Introduction

Diet plays a pivotal role in inflammatory bowel disease (IBD) as it is postulated to mediate inflammation in the gut. Certain foods dysregulate the immune system by altering the intestinal mucosal layer, contributing to microbial dysbiosis¹. There is emerging evidence that specific dietary interventions may promote remission in mild to moderate IBD. However, few studies investigate the role of specific diet patterns in the development of IBD.

Aims & Methods

We aim to describe the nutritional profile in multi-ethnic Asian patients with IBD and compare them to healthy controls. We also aim to demonstrate association of certain diet patterns with increased risk of IBD, by analysis of inflammatory proteins.
The study cohort was sequentially recruited from a single tertiary centre comprising 145 patients with IBD (58.6% Ulcerative colitis (UC) and 41.4% Crohn's disease (CD)), and 112 healthy control, who are individuals undergoing screening colonoscopy with no colonic pathology. A semi-quantitative validated food frequency questionnaire² was administered and nutrients and food group intakes were calculated for patients in g/day. Unsupervised analysis of the nutrient and food group data was done through principal component analysis (PCA). Multivariate linear regression was used to identify nutrients and food groups associated with IBD subtypes while adjusting for age, gender, BMI. and race. Serum protein profiling was performed using the Olink Target 96 Inflammation assay, and spearman correlation was used to associate serum cytokines with nutrient and food groups.

Results

Dietary composition of IBD patients differ significantly from the control as demonstrated by PCA, with discrepancy between PC1 (p<0.0001) and PC2 (p=0.0063) axes which account for 17.9% and 13.0% of the total dietary composition variance. There is no significant difference between UC and CD subgroups.
Participants with IBD were younger (46.9(±14.2) in UC, 44.7(±15.9) in CD, p<0.01), with greater representation of males (72.6% amongst UC, 66.7% amongst CD, p=0.03), and lower proportion of Chinese (50.6% amongst UC, 56.7% amongst CD, p<0.01) as compared to controls. Adjusting for differences in age, gender and ethnicity, sweetened beverages and white bread were dietary elements significantly associated with UC and CD respectively, whereby both groups had increased intake of sweetened beverages and savory bread.(Table 1)
Using paired serum samples and dietary outputs, 39 significant cytokine-dietary elements were identified. Of note, increased consumption of sweetened beverages and fruit juice was associated with increased expression of matrix metalloproteinase-1 (MMP-10) (p<0.01) and reduced expression of interleukin-22 (IL-22) (p=0.03). MMP-10³ regulates the pro-inflammatory cytokines in IBD patients. Conversely, IL-22⁴ promotes mucosal healing, and hence reduced expression may worsen IBD. White bread intake has also been associated with multiple inflammatory proteins including OSM⁵ (p=0.03), EN-RAGE⁶(p=0.03), FGF-23 (p<0.01) and IL-17A (p=0.04), shown from previous studies to be proinflammatory in IBD.

Conclusion

Our study shows a unique dietary profile for patients with and without IBD. There is a direct correlation of certain foods with increased expression of inflammatory proteins in patients with IBD. This suggests dietary profile in patients may affect IBD activity. Further studies may elucidate new nutritional therapy for IBD patients.

References

1. Scott Manski, Nicholas Noverati, Tatiana Policarpo, Emily Rubin, Raina Shivashankar, Diet and Nutrition in Inflammatory Bowel Disease: A Review of the Literature, Crohn's & Colitis 360, Volume 6, Issue 1, January 2024, otad077, https://doi.org/10.1093/crocol/otad077
2. Whitton C, Ho JCY, Tay Z, Rebello SA, Lu Y, Ong CN, van Dam RM. Relative Validity and Reproducibility of a Food Frequency Questionnaire for Assessing Dietary Intakes in a Multi-Ethnic Asian Population Using 24-h Dietary Recalls and Biomarkers. Nutrients. 2017 Sep 25;9(10):1059. doi: 10.3390/nu9101059. PMID: 28946670; PMCID: PMC5691676.
3. Fonseca-Camarillo G, Furuzawa-Carballeda J, Martínez-Benitez B, et al. Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study. Scand J Immunol. 2021 Jan;93(1):e12962.
4. Li LJ, Gong C, Zhao MH, Feng BS. Role of interleukin-22 in inflammatory bowel disease. World J Gastroenterol. 2014 Dec 28;20(48):18177-88. doi: 10.3748/wjg.v20.i48.18177. PMID: 25561785; PMCID: PMC4277955.
5. Sare Verstockt, Bram Verstockt, Kathleen Machiels, et al. Oncostatin M Is a Biomarker of Diagnosis, Worse Disease Prognosis, and Therapeutic Nonresponse in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2021 Oct 18;27(10):1564-1575.
6. Foell D, Kucharzik T, Kraft M, et al. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut 2003;52:847-853

Clinical Case Summary

Clinical case: We present the case of a 67-year-old woman who underwent radical cystectomy with Orthotopic Neobladder (ONB) reconstruction for bladder invasive-neoplasia in August 2023.
In November 2023, the patient was admitted to the Emergency Department for hematuria and de novo anemia (Hgb 7.1g/dL). A pelvic CT scan revealed the neobladder filled with clots and a focus of active bleeding in its antero-inferior wall. Cystoscopy showed two vessels with active bleeding in the intestinal aspect of the mucosa of the urethro-neovesical anastomosis - despite attempts at hemostasis during cystoscopy, bleeding persisted.
Due to worsening anemia and ongoing hematuria after 13 days, Urology consulted Gastroenterology for endoscopic intervention. Endoscopy was performed through the urethra using a high standard endoscope and CO2 – it revealed diffuse bleeding at the urethro-neovesical anastomosis, which was managed with argon-plasma coagulation and purastat application. Octreotide and tranexamic acid therapy were also started. The patient's condition improved post-these measures, and she was discharged home with stable hemoglobin levels (Hgb 8.4g/dL).
However, the patient presented with hematuria again a month and a half later, prompting surgical reintervention with ileal conduit reconstruction.
Discussion: ONB reconstructions involve the creation of a continent neobladder using a segment of the terminal ileum. The overall long-term complication rate of this procedure has been reported to be 40.8%, although hematuria originating in the ileal mucosa is relatively rare. With the gradual increase in cases of neobladder construction, this reality should be taken into consideration. This case underscores the potential for bleeding from the ileal mucosa of the neobladder, necessitating endoscopic intervention. While literature on endoscopy in these cases is scarce, our hemostatic measures temporarily reduced bleeding despite incomplete effectiveness of endoscopic therapy.

References

Qu LG, Lawrentschuk N. Orthotopic Neobladder Reconstruction: Patient Selection And Perspectives. Res Rep Urol. 2019 Dec 11;11:333-341. doi: 10.2147/RRU.S181473. PMID: 31850284; PMCID: PMC6912000.

Introduction

The proportion of patients who take opioid based analgesics and cannabis has not been studied in a large cohort of patients with cyclical vomiting syndrome (CVS) in the UK. It is also unclear whether the efficacy of prophylactic tricyclic antidepressants (TCAs) is impacted by ongoing opioid or cannabis use.

Aims & Methods

(A) To study the burden of opioid and cannabis use in patients with CVS.
(B) To study the clinical response to prophylactic TCA and whether this was augmented by opioid/cannabis intake.
Clinical characteristics and healthcare outcomes of patients diagnosed with ROME IV CVS in a single neurogastroenterology clinic between January 2016 to December 2023 were retrospectively collected. A standardised clinic template was used to collect data relating to age, sex, gastrointestinal symptoms, medication usage, and patient-reported response to TCA. Patients commenced 10mg TCA for 60 days which was up titrated by 10 mg at each routine outpatient consultation (unless poorly tolerated) until clinical remission was achieved or the maxmum dose (50 mg daily) was prescribed. Clinical remission was defined as the absence of stereotypical episodes of vomiting for at least 6 months prior to the last clinic consultation.

Results

95 patients (male 21%, mean age 30.8±11.8 years) were identified and 84 (88%) were seen on at least two or more occasions with a median duration of follow-up of 22 (IQR: 5, 39) months. The treatment outcomes for all patients treated with TCA are outlined in table 1. At the initial consultation, 35 (37%) and 16 (17%) patients took prescribed opioid analgesics and cannabis, respectively. All were provided with drug cessation advice and were prescribed a TCA: only 12/35 (34%) and 11/16 (69%) of patients adhered to drug cessation advice. On follow-up, 100% of patients who adhered to recommendations to stop opioids and cannabis responded to TCA whilst 0% of patients who continued to take opioids/cannabis responded to TCA. Illicit drugs were found at urine drug screening in 5 patients who failed to respond to TCA (cocaine n=2 and heroin n=3).

Conclusion

This is the first UK study reporting the impact of opioid usage and illicit drugs in patients with CVS. TCAs are useful in treating CVS patients providing they do not consume prescribed opioids or illicit drugs.

Introduction

Autoimmune Atrophic Gastritis (AAG) is a chronic immune-mediated condition that mainly affects the body and fundus of the stomach. AAG is often under-diagnosed due to the slow progression of the disease and a variable spectrum of symptoms. Recent data suggests a potential role of altered gastric microbiota in the natural history of AAG, due to the potential overgrowth of bacteria linked to the development of neoplastic complications (neuroendocrine tumors- NETs and gastric cancer) (1,2). Moreover, the same data hypothesizes the use of fecal microbiota as a possible non-invasive marker to diagnose and monitor AAG. Thus, we aimed to prospectively characterize the salivary and fecal microbiota of patients with AAG to provide further insights in this field.

Aims & Methods

We collected salivary and fecal samples from consecutive patients with an established diagnosis of AAG, enrolled at the Gastroenterology Unit of Azienda Ospedale Università Padova from March to June 2023 at the time of endoscopic follow-up examination. All patients needed to be off Proton-Pump Inhibitors, antibiotics, and probiotics for at least one month before enrolment. Stool samples were collected by the patients on the day of the endoscopy, transferred in a buffer solution, and stored at -20°C. Oral samples were collected through salivary commercial kits and freezed at -20°C. Both salivary and faecal samples were analyzed by BMR Genomic (Padua, Italy) that amplified the V3-V4 hypervariable ribosomal RNA region. Sequencing of the 16S rRNA gene V3- V4 region was performed using the Illumina MiSeq. Preliminary analyses were conducted on individual fecal samples compared to an internal population of healthy subjects (provided by BMR genomics) using Qiime2 tools. Shannon–Wiener index was used to calculate α-diversity and then the microbial biodiversity index (MBI) and Dysbiosis Index (DI). Mann–Whitney tests were performed to verify statistical differences in the α-diversity across AAG patients and healthy subjects.

Results

We enrolled 15 AAG patients with a mean age of ± 63 ± 11 years (9/15 females). OLGA 2 stage was reported in 10/15 patients. Sixty percent of the patients showed a MBI between 7.11 and 12.45, indicating that each sample contained phylogenetically similar species. The remaining patients have an index greater than 12.45 compared to the healthy population. More than half of the patients had dysbiosis (>0.082). The highest indices of dysbiosis were found in patients with a history of NET (n=3), gastric cancer (n=1), and previous HP- infection and OLGA 3 stage (n=1). Firmicutes, Bacteroidetes, and Proteobacteria were more frequent phyla found in the fecal samples, whereas Enterobacteriaceae and Streptococcaceae were the most common bacterial families (13/15, 87%). In particular, Klebsiella and Campylobacter pathogens genera were found in some samples. Streptococcus and Prevotella were the most abundant genera found in the salivary samples.

Conclusion

Patients with AAG were found to have a great proportion of Firmicutes and Bacteroidetes, which aligns with the literature (3,4). Moreover, a dominant of Proteobacteria, especially Enterobacteriaceae commonly associated with proinflammatory states, was found. (5) Our preliminary data showed a possible positive association between higher degrees of dysbiosis and a previous history of NET or gastric cancer.

References

1. Parsons BN, Ijaz UZ, D'Amore R, Burkitt MD, Eccles R, Lenzi L, Duckworth CA, Moore AR, Tiszlavicz L, Varro A, Hall N, Pritchard DM. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. PLoS Pathog. 2017 Nov 2;13(11):e1006653.

2. Conti L, Annibale B, Lahner E. Autoimmune Gastritis and Gastric Microbiota. Microorganisms. 2020 Nov 19;8(11):1827.

3. Castaño-Rodríguez N, Goh KL, Fock KM, et al. Dysbiosis of the microbiome in gastric carcinogenesis. Sci Rep. 2017;7(1):15957.

4. Conti L, Borro M, Milani C, Simmaco M, Esposito G, Canali G, Pilozzi E, Ventura M, Annibale B, Lahner E. Gastric microbiota composition in patients with corpus atrophic gastritis. Dig Liver Dis. 2021 Dec;53(12):1580-1587.

5. Rizzatti G, Lopetuso LR, Gibiino G, Binda C, Gasbarrini A. Proteobacteria: A Common Factor in Human Diseases. Biomed Res Int. 2017;2017:9351507.

Disclosure

Nothing to disclose

Introduction

Data on Intestinal Ultrasonography (IUS) in ulcerative colitis (UC) are growing especially in monitoring colonic lesions after therapies. Ultrasonographic parameters derived from studies in Crohn’s disease populations.

Aims & Methods

Aim of our multicenter study was to define IUS parameters of normality and activity in UC patients compared to a healthy control group (HC). Secondary aim was to evaluate severity of colonic lesions using endoscopy as reference standard.
From July 2022 to Oct. 2023, we conducted a multicenter study at 6 IBD centers. Patients (pts) with UC and indication to perform colonoscopy were longitudinally enrolled. HC [no gastrointestinal symptoms, no anemia and normal fecal calprotectin (FC)] were enrolled to establish normal values. The analysis was performed per patient and per segment evaluating colonic wall thickening (CWT), colonic wall flow, Milan Ultrasound Criteria (MUC), Mayo endoscopic score (MES) and partial/full Mayo score. The sample size for UC cohort and HC, the area under (a ROC) curve, Spearman’s correlation among clinical data, FC, IUS and endoscopy were calculated.

Results

180 UC patients and 80 HC were enrolled. In the UC cohort, 53% were male with a median age of 40 years (range 18-78), 64% had extensive colitis and 36% had left colitis. In the HC, 44% were male with a median age of 29 years (range 19-70). Median CWT in comparison to MES in UC patients and median CWT in HC were shown in Table 1. Rectum wall thickening showed higher values than other colonic segments. A CWT> 2.75 mm showed a sensitivity, specificity, NPV and PPV of 54%, 96%, 48% and 97%, respectively, in differentiating UC patients from HC [AUC=0.72]. A rectum wall thickening >4.55 mm showed a sensitivity, specificity, NPV and PPV of 67%, 84%, 56% and 89%, respectively, in differentiating UC patients from HC [AUC=0.82]. A CWT> 3.5 mm showed a sensitivity, specificity, NPV and PPV of 57.4%, 94.3%, 86% and 78%, respectively, in differentiating activity from remission in UC patients [AUC=0.84]. A rectum wall thickening >5 mm showed a sensitivity, specificity, NPV and PPV of 57.5%, 85.7%, 41% and 92%, respectively, in differentiating UC rectal activity from remission [AUC=0.81]. The correlation of the CWT or MUC vs MES was better than clinical data and FC.

Conclusion

Introduction

Crohn’s disease (CD) may manifest as perianal disease (PD) in up to 36% of cases. In the majority, PD occurs simultaneously or after the diagnosis of small bowel CD. Diagnosing CD in patients with isolated PD can be challenging. Small bowel capsule endoscopy (SBCE) has been shown to have a higher diagnostic yield for small bowel findings compatible with CD than other modalities.

Aims & Methods

This study aimed to assess the impact of SBCE as a diagnostic tool for CD in patients with isolated PD.
Retrospective cohort study spanning 2008 to 2023. Adult patients with isolated PD (recurrent fissures, trans-/supra-/extra-sphincteric fistula or abscess) and negative conventional workup for CD (ileocolonoscopy and cross-sectional imaging) who underwent SBCE (Pillcam, Given®) were included. Patients using nonsteroidal anti-inflammatory drugs or with a CD history were excluded. Demographics, biomarkers, SBCE findings and subsequent management were recorded and analyzed.

Results

Forty patients (mean age 40.2 years, 67.5% females) were included. SBCE identified findings compatible with small bowel CD (aphthous ulcerations, linear/circumferential ulcers and stenosis) in 32.5% (13 patients), enabling diagnosis and subsequent treatment in all of them, based on disease severity. In this group, mean previous fecal calprotectin (FC) was 722.2µg/g, but FC was inferior to 200µg/g in 46.2% (6 patients). In 4 patients (10%) with negative SBCE, isolated perianal CD was assumed and immunosuppressors were started. There was no statistically difference in FC of the patients with positive and negative SBCE. Laboratory findings (C-reactive protein, albumin), tobacco use and family history of CD/ulcerative colitis did not show significant associations with SBCE findings.

Conclusion

For patients with PD and a negative conventional CD workup, SBCE demonstrated a 32.5% incremental diagnostic yield, leading to therapy initiation based on severity.

Introduction

Many individuals rapidly regain excess weight once they stop dieting. This phenomenon, which is commonly called yoyo-dieting, is a pattern of losing weight and then regaining it, placing individuals at greater risk for metabolic complications and obesity. There is some evidence that yoyo-dieting-induced obesity causes long-term alterations in the gut microbiome composition. There is also increasing evidence suggesting that diets high in resistant starch (RS) may positively improve gut health and metabolism.

Aims & Methods

This study aimed to investigate how yoyo-dieting affects gut health and whether supplementation with resistant starch could be a promising and effective weight management strategy.
Male and female C57BL/6 mice (n=48/sex, n=8/group) were allocated to six different diets for 20 weeks [control, high-fat (HFD), yoyo-diet (HFD interspaced with control every 5 weeks), control with RS, HFD with RS, and yoyo-diet with RS]. Metabolic measurements were performed, including body weight, glucose and insulin tolerance tests, adipose tissue, and organ weight. Liver and intestines were collected for structural changes assessed by histology. Epithelial barrier integrity was assessed in Ussing chambers. Faecal samples were collected for microbial profiling using 16S ribosomal RNA sequencing.

Results

Male mice fed a HFD with RS had significantly lower weight gain, liver mass, adipose tissue, and insulin tolerance compared to mice fed a HFD alone, while no significant differences were observed in females. No significant differences in glucose tolerance and intestinal permeability were observed across all diets and between sexes. Male mice had significantly higher alpha diversity and a different microbiota profile compared to female mice. Mice fed diets supplemented with RS had significantly lower alpha diversity and a different microbiota profile compared to mice fed without RS. Male and female mice have different microbiota profiles. Mice fed a HFD with RS have a similar microbiota profile to mice fed the control diet with RS. After changing diets (switching from diets high in fat to the control diet – yoyo groups), no change in microbiome profile was observed in female mice previously fed HFD with RS, while male mice previously fed a HFD supplemented with RS had a similar microbiome profile to control mice.

Conclusion

Different microbiome signatures and metabolic measurements were observed in male and female mice. In male mice consuming a HFD, RS lowered weight gain and shifted the microbiota profile to one similar to mice fed a control diet with RS. In males consuming a HFD diet interspaced with the control diet (yoyo-diet), RS shifted the microbiota profile of mice to a similar signature seen in control animals. No significant differences were observed in females.

Disclosure

No conflict of interest