Curcumin diffuses through cell membranes into the endoplasmic reticulum, mitochondria, and nucleus, where it exerts actions, as an antioxidant property. Therefore, its use has been advocated for chemopreventive, antimetastatic, and anti-angiogenic purposes. We conducted a literature review to summarize studies investigating the relationship between curcumin and colorectal cancer (CRC). In vitro studies, performed on human colon cancer cell lines, showed that curcumin inhibited cellular growth through cycle arrest at the G2/M and G1 phases, as well as stimulated apoptosis by interacting with multiple molecular targets. In vivo studies have been performed in inflammatory and genetic CRC animal models with a chemopreventive effect. To improve curcumin bioavailability, it has been associated with small particles that increase its absorption when orally administered with excellent results on both inflammation and carcinogenesis. Curcumin has been used, moreover, as a component of dietetic formulations for CRC chemoprevention. These combinations showed in vitro and in vivo anticarcinogenetic properties in inflammation-related and genetic CRC. A synergic effect was suggested using an individual constituent dosage, which was lower than that experimentally used “in vivo” for single components. In conclusion, curcumin falls within the category of plant origin substances able to prevent CRC in animals. This property offers promising expectations in humans.

Giuseppe Losurdo, Gioacchino Leandro, Enzo Ierardi, Francesco Perri, Michele Barone, Mariabeatrice Principi, and Alfredo Di Leo. J Neurogastroenterol Motil 1999;0:. https://doi.org/10.5056/jnm19113

Background & Aims: Escherichia coli Nissle 1917 (EcN) has been recommended as a therapeutic tool for ulcerative colitis (UC) treatment. However, to date, no meta-analysis has been performed on this topic. Methods: We performed a literature search on PubMed, MEDLINE, Science Direct and EMBASE. We evaluated success rates for induction of remission, relapse rates and side effects, expressed as Intention-To-Treat. Odd ratios (OR), pooled OR and 95% confidence intervals (CI) were calculated, based on the Mantel-Haenszel method. Heterogeneity was assessed by using the χ2 and I2 statistics and, if present, a random-effects model was adopted. Results: We selected six eligible trials, with 719 patients, 390 assigned to the study group and 329 to the control group. EcN induced remission in 61.6% of cases, while in the control group (mesalazine) the remission was achieved in 69.5% of cases, with a mean difference of 7.9%. The pooled OR was 0.92 (95% CI 0.15-9.66, p=0.93). A single study showed a better performance of EcN than the placebo. A relapse of the disease occurred in 36.8% in the EcN group and in 36.1% in the control group (mesalazine), with a mean difference of 0.8%, OR=1.07, with a 95% CI of 0.70-1.64 (p=0.74). Side effects were comparable (OR=1.44, 95% CI 0.80-2.59, p=0.22). Conclusions: EcN is equivalent to mesalazine in preventing disease relapse, thus confirming current guideline recommendations. EcN seems to be as effective as controls in inducing remission and therefore, its use cannot be recommended as in one study the comparison was performed against placebo. Further studies may be helpful for this subject. Abbreviations: EcN: Escherichia coli Nissle; UC: ulcerative colitis; IBD: inflammatory bowel disease; CD: Crohn’s disease; ITT: intention-to-treat.

Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists. However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC). Therefore, the World Health Organization (WHO) classification has identified four categories of serrated lesions: hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenoma (TSAs) and unclassified serrated adenomas. SSLs with dysplasia and TSAs are the most common precursors of CRC. CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC. Unlike CRCs arising through the adenoma–carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.

Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the "ideal therapy", paradoxically, appears to be a "utopia", despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.