Ultra-processed foods and food additives in gut health and disease.

Ultra-processed foods (UPFs) and food additives have become ubiquitous components of the modern human diet. There is increasing evidence of an association between diets rich in UPFs and gut disease, including inflammatory bowel disease, colorectal cancer and irritable bowel syndrome. Food additives are added to many UPFs and have themselves been shown to affect gut health. For example, evidence shows that some emulsifiers, sweeteners, colours, and microparticles and nanoparticles have effects on a range of outcomes, including the gut microbiome, intestinal permeability and intestinal inflammation. Broadly speaking, evidence for the effect of UPFs on gut disease comes from observational epidemiological studies, whereas, by contrast, evidence for the effect of food additives comes largely from preclinical studies conducted in vitro or in animal models. Fewer studies have investigated the effect of UPFs or food additives on gut health and disease in human intervention studies. Hence, the aim of this article is to critically review the evidence for the effects of UPF and food additives on gut health and disease and to discuss the clinical application of these findings.

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study.

Objective: Ustekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness of ustekinumab in UC in a real-world setting. Design/method: This was a multicentre, retrospective, observational cohort study between February 2020 and January 2022. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical remission was defined as a SCCAI≤2. The primary endpoints were rates of corticosteroid-free remission (CSFR) at week 16 and at week 26. Objective outcomes, including faecal calprotectin (FCAL), were also collected. Results: 110 patients with UC (65% male; median age 40 (IQR range 29-59); 96% with prior biologic and/or tofacitinib exposure) had a median follow-up of 28 weeks (IQR 17-47). CSFR was 36% (18/50) at week 16% and 33% (13/39) at week 26, corresponding with a significant fall in SCCAI from 6 (IQR 4-8) at baseline to 3 (IQR 0-5) at week 26, p<0.001. By week 16, there was improvement of median FCAL measurements, which fell from a baseline of 610 µg/g (IQR 333-1100) to 102 µg/g (IQR 54-674) at week 16. At the end of follow-up, 15% (17/110) had discontinued treatment; 13 patients due to primary non-response or loss of response, and 1 patient for family planning. Treatment was discontinued in three patients due to adverse events. Conclusion: In the largest real-world study to date, ustekinumab was effective with a reassuring safety profile in a refractory cohort of patients.

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab.

Background: Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4ß7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting. Methods: Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period. Results: Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001). Conclusion: Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Food Additive Emulsifiers and Their Impact on Gut Microbiome, Permeability, and Inflammation: Mechanistic Insights in Inflammatory Bowel Disease.

The global burden of inflammatory bowel disease [IBD] has increased over the 21st century. Despite multiple studies investigating the pathogenesis of IBD, the causative mechanisms pertaining to its increased prevalence remain unclear. There is growing evidence that aspects of a 'Western diet' increase the risk of developing IBD. More recently, evidence implicating dietary emulsifiers has accumulated, with ecological studies showing a positive correlation between inflammatory bowel disease and emulsifier consumption. Further to these, cell and animal studies have demonstrated plausible mechanisms by which dietary emulsifiers may contribute to IBD pathogenesis through mechanisms including: promotion of pro-inflammatory intestinal microbiota; disruption of mucus architecture; increased intestinal permeability; activation of inflammatory pathways; and disruption of the cell cycle. This review critically analyses the current evidence for these mechanisms that may be of pathological relevance to IBD, evaluates recent dietary trials, acknowledges the challenges of dietary intervention studies, and gives an overview of ongoing and future clinical trials in this important area.

Impact of the coronavirus infectious disease (COVID-19) pandemic on the provision of inflammatory bowel disease (IBD) antenatal care and outcomes of pregnancies in women with IBD.

BACKGROUND: The impact of COVID-19 on pregnant inflammatory bowel disease (IBD) patients is currently unknown. Reconfiguration of services during the pandemic may negatively affect medical and obstetric care. We aimed to examine the impacts on IBD antenatal care and pregnancy outcomes. METHODS: Retrospective data were recorded in consecutive patients attending for IBD antenatal care including outpatient appointments, infusion unit visits and advice line encounters. RESULTS: We included 244 pregnant women with IBD, of which 75 (30.7%) were on biologics in whom the treatment was stopped in 29.3% at a median 28 weeks gestation. In addition, 9% of patients were on corticosteroids and 21.5% continued on thiopurines. The care provided during 460 patient encounters was not affected by the pandemic in 94.1% but 68.2% were performed via telephone (compared with 3% prepandemic practice; p<0.0001). One-hundred-ten women delivered 111 alive babies (mean 38.2 weeks gestation, mean birth weight 3324 g) with 12 (11.0%) giving birth before week 37. Birth occurred by vaginal delivery in 72 (56.4%) and by caesarean section in 48 (43.6%) cases. Thirty-three were elective (12 for IBD indications) and 15 emergency caesarean sections. Breast feeding rates were low (38.6%). Among 244 pregnant women with IBD, 1 suspected COVID-19 infection was recorded. CONCLUSION: IBD antenatal care adjustments during the COVID-19 pandemic have not negatively affected patient care. Despite high levels of immunosuppression, only a single COVID-19 infection occurred. Adverse pregnancy outcomes were infrequent.

Delayed diagnosis of lymphogranuloma venereum-associated colitis in a man first suspected to have rectal cancer.

Lymphogranuloma venereum-associated colitis is a diagnosis that should not be missed. The following case represents the importance of a thorough history, including the importance of the sexual history to prevent the misdiagnosis of these patients.

Eosinophilic oesophagitis.

Eosinophilic oesophagitis is a chronic immune-mediated inflammatory disorder of the oesophagus, characterized by symptoms of dysphagia or food bolus obstruction. Diagnosis is supported by typical histological findings. This article covers pertinent aspects of the disease, pathogenic explanations and treatment options.

The Role of Vitamin D in Inflammatory Bowel Disease.

Vitamin D is known to be vital in maintaining bone health, mineralisation and for fracture prevention. It has also been implicated in a number of autoimmune diseases and has therefore been studied for its potential role in Inflammatory Bowel Disease (IBD). This review looks at the current literature on the role of vitamin D and its potential role as an immunomodulator, disease modifier and bone health in IBD patients. There is substantial supporting evidence of an important role from epidemiological, genetic and immunological studies, but there is also conflicting evidence and nothing proving to be definitive from clinical studies. There are also a number of confounders with IBD patients, as their lifestyles and medications may affect vitamin D levels. Murine studies have added vast amounts to our knowledge of vitamin D and its antimicrobial role, as well as its effect on immune cell proliferation other inflammatory molecules, such as Tumour Necrosis Factor-α (TNFα). It is clear that larger trials investigating the effects of oral supplementation of vitamin D in IBD patients are necessary.

Ethnicity differences in genetic susceptibility to ulcerative colitis: a comparison of Indian asians and white northern Europeans.

BACKGROUND: Studies in Caucasian populations have identified a number of genetic associations with ulcerative colitis (UC), but reports from other ethnic groups have been limited. Recent studies from India have reported an association with UC and a single polymorphism (SNP) in CARD15/NOD2 (SNP5, rs2066842), which has not been reported in Caucasian UC cohorts. In addition, strong genetic associations with SNPs in the HLA region have been reported in Indian UC populations. However, there have been no reports on the frequency of HLA class II alleles in Indian populations with inflammatory bowel disease to examine whether the associations differ from other ethnic populations. METHODS: Genotyping was performed for 137 Indian UC patients for HLA class II alleles (HLA-DRB1*1502 & HLA-DRB1*0103), IL23R (rs11209026), and CARD15/NOD2 (rs2066842). The genetic data were compared with 204 healthy Indian controls and 50 white European UC patients. RESULTS: The HLA-DRB1*0103 allele was absent in all Indian UC patients and controls in contrast to white European UC patients (9/50: 18%). The HLA-DRB1*1502 allele was significantly more frequent in the Indian UC cohort (29.2%) than controls (17.6%) (P = 0.04) and the allele was absent in the white European cohort. There were no significant differences in the frequency of the CARD15/NOD2 (rs2066842) variant or IL23R (rs11209026) between the different ethnic groups. CONCLUSIONS: The HLA-DRB1*0103 allele is rare or absent in the Indian Asian population but HLA-DRB1*1502 is positively associated with UC. Further genetic studies in this population could provide valuable information and may help distinguish the degree of influence of genetic and environmental pathogenic factors.