Food Additives, a Key Environmental Factor in the Development of IBD through Gut Dysbiosis

Diet is a key environmental factor in inflammatory bowel disease (IBD) and, at the same time, represents one of the most promising therapies for IBD. Our daily diet often contains food additives present in numerous processed foods and even in dietary supplements. Recently, researchers and national authorities have been paying much attention to their toxicity and effects on gut microbiota and health. This review aims to gather the latest data focusing on the potential role of food additives in the pathogenesis of IBDs through gut microbiota modulation. Some artificial emulsifiers and sweeteners can induce the dysbiosis associated with an alteration of the intestinal barrier, an activation of chronic inflammation, and abnormal immune response accelerating the onset of IBD. Even if most of these results are retrieved from in vivo and in vitro studies, many artificial food additives can represent a potential hidden driver of gut chronic inflammation through gut microbiota alterations, especially in a population with IBD predisposition. In this context, pending the confirmation of these results by large human studies, it would be advisable that IBD patients avoid the consumption of processed food containing artificial food additives and follow a personalized nutritional therapy prescribed by a clinical nutritionist.

Inflammation in Focus: The Beginning and the End

The inflammation is an important biological response induced by various harmful stimuli, like viruses, bacterial infections, toxins, toxic compounds, tissue injury. During inflammation inflammatory cytokines and reactive oxygen species are produced. Inflammatory cytokines act on various receptors present on the plasma membrane of target cells. To initiate signaling cascade, and activate transcription factors, receptors should be internalized and enter the early endosomes, where the members of the signaling cascade can meet. The further cytoplasmic fate of the receptor plays crucial role in the progression and the course of inflammation. Usually acute inflammation removes injurious stimuli and helps to regain the normal healthy status of the organism. In contrast to this the uncontrolled chronic inflammation—stimulating other than immune cells, inducing transdifferentiation—can provide base of various serious diseases. This paper draws the attention of the long-lasting consequence of chronic inflammation, pointing out that one of the most important step in medication is to identify in time the factors initiating and maintaining inflammation.

Canine transmissible venereal tumour established in immunodeficient mice reprograms the gene expression profiles associated with a favourable tumour microenvironment to enable cancer malignancy

Background Canine transmissible venereal tumours (CTVTs) can cross the major histocompatibility complex barrier to spread among dogs. In addition to the transmissibility within canids, CTVTs are also known as a suitable model for investigating the tumour–host immunity interaction because dogs live with humans and experience the same environmental risk factors for tumourigenesis. Moreover, outbred dogs are more appropriate than inbred mice models for simulating the diversity of human cancer development. This study built a new model of CTVTs, known as MCTVTs, to further probe the shaping effects of immune stress on tumour development. For xenotransplantation, CTVTs were first injected and developed in immunodeficient mice (NOD.CB17-Prkdcscid/NcrCrl), defined as XCTVTs. The XCTVTs harvested from NOD/SCID mice were then inoculated and grown in beagles and named mouse xenotransplantation of CTVTs (MCTVTs). Results After the inoculation of CTVTs and MCTVTs into immune-competent beagle dogs separately, MCTVTs grew faster and metastasized more frequently than CTVTs did. Gene expression profiles in CTVTs and MCTVTs were analysed by cDNA microarray to reveal that MCTVTs expressed many tumour-promoting genes involved in chronic inflammation, chemotaxis, extracellular space modification, NF-kappa B pathways, and focal adhesion. Furthermore, several well-known tumour-associated biomarkers which could predict tumour progression were overexpressed in MCTVTs. Conclusions This study demonstrated that defective host immunity can result in gene instability and enable transcriptome reprogramming within tumour cells. Fast tumour growth in beagle dogs and overexpression of tumour-associated biomarkers were found in a CTVT strain previously established in immunodeficient mice. In addition, dysregulated interaction of chronic inflammation, chemotaxis, and extracellular space modification were revealed to imply the possibly exacerbating mechanisms in the microenvironments of these tumours. In summary, this study offers a potential method to facilitate tumour progression and provide a niche for discovering tumour-associated biomarkers in cancer research.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). Methods Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. Results DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0–57.6 vs. 20.6 months, 95% CI 10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19–9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02–2.16], lymph node metastases N1–2 (HR 1.71, 95% CI 1.16–2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). Conclusions Our results indicate that the pancreatic stroma is associated with PDAC patients’ DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Combined royal jelly 10-hydroxydecanoic acid and aspirin is synergistic against memory deficit and neuroinflammation

Alzheimer’s disease (AD), the most common form of neurodegenerative dementia among the older population, is associated with acute or chronic inflammation. As a nonsteroidal anti-inflammatory drug, aspirin has recently been...

Accurate and rapid microfluidic ELISA to monitor Infliximab titers in patients with inflammatory bowel diseases

Inflammatory bowel disease (IBD) is a term used to describe disorders that involve chronic inflammation in the gastrointestinal tract, affecting more than 6.8 million people worldwide.1 Biological therapy is used...