Steroid glycosides extracted from the succulent plant Hoodia gordonii are suggested to have appetite-suppressant effects both in animals and humans. Yet, the mechanisms underlying the putative satiety action of Hoodia steroid glycosides are not fully understood. We found that H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine (EC) cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve which afferents terminate in the gut wall. Recent data show that G protein-coupled receptors signaling bitter taste (T2Rs) are expressed in both rodent and human gastrointestinal tract. It was further demonstrated that bitter sensing is functional in mouse STC-1 EC cells and leads to CCK secretion via increased intracellular Ca²⁺ concentrations. Based on the bitter taste of H. gordonii purified extracts, we assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. Removing an essential structural feature from the steroid glycoside inhibited H.g.-12-induced Ca²⁺ increase in TAS2R14-expressing HEK cells and abolished H.g.-12-induced CCK secretion from human EC cells. Similarly, a nonspecific bitter receptor antagonist abolished H.g.-12-induced CCK secretion in HuTu-80 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control. Our data also provide additional evidence that bitter taste-sensing mechanisms are coupled to hormone release from EC cells in the intestine. Moreover, we identified a natural agonist of TAS2R7 and TAS2R14 for further studies on the role of bitter receptors in satiety control and food intake.

The aim of the present pilot study was to evaluate the usefulness of a test meal containing lactulose in the non-invasive assessment of visceral sensitivity in irritable bowel syndrome (IBS), and to identify subsets of IBS patients based on gastrointestinal (GI) symptom generation. We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served three test meals consisting of a 400-ml liquid breakfast alone or containing lactulose (15 or 25 g) in a double-blind crossover design. Seven GI symptoms, overall digestive comfort, and exhaled H₂/CH₄ were assessed at baseline and every 15 min during 4 h after meal intake. Anxiety and depression were assessed only at baseline. A mapping of the seven GI symptoms was done using a Principal Component Analysis (4 h mean area under the curve, AUC). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters. All three tests were well tolerated. The 25 g lactulose challenge enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on bloating, distension, and discomfort symptoms (2,457 (2,043–2,872), 2,450 (1,910–2,990), 2,602 (2,126–3,079) vs. 537 (383–691), 619 (458–780), 643 (432–854); 4 h mean AUC; P<0.0001), overall digestive comfort (1807 (1318–2295) vs. 3350 (2942–3758); 4 h mean AUC; P<0.0001), and anxiety at baseline (9.2 (7.0–11.5) vs. 5.5 (4.2–6.9); Hospital Anxiety and Depression scale anxiety mean scores; P=0.003). This clustering was independent of the Rome III subtype and the amount of exhaled H₂/CH₄. The lactulose challenge test seems to be a promising tool to assess visceral sensitivity in IBS, and to subgroup IBS patients based on their symptom pattern.

Summary: Background: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet‐surveyed countries met Rome IV criteria for disorders of gut–brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms.Aims: To explore the prevalence and demographic distribution of sub‐diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs.Methods: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions.Results: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub‐diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non‐GI group). Sub‐diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub‐diagnostic group was intermediate between the non‐GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment.Conclusions: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub‐diagnostic group has reduced QoL, greater psychological and non‐GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non‐GI individuals. This suggests that many in this sub‐diagnostic group might benefit from healthcare services or symptom self‐management advice.