Disorders of the brain-gut interaction and eating disorders

Table 1 Studies investigating the association between gastroparesis and eating disorders

Ref.	Aims	Study population	Assessment instruments	Results and conclusions
Szmukler et al[18], 1990	To determine the natural history of delayed gastric emptying of solid foods in AN	20 consecutive female inpatients. 8 restrictive AN. 10 AN and BN. 2BN. Mean age: 22.8 ± 5.2 yr. Duration of illness: 49.0 ± 37.4 mo	Scintigraphy; HET; BMI	HET > 110 min. HET significant negative correlation with BMI; delayed gastric emptying in AN improves quite rapidly as feeding recommences
Hutson and Wald[19], 1990	To measure: Gastric emptying of a mixed liquid and solid meal in patients with AN, BN, and HC; the relationship of body weight and gastrointestinal symptoms to gastric emptying	11 BN. 10 AN. A sex-matched HC	A dual radioisotope technique	Gastric emptying of solids in patients with BN was similar to that in HC (gastric T1/2 131 ± 15 min vs 119 ± 7 min; mean ± SEM). AN patients had overall delayed emptying (182 ± 31 min; P < 0.05); gastric emptying of liquids was similar in the BN and HC (gastric T1/2 48 ± 5 min and 49 ± 4 min, respectively), AN tended to have prolonged gastric emptying (65 ± 11 min, P = NS). There was no correlation between body weight, gastrointestinal symptoms, and gastric emptying
Benini et al[20], 2004	To compare dyspeptic symptoms and gastric emptying times. To examine the relationship between dyspeptic symptoms, gastric motility, behavioral and psychological features of eating disorders and general psychopathology. To study the effect of simple reefeding and of long-term rehabilitation on gastric symptoms and on parameters of psychopathological distress	23 AN. 12 binge/purging subtype. Mean age 19.9 ± 0.7 yr; mean BMI 13.2 ± 0.6, 11 restricting subtype; mean age 25.4 ± 1.1 yr; mean BMI 15.5 ± 0.7. 24 HC age and sex matched	Ultrasonographic gastric-emptying test, psychopathological questionnaires (SCL-90, EDI, EDE-Q). The bowel symptom questionnaires. VAS for hunger and epigastric fullness	Gastric symptom scores: Markedly higher in AN than in HC; improved significantly with treatment; no correlation between entry values of gastric emptying symptoms and questionnaire score was found; long-term rehabilitation improves gastrointestinal symptoms, gastric emptying and psychopathological distress in an independent manner, but not short-term refeeding
Inui et al[21], 1995	Analyzing gastrointestinal motility abnormalities in ED patients	26 female patients. 9 AN (mean age 22.5 ± 2.0 yr). 10 AN and BN (mean age 22.2 ± 1.6 yr). 7 BN (mean age 19.2 ± 1.2 yr). 9 HC	Gastric emptying: Radionuclide technique SDS; CAS	ED patients had delayed gastric emptying after ingestion of a solid meal. The patients has high depression and anxiety scores
Dubois et al[22], 1979	Measure of gastric emptying and gastric output concurrently in a group of patients with AN before and after weight gain	15 female AN age 14-32 yr; weight 34 ± 1 kg; 11 HC (8 male and 3 female) age 20-31 years old weight 68 ± 3 kg	Dye dilution technique; Barium meal x-ray examination	Fractional gastric emptying rate was significantly less in AN patients than in controls during basal conditions and following a water load, but not during maximal doses of pentagastrin. Emptying is inversely correlated with body weight in healthy controls. Gastric emptying is abnormally low in AN patients, even after weight gain
Kamal et al[23], 1991	To determine whether small bowel transit time or colonic transit time is delayed in AN and BN. To determine whether delays in gastrointestinal transit are correlated with symptoms of constipation or bloating	10 AN (9 female, 1 male). 18 BN (15 female, 3 male). 10 female HC	Whole-gut transit was tested by the radiopaque marker technique, mouth-to-cecum transit time was assessed by the lactulose breath test	Whole-gut transit time was significantly delayed in both AN (66.6 ± 29.6 h) and BN (70.2 ± 32.4 h) compared with HC (38.0 ± 19.6 h). Mouth-to-cecum transit time longer in AN (109.0 ± 33.5 min) and BN (106.2 ± 24.5 min) than in HC (84.0 ± 27.7 min), but these differences were not statistically significant
Robinson et al[24], 1988	Determinants of delayed gastric emptying in AN and BN patients	22 AN patients (21 female and 1 male). 10 BN female. 10 HC (8 female and 2 male)	Gamma camera technetium 99m-sulphur colloid	Only gastric emptying rates of the solid meal and glucose solution were significantly delayed. The gastric disturbance was confined to patients with AN patients selecting their own diet. Patients receiving adequate nutrition on the ward had normal gastric emptying and weight gain in this group had no significant effect on emptying. Slow emptying was observed in patients who maintained a low weight solely by food restriction as well as in patients whose AN was complicated by episodes of bulimia. Gastric emptying in BN was normal
Bluemel et al[26], 2017	Relationship of postprandial gastrointestinal motor and sensory function with body weight	24 AN [BMI 14.4 (11.9–16.0) kg/m2]. 16 OB [34.9 (29.6-41.5) kg/m2]. 20 HC [21.9 (18.9-24.9) kg/m2]	MRI and 13C-lactose-ureide breath test	Gastric half-emptying time (t50) was slower in AN than HC (P = 0.016) and OB (P = 0.007). A negative association between t50 and BMI was observed between BMI 12 and 25 kg/m2 (P = 0.0). Antral contractions and oro-cecal transit were not different. Self-reported postprandial fullness was greater in AN than in HC or OB (P < 0.001). After weight rehabilitation, t50 in AN tended to become shorter (P = 0.09) and postprandial fullness was less marked (P < 0.01)
Holt et al[27], 1981	Gastric emptying of the solid and liquid components of a physiological test meal	10 AN female patients, age 17-32 yr, mean weight 42 kg. 12 HC (6 females, 6 males, age 32-65 yr; mean weight 67 kg	Scintiscanning method	Significantly slower gastric emptying was found for both the liquid and the solid components of the meal in AN patients compared with HC. Emptying during the early phase (0-40 mm after meal ingestion) was not significantly differently in the two groups
Abell et al[28], 1987	Gastrointestinal and neurohormonal function measuring gastric electrical activity, antral phasic pressure activity, gastric emptying of solids and liquids, and hormonal and autonomic function in AN patients	8 AN (2 male and 6 female), age: 16-31 yr. 8 HC (2 male and 6 female) age19-34 yr	Gastric electrogastrography and manometry (fasting and postprandially), radioscintigraphic gastric emptying test, cold pressor test	AN patients: Increased episodes of gastric dysrhythmia (mean percentage of dysrhythmic time: 9.75 patients vs 0.48 controls during fasting, P < 0.02; 7.21 patients vs 0.18 controls postcibally, P < 0.001); impaired antral contractility (mean motility index, 12.8 patients vs 14.2 controls, P < 0.002); delayed emptying of solids; decreased postcibal blood levels of norepinephrine and neurotensin; impaired autonomic function
Rigaud et al[29], 1988	Effects of renutrition on gastric emptying in AN patients	14 AN inpatients (13 female and 1 male); duration of illness: 9 mo-40 yr; mediane 5.9 yr); age 18-61 yr	Double-isotope technique (111In) DTPA and 99mTc-ovalbumin	Gastric emptying can be improved by a renutrition program in AN
Waldholtz et al[30], 1990	To determine the type and frequency of gastrointestinal symptoms. To follow symptoms during refeeding prospectively. To develop guidelines for gastrointestinal testing and intervention in hospitalized AN patients	16 AN consecutive patients in their early 20 s, chronically ill (4.5 ± 1.2 yr); 71.6% ± 2.9% of matched population weight, 12 HC	AN patients rated on 12 gastrointestinal symptoms before and after nutritional rehabilitation. GISS (24 questions); blood tests physical examination	Belching did not improve during treatment. No patients required endoscopy, x-ray evaluation, or antipeptic regimens. Although severe gastrointestinal symptoms are common in AN, they improve significantly with refeeding
Murray et al[33], 2020	To identify the frequency of FED symptoms and evaluate the relations between FED symptoms, gastrointestinal symptoms, and gastric retention	288 patients (ages 17-78 yr; 77.5% female). Age 42.7 ± 16.3 yr; BMI 26.3 ± 6.5 (kg/m2). AN 5 (2.0%) Other Specified FED 23 (9.4%) Unspecified FED-Restrictive 24 (8.3%)	GES, NIAS, EDDS, PAGI-SYM, GCSI	FED symptoms: Were common (55%), particularly ARFID symptoms (23%-40%); Were associated with greater GI symptom severity, but not gastric retention

GP: Gastroparesis; GI: Gastrointestinal; AN: Anorexia nervosa; BN: Bulimia nervosa; ED: Eating disorders; HC: Healthy controls; HET: Initial gastric half-emptying time; BMI: Body mass index; SCL-90: Symptom Check List-90; EDI: Eating disorders inventory; EDE-Q: Eating disorders examination-questionnaire; VAS: Visual analogue scale; SDS: Self-rating depression scale; CAS: Cattell anxiety scale; OB: Obesity; MRI: Magnetic resonance imaging; DTPA: Diethylenetriaminepentacetic acid; GCSI: Gastroparesis cardinal symptom index; PAGI-SYM: Patient assessment of upper GI symptoms; GCSI: Gastroparesis cardinal symptom inventory; EDDS: Eating disorder diagnostic scale; FED: Feeding or eating disorder; NIAS: Nine item avoidant/restrictive food intake disorder survey; GES: Gastric emptying scintigraphy; ARFID: Avoidant/restrictive food intake disorder.

Table 2 Studies analyzing the association between functional dyspepsia and eating disorders

Ref.	Aims	Study population	Assessment instruments	Results and conclusions
Santonicola et al[37], 2012	Prevalence of FD	20 AN, 6 BN, 10 EDNOS, 9 CT, 32 OB, 22 HC	Rome III criteria (18 questions diagnosis of FD and its subgroups PDS and EPS)	90% AN, 83.3% BN, 90% EDNOS, 55.6% OB and 18.2% CT met PDS criteria. Emesis was present in 100% BN patients, 20% EDNOS, 15% AN, 22% of CT subjects, 5.6% HC. Postprandial fullness intensity-frequency score was significantly higher in AN, BN, EDNOS. Nausea and epigastric pressure were increased in BN and EDNOS
Porcelli et al[38], 1998	Presence of lifetime ED in patients referred for FGID	127 consecutive patients (42 FD, 28 IBS 20 FAP, 37 with FD and IBS; male and 83 females; 163 control subjects gallstone disease	GSRS; HADS (HADS-A and HADS-D)	Past ED were significantly more prevalent in FGID (15.7%) than in gallstone disease patients (3.1%) (chi-square = 14.6, P < 0.001). FGID patients with past ED were significantly younger, more educated, more psychologically distressed, more dyspeptic, and more were women than FGID patients without past ED
Cremonini et al[39], 2009	Severity of BE episodes would be associated with upper and lower GI symptoms	4096 subjects (population-based survey of community residents found through the medical record linkage system) > 18 yr	Questionnaire measuring GI symptoms, frequency of BE episodes and physical activity level	BE disorder: Was present in 6.1% subjects, was independently associated with upper. GI symptoms: Acid regurgitation heartburn, dysphagia, bloating and upper abdominal pain, was associated with lower GI symptoms: diarrhea, urgency, constipation and feeling of anal blockage. The associations independent of the level of obesity
Jáuregui et al[40], 2011	QoL in FD patients psychopathological features that underlie the FD	245 people (mean age 28.36 ± 11.26 yr; 189 female and 56 male) 78 patients with ED (70 female and 8 male, mean age 22.88 ± 8.28 yr), 90 university students with associated FD (76 female and 14 male, mean age 22.49 ± 4.27 yr); 77 psychiatric patients (non-ED) (43 female and 34 male, mean age 40.78 ± 9.40 yr)	NDI-SF, BDI, STAI, TSF-Q, VAS	Satiation and bloating were significantly higher in ED patients. Correlations between dyspepsia and TSF were initially positive and significant in all cases, but significance was only maintained in the group of ED patients. Predictors of quality of life in ED patients: dyspepsia, depressive symptomatology, TSF-conceptual, TSF-interpretative and total TSF
Santonicola et al[41], 2019	Relationship among anhedonia, BED and upper gastrointestinal symptoms in 2 group of morbidly OB with and without SG	81 OB without SG, 45 OB with SG, 55 HC	BDI, STAI, SHAPS, ROME IV criteria for FD and its subtypes	OB without SG showed a higher prevalence of PDS, mood disorders and anxiety when positive for BE behavior compared to those negative for BE behavior, no differences were found in SHAPS score. OB with SG showed a higher prevalence of PDS compared to OB without SG. BED and depression are less frequent in the OB with SG, while state and trait anxiety are significantly higher. The more an OB with SG is anhedonic, less surgical success was achieved

FD: Functional dyspepsia; ED: Eating disorders; HC: Healthy controls; AN: Anorexia nervosa; BN: Bulimia nervosa; EDNOS: Eating disorders not otherwise specified; CT: Constitutional thinners; OB: Obesity; PDS: Postprandial distress syndrome; EPS: Epigastric pain syndrome; FGID: Functional gastrointestinal disorders; IBS: Irritable bowel syndrome; FAP: Functional abdominal pain; GSRS: Gastrointestinal symptoms rating scale; HADS: Hospital Anxiety and Depression Scale; BE: Binge eating; GI: Gastrointestinal; QoL: Quality of life; NDI-SF: Nepean Dyspepsia Index-Short Form; BDI: Beck Depression Inventory; STAI: State-Trait Anxiety Inventory; TSF-Q: Thought Shape Fusion-Questionnaire; VAS: Visual Analogue Scales; SG: Sleeve gastrectomy; SHAPS: Snaith-Hamilton pleasure scale.

Table 3 Studies analyzing the association between functional constipation and eating disorders

Ref.	Aims	Study population	Assessment instruments	Results and conclusions
Chun et al[47], 1997	Colorectal function measuring colonic transit and anorectal function in AN with constipation during treatment with a refeeding program	Prospective study 13 AN females; 20 age-matched, female HC	Radiopaque marker technique; anorectal manometry	Colonic transit is normal/returns to normal in the majority of AN patients once they are consuming a balanced weight gain or weight maintenance diet for at least 3 wk
Sileri et al[48], 2014	Prevalence and type of defecatory disorders in AN patients	85 patients (83 female and 2 male); mean age 28 ± 13 yr; BMI 16 ± 2 kg/m2; 57 HC, BMI 22 ± 3 kg/m2	WCS, OD score, FISI	All results influenced by the severity of the disease (BMI; duration). The percentage of defecatory disorders rises from 75 to 100% when BMI is < 18 kg/m2 and from 60% to 75% when the duration of illness is ≥ 5 yr (P < 0.001 and P = 0.021)
Chiarioni et al[49], 2000	Anorectal and colonic function in AN patients complaining of chronic constipation	12 AN female (age 19-29 yr) chronic constipation. 12 female HC	Anorectal manometry; radiopaque technique; test of rectal sensation	AN patients: anorectal motor abnormalities (slow colonic tranzit time, pelvic floor dysfunction)
Boyd et al[50], 2005	Prevalence and type of FGIDs in AN, BN and EDNOS patients; relationships between psychological features, eating-disordered attitudes and behaviours, demographic characteristics and the type and number of FGIDs	101 consecutive female AN (n = 45, 44%), EDNOS (n = 34, 34%), BN (n = 22, 22%). Mean age 21 yr	Rome II modular questionnaire GI, ENS, BDI, STAI, BSI somatization subscale, EEE-C, version 4, EDI-2, EAT	52% IBS (constipation-predominant 22%, diarrhoea-predominant 6%, alternating 24%), FH (51%), FAB (31%), FC (24%), FDys (23%), FAno (22%). 52% of patients exhibited 3 or more coexistent FGID diagnoses. Psychological variables (somatization, neuroticism, state and trait anxiety), age and binge eating were significant predictors of specific, and > 3 coexistent FGIDs
Murray et al[51], 2020	Frequency of and relation between EDs and constipation in patients with chronic constipation referred for anorectal manometry	279 patients with chronic constipation (79.2% female). Average age (SD) 46.6 ± 17.2 yr	EAT, PAC-SYM, HADS, VSI, ARM, colonic transit testing (24 radiopaque markers)	19% had clinically significant ED pathology. ED pathology might contribute to constipation via gastrointestinal-specific anxiety
Dykes et al[52], 2001	Past and current psychological factors associated with slow and normal transit constipation.	28 consecutive constipated female patients, mean age 38.2 yr (SD 10.8 yr)	SCID, SF-36, EAT	1/5 current affective disorder, 2/3 previous affective disorder, 1/3 distorted attitudes to food
Waldholtz et al[30], 1990	Type and frequency of GI symptoms. To follow symptoms during refeeding prospectively. Guidelines for gastrointestinal testing and intervention in hospitalized AN patients	16 consecutive AN patients chronically ill (4.5 ± 1.2 yr); 71.6% ± 2.9% of matched population weight, 12 HC	AN patients rated on 12 gastrointestinal symptoms before and after nutritional rehabilitation GISS (24 questions); blood tests physical examination	Belching did not improve during treatment; no patients required endoscopy, x-ray evaluation, or antipeptic regimens; although severe gastrointestinal symptoms are common in AN, they improve significantly with refeeding

AN: Anorexia nervosa; BN: Bulimia nervosa; EDNOS: Eating disorders not otherwise specified; HC: Healthy controls; BMI: Body mass index; WCS: Wexner constipation score; OD score: Obstructed defecation score; FIOSI: Fecal incontinence severity index; FGIDs: Functional gastrointestinal disorders; ENS: Eysenck neuroticism scale; BDI: Beck Depression Inventory; STAI: The State-Trait Anxiety Inventory; BSI: Brief Symptom Inventory; EEE-C: Eating and Exercise Examination/computerized; EDI-2: Eating Disorder Inventory-2; EAT: Eating attitudes test; ED: Eating disorders; IBS: Irritable bowel syndrome; FH: Functional heartburn; FAB: Functional abdominal pain disorder; FC: Functional constipation; Fano: Functional anorectal pain disorder; PAC-SYM: Patient Assessment of Constipation Symptom Questionnaire; VSI: Visceral Sensitivity Index; ARM: High-Definition Anorectal Manometry; SCID: Structured Clinical Interview for DSM; SF-36: Short Form (36) Health Survey.