Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Background: Rising rates of obesity have been reported in patients with inflammatory bowel disease (IBD); however, prospective data is lacking. The aim of this study is to prospectively evaluate body composition in adults with IBD over 24 months. Methods: Whole body dual energy X-ray absorptiometry (DXA) data was performed at 0 months, 12 months, and 24 months. Bone mineral density (BMD), fat mass index (FMI (kg)/height (m²)), appendicular skeletal muscle index (ASMI (kg)/height (m²)), visceral adipose tissue and the visceral adipose height index (VHI, VAT area (cm³)/height (m²)), and clinical and anthropometric assessments were performed at each time point. Multivariable linear mixed effects regression analyses were performed. Results: Initially, 154 participants were assessed at baseline (70% Crohn’s disease, 55% male, median age 31 years), of whom 129 underwent repeated DXA at 12 months, and 110 underwent repeated DXA at 24 months. Amongst those undergoing repeated DXA, their body mass index (BMI) significantly increased over time, such that by 24 months, 62% of patients were overweight or obese (annual change BMI β = 0.43, 95%CI = [0.18, 0.67], p = 0.0006). Gains in BMI related to increases in both FMI and VHI (β = 0.33, 95%CI = [0.14, 0.53], p = 0.0007; β = 0.08, 95%CI = [0.02, 0.13], p = 0.001; respectively), whereas ASMI decreased (β = −0.07, 95%CI = [−0.12, −0.01], p = 0.01) with a concordant rise in rates of myopenia (OR = 3.1 95%CI = [1.2, 7.7]; p = 0.01). Rates of osteopenia and osteoporosis were high (37%), but remained unchanged over time (p = 0.23). Conclusion: Increasing rates of obesity in patients with IBD coincide with decreases in lean muscle mass over time, while high rates of osteopenia remain stable. These previously undocumented issues warrant attention in routine care to prevent avoidable morbidity.

Visceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn’s disease (CD); however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes. Body composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm³]/height [m²] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease–related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed. Ninety-seven participants were assessed at baseline (55% male; median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to 3; P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3; 95% CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, –12; 95% CI, –19 to –4.5; P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL. VAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution–dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD.

Study aim: To assess the clinical outcomes of patients who received direct percutaneous endoscopic jejunostomy (DPEJ) for enteral feeding. Materials and methods: This is a 10-year cohort study in a single tertiary center. Main outcome measurements were technical success, and short- and long-term outcomes. DPEJ was attempted in 83 patients (51 men; 55 ± 2 years) for dysphagia (n = 35), gastroparesis with recurrent aspiration (n = 30), and levodopa drug infusion for severe Parkinson’s disease (n = 18). Results: DPEJ was successful in 75 (90 %) patients. All technical failures were related to the inability to find adequate trans-illumination, and were not influenced by BMI, age, gender, or indication. Peri-operative (30-day) adverse events occurred in 11 (13 %) patients, including wound infection (3), leakage around the stoma (4), minor bleeding requiring no intervention (2), and aspiration (1). There was one case (1.2 %) of gastric perforation after PEJ insertion for levodopa drug infusion trial. This 60-year-old woman required an emergency laparotomy with nil complications, and levodopa drug infusion recommenced successfully. One case of intestinal perforation (1.2 %) occurred after jejunostomy tube replacement at 6 months of insertion, which was successfully managed with surgery. There were no peri-operative deaths. Adequate delivery of enteral feeding or Duodopa drug was achieved in 66/73 (90 %) patients, with evidence of weight gain or improvement in Parkinson’s disease. Seven (8 %) continued to have clinical regurgitation but not aspiration. After a median follow-up of 84 months, 27 (33 %) patients died of their underlying diseases. Seven (8 %) had marked improvement in their underlying disease and had PEJ removed after 5 months (range 1 – 8 months). Limitations: Single center study. Conclusions: DPEJ is associated with a high technical success rate (90 %), a relatively low rate of peri-operative adverse events (13 %) and an improvement in long-term nutritional support in the majority of patients (90 %). DPEJ should be the procedure of choice to gain enteral access for feeding or drug delivery prior to considering surgery.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G₄ (FS-IgG₄) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG₄ in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG₄ titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG₄ (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG₄ and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG₄ to milk, wheat, soy, eggs, and nuts was significantly higher in EoE (P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG₄ to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 (P = 0.0007) and 1 (P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG₄ did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG₄ to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG₄ has potential as a noninvasive biomarker in EoE. When successful, FS-IgG₄–led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.