Irritable Bowel Research Articles

Harnessing hybrid molecules for drug development

Harnessing hybrid molecules for drug development Stoyanka Nikolova, Professor from Paisii Hilendarski Plovdiv University, discusses the potential of harnessing hybrid molecules for drug development and their possible application in addressing the clinical challenge of irritable bowel syndrome. Irritable bowel syndrome (IBS) remains a clinical challenge. It’s the most common gastrointestinal disorder. IBS has no definitive treatment but could be controlled by non-pharmacologic management, eliminating some exacerbating factors such as certain drugs, stress conditions, and changes in dietary habits. Intestine peristaltic reflexes and sensory relays are significantly regulated by serotonin, predominantly found in intestine enterochromaffin cells.

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

Perceived healthiness of foods, food avoidance and diet-related anxiety in individuals with self-reported irritable bowel syndrome: a cross-sectional study

BackgroundIrritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the intake of food is known to exacerbate symptoms. Experiencing food related symptoms can lead to avoidance of food, and cause anxiety related to food intake. We aimed to explore perceptions of the healthiness of food, food avoidance, and food-related worry and anxiety among individuals with and without IBS.MethodsThis study was based on a survey conducted in January-February 2017. In total, 2000 participants aged 20–65 were invited by postal letter randomly obtained through the Swedish state personal address register. The questionnaire included aspects of socioeconomic position, different disorders including IBS and food intolerances, food avoidance, and food-related worry or anxiety.ResultsIn total, 538 participants were included in this study, of whom 8.4% (n = 45) reported having IBS. There were few differences regarding the perceived healthiness of foods between individuals with and without IBS. Participants with IBS avoided gluten (OR 3.45, p = 0.002), lactose (OR 5.0, p < 0.001) and alcohol (OR 2.0, p = 0.042) more frequently than individuals without IBS, and avoidance was driven by abdominal pain. Participants with IBS also reported feeling more worried and having anxiety about diet than those without IBS (p = 0.032 and p = 0.002, respectively).ConclusionThis study indicates that individuals with IBS perceive most foods as equally healthy as individuals without IBS. Having IBS increases the odds of avoiding gluten, lactose, and alcohol. Worry and anxiety related to diet were more common among individuals with IBS, and these aspects need to be considered both in clinical practice and in future research.

Adapted Low-FODMAP Diet in IBS Patients with and without Fibromyalgia: Long-Term Adherence and Outcomes.

A low-FODMAPs Diet (LFD) is considered a "second line" dietary strategy for irritable bowel syndrome (IBS) but, after a period of strict restriction of all FODMAP foods, it has to be adapted and tailored to each patient (AdLFD). Fibromyalgia often coexists with IBS in up to 65% of cases. Our aims were to evaluate if comorbid fibromyalgia influenced the long-term clinical outcomes and adherence to an AdLFD in IBS patients. IBS patients with or without fibromyalgia who had started an AdLFD were enrolled. Patients had been evaluated before starting the LFD (T0). After a mean follow-up of 62.5 ± 22.7 months (T1), they were re-evaluated using questionnaires on disease severity, bowel habits, psychological status, and adherence to AdLFD. In total, 51 IBS patients entered the study. Nineteen of them had comorbid fibromyalgia. Thirty patients reported a reduction in symptom severity at T1 in comparison with T0. Despite some slight differences in single IBS Symptom Severity Score items, comorbid fibromyalgia did not influence the IBS-SSS total score at T1. Patients with comorbid fibromyalgia showed a higher Hospital Anxiety and Depression Scale (HADS) score at baseline. A total of 44 patients showed good long-term adherence to the AdLFD. All patients improved their HADS score and had long-term adherence to the AdLFD. Comorbid fibromyalgia showed only a slight influence on long-term outcomes of an AdLFD on IBS symptoms, without affecting the relief of global symptoms. No influence on long-term adherence to AdLFD was detected. Hence, this approach can be taken into account in fibromyalgia patients for a nonpharmacological management of IBS symptoms. However, multicentric studies on larger samples would be welcome in the future.

Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options.

Irritable bowel syndrome (IBS) is a condition that significantly impacts the lifestyle, health, and habits of numerous individuals worldwide. Its diagnosis and classification are based on the Rome criteria, updated periodically to reflect new research findings in this field. IBS can be classified into different types based on symptoms, each with distinct treatment approaches and some differences in their pathophysiology. The exact pathological background of IBS remains unclear, with many aspects still unknown. Recent research developments suggest that disorders in the brain-gut-microbiota axis are key contributors to the symptoms and severity of IBS. The central nervous system (CNS) interacts bidirectionally with intestinal processes within the lumen and the intestinal wall, with the autonomic nervous system, particularly the vagus nerve, playing an important role. However, the enteric nervous system (ENS) is also crucial in the pathophysiological pathway of IBS. The apeline-corticotropin-releasing factor (CRF)-toll-like receptor 4 (TLR4) signaling route via enteric glia and serotonin production in enteroendocrine cells at the enteric barrier are among the most well-understood new findings that affect IBS through the ENS. Additionally, the microbiota regulates neuronal signals, modifying enteric function by altering the number of enteric bacteria and other mechanisms. Given the limited therapeutic options currently available, it is essential to identify new treatment targets, with the brain-gut axis, particularly the enteric nervous system, being a promising focus. This study aims to delineate the molecular mechanisms that induce IBS and to suggest potential targets for future research and treatment of this potentially debilitating disease.

New Role of the Serotonin as a Biomarker of Gut-Brain Interaction.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions, especially in the gut and brain. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain, and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

Oxytocin Analogues for the Oral Treatment of Abdominal Pain.

Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon-innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery. However, the low gastrointestinal stability of OTR's endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development. Here, we report the development of potent and fully gut-stable OT analogues, laying the foundation for a new area of oral gut-specific peptide therapeutics. Ligand optimisation guided by structure-gut-stability-activity relationships yielded highly stable analogues (t1/2 >24 h, compared to t1/2 <10 min of OT in intestinal fluid) equipotent to OT (~3nM) and with enhanced OTR selectivity. Intra-colonic administration of the lead ligand significantly reduced colonic mechanical hypersensitivity in a concentration-dependent manner in a mouse model of chronic abdominal pain. Moreover, oral administration of the lead ligand also displayed significant analgesia in this abdominal pain mouse model. The generated ligands and employed strategies could pave the way to a new class of oral gut-specific peptides to study and combat chronic gastrointestinal disorders, an area with substantial unmet medical needs.

Yunpi Rougan Prescription in Treating Constipation-Predominant IBS: Clinical Observation and Gut Microbiota Effects.

Constipation-predominant irritable bowel syndrome (IBS-C) is a chronic functional intestinal disease that can significantly reduce patients' quality of life. This study aims to evaluate the clinical effect and mechanism of YunPi RouGan (YPRG) prescription on IBS-C patients with liver-depression and spleen-deficiency syndrome. 42 IBS-C patients receiving treatment at Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to March 2023 were recruited and randomly assigned to either the treatment or control group, with 21 patients in each group. The patients received either a YPRG prescription or a linalotide capsule for 4 weeks. A series of scales were utilized to evaluate the clinical symptoms, psychological aspects, and quality of life in IBS patients. Meanwhile, fresh fecal samples were collected to analyze the changes in gut microbiota by 16SrDNA sequencing. In terms of clinical treatment, both YPRG prescription and the first-line drug linaclotide have similar effects for IBS-C. However, YPRG prescription has demonstrated significant improvements in several symptoms, such as abdominal distension and belching. Furthermore, it has been shown to upregulate the diversity of gut microbiota and induce changes in the types of dominant microbiota in IBS-C patients. At the phylum level, Firmicutes and Bacteroides increased, while Proteobacteria, actinobacteria, and desulphurobacteria decreased. At the genus level, Bacteroides, Spirillum, Clostridium praxis, Roxella, Para-salmonella, Haemophilus, koala bacillus, Micrococcus rare, Spirillum, and Streptococcus increased significantly. The effect of YPRG prescription on improving the clinical symptoms of IBS-C may be attributed to its potential to regulate gut microbiota.

Prospective Analysis of Dietary Risk Factors Involved in the Occurrence of Irritable Bowel Sydrome among Students in Ivory Coast

This is a prospective cross-sectional study, with a descriptive and analytical aim, with the main objective of analyzing the dietary risk factors involved in the occurrence of irritable bowel syndrome among students in Côte d'Ivoire. This investigation follows the work of Amoikon et al., (2016) who revealed among students an unbalanced, unstructured and poorly hydrated diet with a high prevalence of abdominal irritation syndrome. Thus, a new food and health consumption survey was carried out from October 15, 2016 to February 17, 2017, in a population of 1,228 student volunteers, with an average age of 22.5 years, dominated by males. It revealed a high prevalence of intestinal irritation syndrome (47.7%) and dietary imbalance. After analyzing the relationship between eating habits and pathology, it turned out that high consumption of red meat, soft drinks, non-alcoholic exciting products, spicy products and low water consumption were the factors risk of the occurrence of the pathology among the respondents. To this end, it would be important to carry out nutritional education sessions on university campuses across the country, with a view to improving their eating habits, their food security and their health conditions.

Relationship Between High Frequency Component of Heart Rate Variability and Delta EEG Power During Sleep in Women With Irritable Bowel Syndrome Compared to Healthy Women.

To explore the relationship between the high frequency (HF) heart rate variability (HRV) and electroencephalogram (EEG) delta band power in women with irritable bowel syndrome (IBS) versus healthy control women. Twenty women with IBS and twenty healthy controls were studied over three consecutive nights using polysomnography in a sleep laboratory. To avoid the first night effect, only second-night data were analyzed. Power spectral analysis was applied to HRV and EEG recordings. The linear system coherence/phase analysis assessed the relationship between normalized HF power of HRV and normalized delta band power of EEG during the first four NREM-REM sleep cycles. Women with IBS exhibited a significantly higher percentage of NREM sleep, higher normalized HF, lower normalized low frequency (LF) and decreased LF/HF ratio of HRV in the first four NREM-REM sleep cycles compared to controls. Additionally, their normalized delta band power was significantly lower in these sleep cycles and over the whole night. The phase shift between HF and delta band power was significantly longer in the IBS group. While the coherence between normalized HF and normalized delta band power was lower in the IBS group, the difference was not statistically significant. The coherence/phase analysis showed a dysregulated interaction between autonomic and central nervous systems in women with IBS, manifested by increased lag time between cardiac and EEG delta band power compared to healthy controls. Whether this dysregulation contributes to the pathophysiology of IBS remains to be determined.

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome Irritable bowel syndrome (IBS) is a common, chronic gastrointestinal disorder characterised by recurring abdominal pain and discomfort. This project will work under the hypothesis that IBS is linked to a malfunctioning of the brain-gut communication axis and proposes to address this dysfunction through transcutaneous electrical vagus nerve stimulation. To assist in identifying IBS patients suitable for this treatment, the study team aims to develop a neural signature using biometrics and neuroimaging. The study has the potential to revolutionise the treatment of IBS and other pain disorders, providing personalised and effective therapies.

Compendium of Bifidobacterium-based probiotics: characteristics and therapeutic impact on human diseases

The human microbiota, a complex community of microorganisms residing in and on the human body, plays a crucial role in maintaining health and preventing disease. Bifidobacterium species have shown remarkable therapeutic potential across a range of health conditions, thus being considered optimal probiotic bacteria. This review provides insights into the concept of probiotics and explores the impact of bifidobacteria on human health, focusing on the gastrointestinal, respiratory, skeletal, muscular, and nervous systems. It also integrates information on the available genetic bases underlying the beneficial effects of each bifidobacterial probiotic species on different aspects of human physiology. Notably, Bifidobacterium -based probiotics have proven effective in managing gastrointestinal conditions such as constipation, antibiotic-associated diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Helicobacter pylori infections. These benefits are achieved by modulating the intestinal microbiota, boosting immune responses, and strengthening the gut barrier. Moreover, Bifidobacterium species have been reported to reduce respiratory infections and asthma severity. Additionally, these probiotic bacteria offer benefits for skeletal and muscular health, as evidenced by Bifidobacterium adolescentis and Bifidobacterium breve , which have shown anti-inflammatory effects and symptom relief in arthritis models, suggesting potential in treating conditions like rheumatoid arthritis. Furthermore, probiotic therapies based on bifidobacterial species have shown promising effects in alleviating anxiety and depression, reducing stress, and enhancing cognitive function. Overall, this review integrates the extensive scientific literature now available that supports the health-promoting applications of probiotic Bifidobacterium species and underscores the need for further research to confirm their clinical efficacy across different body systems.

Comparison of 4-week versus 8-week dietitian-led FODMAP diet group education sessions in tertiary care clinical practice for irritable bowel syndrome: A service evaluation.

The implementation of the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet for irritable bowel syndrome (IBS) can be effectively delivered by dietitians in group settings. The initial FODMAP restriction phase is recommended to be followed for 4 weeks; however, limited efficacy data exist for 4-week FODMAP restriction in group education clinical practice. We aimed to compare 4-week versus 8-week FODMAP group treatment pathways on clinical outcomes using a prospective service evaluation design of IBS patients attending FODMAP restriction (baseline) and reintroduction (follow-up) group sessions (between 2015 and 2019). Clinical outcomes included global symptom question (GSQ) measuring satisfactory relief, gastrointestinal symptom rating scale (GSRS), stool frequency (SF), stool consistency using Bristol stool form scale (BSFS), diet acceptability, patient satisfaction with group sessions and dietary adherence. Logistic regression was used to test for differences in treatment effects when clinical outcomes were compared between groups. Patients (n = 284) included were aged 18 to 86 years (mean ± SD [standard deviation], 44.6 ± 15.5), 80% female, and were split into 4-week (41%, 117/284) versus 8-week (59%, 167/284) pathways with no differences in baseline characteristics. Mean ± SD time gap between baseline and follow-up was 4.6 ± 0.9 weeks in the 4-week pathway and 9.6 ± 3.3 weeks in the 8-week pathway. When groups were compared at follow-up, no statistical differences were observed in any measures (GSQ, GSRS, SF, BSFS, dietary adherence, diet acceptability and patient satisfaction). A 4-week dietitian-led group FODMAP treatment pathway is as clinically effective and maintains patient acceptability when compared to 8-weeks and should be considered as part of routine clinical practice.

Impact of Irritable Bowel Syndrome upon Female s' Health Related Quality of Life

متلازمة القولون التهيجي هو من الحالات الشائعة الحدوث والمتصفه بالم في البطن مع الاسهال او الامساك. وتشير الاحصائيات ان نسبة حدوث المرض هي 1 من بين 1000 فرد مريض سنويا" ونسبة الاصابة تختلف مابين 4-13% ونسبة انتشار المرض من 6-20% وهذه الحالة المرضية كثيرة الانتشار بين النساء عنه عند الرجال ، وتحدث مابين الاعمار 15 و 65 مسببة" مضاعفات طويلة الامد. ان نسبة 15-20% من الاصابات عند النساء تكون مجهولة السبب ويعتقد البعض ان الاضطرابات الجسمية –النفسية قد تكون سبب في ظهور الحالة المرضية واشارت بعض الدراسات ان النشاطات المناعية في الجسم قد يكون عامل اخر في ظهور الحالة . لتهيج القولون العصبي تأثير كبير على الانسان من خلال استمرارية ظهور الاعراض وبشكل مزمن مما يؤثر ويعيق النشاطات والمهارات اليومية بالاضافة لتاثيرة على الوضع النفسي والعاطفي للفرد، لذا لابد من ايجاد وسائل مساعدة لمعالجة وايقاف هذه العلامات المستمرة ولكي يتكيف المريض مع حالته الصحية دون التاثير على حياته العامة. دراسة وصفية تحليلية بدأ العمل بها مابين 8تموز 2008 ولغاية 29 من تشرين الاول 2009 للتعرف على تاثير تهيج القولون العصبي على نوعية حياة النساء. اجريت الدراسة الحالية في مستشفى امراض الجهاز الهضمي والكبد في بغداد.عينة غرضية اجريت على 100 مريضة مصابة بتهيج القولون العصبي. تكونت أداة الدراسة من جزئين مع صفحة الترحيب بالمشاركين في الدراسة الجزء الاول: المعلومات اليموغرافية للمريض. الجزء الثاني:تم استعمال المقياس العالمي المتضمن 36فقرة الذي يتعلق بقياس نوعية الحياة الصادر من منظمة الصحة العالمية والمتضمن المحاور التالية ( الوضع الصحي، الوظائف الجسمية، الدور الوظيفي، الدور العاطفي، الوظيفة الاجتماعية، الالم الجسمي، الفعاليات، الصحة العقلية، الصحة العامـة). اظهرت نتائج الدراسة ل(100) امراة مصابة بتهيج القولون العصبي ان 30%من النساء هن من الفئات العمرية (28-37) سنة و 54% منهن متزوجات ومستمرة حياتهم الزوجية ومعظم المصابات هن موظفات (61%) وغالبية المصابات هن خريجات جامعيات (42%) واظهرت الدراسة ان نصف العينة من ذوات الدخل العالي ونسبة 47% من المصابات هن من النوع المتناوب بين الامساك والاسهال لتهيج القولون وكان الدور الجسمي والدور العاطفي قد حصل على اقل متوسط حسابي عن المحاور الاخرى لمقياس نوعية الحياة. توصلت الدراسة ان لتهيج القولون العصبي تاثير سلبي على نوعية حياة النساء اللواتي ضمن الفئات العمرية( 28-37) وعلى النساء المطلقات والنساء الموظفات في المؤسسات الحكومية.

Symptom bothersomeness and life interference support Rome clinical criteria as clinically relevant indicators of DGBI.

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI). The Rome IV criteria are the gold standard for research when diagnosing DGBI. However, bothersomeness, or the degree to which symptoms are distressing or disruptive to a person's daily life, is a potential treatment-seeking motivator that is not assessed by the Rome criteria. The Rome Foundation developed and published diagnostic criteria for clinical practice that include bothersomeness. We aimed to evaluate these constructs via patient focus groups to determine what prompts healthcare-seeking as a means to assess its value in the Rome clinical criteria. Adults meeting Rome IV criteria for IBS, FD, or both participated in focus groups in Australia and the United States. Semi-structured interview transcripts were analyzed using Template Thematic Analysis, with three a priori and other a posteriori themes refined iteratively through team discussion and consensus. Participants confirmed the frequency and duration of symptoms was not sufficient to reflect illness experience. Four major themes emerged: (1) Bothersomeness should be included in assessments of IBS and FD; (2) Patients find many DGBI symptoms bothersome; (3) Bothersomeness traverses multiple domains of quality of life; (4) Patients may hesitate to seek medical advice due to past negative experiences. These findings support the value of the Rome Clinical Criteria. They emphasize the importance of expanding assessments of patients with DGBI to include how bothersome they perceive symptoms to be, how much symptoms interfere with their daily life, and what may moderate their decisions to seek treatment.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 μg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

7654 Unusual Case of Lipodystrophy: A Novel Disease Phenotype?

Abstract Disclosure: M. Celik Guler: None. E.D. Frontera: None. K. Hoose: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. L. Douyon: None. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Ionis Pharmaceuticals Inc., Fractyl, GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Background: Lipodystrophy syndromes (LD) are rare disorders characterized by varying degrees of adipose tissue deficiency that can predispose individuals to severe metabolic complications. Although these syndromes are traditionally subclassified based on inheritance patterns and the degree of adipose tissue loss, patients may exhibit highly heterogeneous clinical presentations. In this context, we report a unique case of partial lipodystrophy with an unusual distribution of adipose tissue that likely represents a novel syndrome and challenges conventional phenotypes. Clinical Case: A 60-year-old Puerto Rican female patient with medical history of type 1 diabetes mellitus (DM), obesity, hyperlipidemia, irritable bowel syndrome, asthma, and coronary artery disease was referred to us for unexplained asymmetric distribution of adipose tissue. She had chronic left posterolateral hip pain and lipoatrophy in her left lower extremity. Her medical history showed that she was born approximately 7 lbs., with no evidence of trauma during delivery. Her mother was given an unknown medication for improving circulation to the placenta. She had a morphea like rash on the arms and chest wall more prominent on the left upper body at birth. In addition, a dimple on her hip was noticed by her mother during the early stages of infancy. Despite the normal progression of neurological development (walking/climbing stairs), she always had a very mild limp. Also, her right arm was always 2 inches larger than her left arm. When she gained weight, she also put on more asymmetric weight on the left side of the abdomen and left lower torso. She had been treated with insulin injections since she was diagnosed with diabetes at the age of 11. She never demonstrated any islet cell specific antibodies. She had a normal weight until pregnancy at the age of 27, during which she gained 20 lbs. Her weight continued to increase over time, and the maximum was 212 lbs. Her examination reveals a BMI of 41.46 kg/m² with excess fat in the right arm, mid-section, left thigh, and left mons pubis. Conversely, only the left leg appears to demonstrate specific fat atrophy, with a near-total loss of adipose tissue starting from the mid-gluteal region. The hip MRI result reported moderate osteoarthritis of the left hip. EMG revealed signs of length-dependent sensorimotor axonal polyneuropathy and long duration/large amplitude motor unit potentials isolated only in the left medial gastrocnemius muscle. Triglyceride level was 73 mg/dL, HbA1c level was 6.8%, with an average total insulin dosage of around 43 IU/day. There was no history of pancreatitis due to hypertriglyceridemia. Conclusion: Our case highlights the heterogeneity of the lipodystrophy spectrum with a novel presentation of lipodystrophy. In addition, there may be homeostatic control of deposition of fat to seek symmetry between upper versus lower and right versus left sided depots. Presentation: 6/1/2024

Review article: The role of the gut-brain axis in inflammatory bowel disease and its therapeutic implications.

Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting. We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024. The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients. Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

9334 Pancreatic Adenocarcinoma Presenting As Diabetic Ketoacidosis

Abstract Disclosure: J. Alvarez: None. M.H. Horani: None. Background: Pancreatic adenocarcinoma is often diagnosed at an advanced stage due to late onset of clinical features including poor appetite, weight loss, weakness, epigastric pain, and rarely impaired glucose tolerance. In patients who present with impaired glucose tolerance or diabetic ketoacidosis without prior history of diabetes, pancreatic adenocarcinoma should be considered. Clinical Case: Patient is a 45-year woman with depression, HTN, irritable bowel syndrome who was found unresponsive by family and presented to the ED for acute encephalopathy. On exam, she was obtunded, tachypneic, with fruity-smelling breath and dry mucous membranes. Initial labs showed glucose of 950 mg/dL (70-99 mg/dL), lipase 539 U/L (8-78 U/L), lactic acid 4 mmol/L 0.5-2 mmol/L), ketone-BHB 170.75 mg/dL (0-2.81 mg/dL), A1c 16.5%. She had no prior history or family history of diabetes. She was admitted to hospital for DKA management.CXR to evaluate dyspnea showed bilateral opacities so CT chest/abdomen/pelvis without contrast was ordered. This showed bilateral multilobar pneumonia, trace pleural effusions, 6.7 x 3.8 cm lobulated fluid collection along pancreatic tail, 12.1 x 6.6 x 4.4 cm RLQ cystic lesion and 4.4 cm lesion vs loculation along the right pelvic sidewall.Initially, GI recommended repeat imaging of the pancreas in 4-6 weeks. OBGYN was consulted for pelvic masses and recommended IR-guided biopsy of right pelvic mass which showed rare mildly atypical mucinous epithelium present, cystic mucinous neoplasm cannot be excluded.CEA and CA125 tumor markers returned elevated. These biopsies showed adenocarcinoma (solid component) and rare atypical mucinous epithelium consistent with cystic mucinous neoplasm (cystic fluid). Patient was deemed medically stable for discharge with recommended follow-up to appropriate specialists. Following discharge, she was officially diagnosed with Stage III (cT4, cN0, cM0) pancreatic adenocarcinoma and started on appropriate chemotherapeutic regimen. Discussion: The current understanding is long-standing type 2 diabetes mellitus as a risk factor for pancreatic cancer based on previous studies.The inverse relationship of pancreatic cancer causing new onset diabetes is more rare, but if cancer is suspected in these patients it could potentially help in the diagnosis of early stage adenocarcinoma. Other case reports have suggested implementation of the enriching new-onset diabetes for pancreatic cancer (ENDPAC) score in addition to CT and EUS as screening for pancreatic cancer may help with earlier diagnosis.

Proinflammatory Diet Increases the Risk of Irritable Bowel Syndrome: A Prospective Study of 129,408 UK Biobank Participants and Mendelian Randomization Analysis.

Patients with irritable bowel syndrome (IBS) often have chronic low-grade inflammation in the intestinal mucosa. Some dietary components are known to be associated with inflammation. However, there is currently limited research on the relationship between dietary inflammatory potential and the risk of IBS. A total of 129,408 participants in the UK Biobank were included in this study. Energy-Adjusted Dietary Inflammatory Index (E-DII) based on 26 nutrients and the Empirical Dietary Inflammatory Pattern (EDIP) based on 17 food groups were constructed, and on the basis of the tertiles, the continuous score was categorized into proinflammatory, neutral, and antiinflammatory categories. Associations between IBS and E-DII and EDIP were investigated by multivariable Cox proportional hazard models. Potential confounders including sociodemographic, lifestyle, body mass index (BMI), psychological state, type 2 diabetes, and thyroiditis were adjusted. In addition, subgroup analysis and sensitivity analysis were also performed. Finally, a two-sample Mendelian randomization (MR) analysis was employed to explore the independent causality of nutrients and dietary-derived serum antioxidants with IBS. In the cohort study, over a median follow-up period of 13.26years, 2421(1.87%) participants developed IBS. In the E-DII categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with the antiinflammatory category (HR 1.15, 95% CI 1.03-1.28, p = 0.015, p trend = 0.017) and neutral category (HR 1.13, 95% CI 1.01-1.26, p = 0.030, p trend = 0.017). In the EDIP categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with antiinflammatory category (HR 1.19, 95% CI 1.06-1.33, p = 0.002, p trend = 0.002) but no significant association compared with neutral category (HR 1.10, 95% CI 0.99-1.23, p = 0.067, p trend = 0.002). In the MR analysis, genetically determined intake levels of 16 nutrients and 6 dietary sources of circulating antioxidants did not have a causal effect on IBS. Our findings indicate that proinflammatory dietary components are independent risk factors for IBS. However, there is no causal relationship between individual nutrient intake or serum antioxidants from dietary sources and IBS.