(Reference Aregawi, Shokrolahi and Gebremeskel102)}. However, evidence for these compounds comes mainly from small trials or supplement studies rather than typical dietary interventions.

Research priorities

Current evidence provides a foundation for understanding diet–FD relationships, but significant knowledge gaps remain. Although dietetic management of FD commonly involves trial of a low-fat diet, evidence is limited regarding optimal restriction levels, differential effects of fat types and symptom-specific responses. Future studies should determine whether certain fatty acids are more symptom-provoking than others. For FODMAPs, research should focus on identifying specific FODMAP subgroups that trigger symptoms, assessing variations in FODMAP sensitivity across FD subtypes, and determining symptom patterns most associated with FODMAP intolerance. Additionally, further investigation is needed to determine whether dietary interventions address underlying pathophysiological mechanisms, such as low-grade inflammation and alterations in the gut microbiome, or primarily alleviate symptoms without addressing root causes. Methodological improvements in FD dietary research are essential. Development of validated FD-specific dietary assessment tools would enhance research quality and enable more reliable cross-study comparisons. Longer-term studies are needed to assess sustained efficacy, adherence challenges and nutritional adequacy of dietary modifications.

Clinical practice recommendations