Gastrointestinal Disorders

Colorectal cancer (CRC) is one of the most common cancers and represents a major global health burden. While genetics are implicated in a portion of CRC patients, most cases are sporadic. A new possibility of tumor initiation and promotion might be microbiome composition. It was recently shown that bacteria from the gut microbiome might be used as biomarkers for CRC detection, especially Fusobacterium nucleatum, Peptostreoptococcus stomatis, Parvimonas mica, Solobacterium moorei, and Peptostreptococcus anaerobius. Conversely, the healthy gut microbiome is mostly colonized by Bacterioides (Bacterioides fragilis, vulgatus, uniformis), Firmicutes (Clostridium spp., Ruminococcus faecis, Enterococcus faecium), and Actinobacteria (Bifidobacterium bifidum). Some strains of gut bacteria favor tumor promotion through DNA and RNA damage (directly or through interaction with other known food carcinogens) and through local immune inhibition. It is possible that bacteria (e.g., Bacillus polyfermenticus, Alistipes shahii, Lactobacillus casei) exist with protective functions against tumor promotion. Despite current advances in colorectal cancer treatment, especially in the medical oncology and radiotherapy domains, surgery remains the mainstay of curative treatment for colorectal cancer patients, even in the oligometastatic setting. Surgical complications like anastomotic leakage, excessive blood loss, abscess, and abdominal sepsis can reduce 1-year and 5-year overall survival and increase the recurrence rates for these patients; therefore, we reviewed currently published data focusing on the relationship between gut microbiota and postoperative complications for colorectal cancer patients. Full article

Idiopathic achalasia is a motility disorder affecting the lower esophageal sphincter. Dysphagia is a hallmark symptom, but patients may exhibit other symptoms. The aim of this review is to compare achalasia symptoms globally. PubMed and Google Scholar were filtered from 1952–2021 with the search terms achalasia, epidemiology, diet, countries, and genetics. A total of 14 articles addressed demographics, symptom profiles, genetics, and diagnosis criteria amongst 2463 patients. Data on countries’ climate and diet were obtained through Arc Geographic Information System (GIS) and Our World in Data. Countries were grouped by similar climate zones and diets. Achalasia symptoms varied by region. In West Africa, patients exhibit parotid swelling, anemia, and dehydration; diminished appetite in East Asia; dysphagia and weight loss in West Asia and Europe; respiratory symptoms, reflux, and retrosternal pain in North America; and vomiting in Southern Asia. Weighted percentages of dietary oils/fats were (24.3%) in North America, Western Asia (17.8%); Europe (17.7%); East Asia (17.6%); West Africa (14.7%); Southern Asia (13.8%); North Africa (12.4%); Northeast Africa (10.1%). Conditions such as Down Syndrome and Triple A syndrome are associated with achalasia. There was no correlation for achalasia presentation and climate zones. Achalasia symptoms are likely multifactorial. Diet, genetics, and environmental factors may play significant roles. Full article

The management of IBD is highly complex, given the heterogeneity of treatment plans for an equally diverse patient population. Given the intricacy of treatment, improved health literacy may be associated with better outcomes. Methods: Patients were assessed before and after their endoscopy and for their knowledge of their disease status, their correct recall of the endoscopy results, their provider–patient communication, and communication preferences. Results: A total of 37 patients completed both surveys and were included in the final analysis. The median age was 45 years. The median number of years diagnosed with IBD was 13. Most patients correctly recalled the results of their surveillance endoscopy after their procedure (84%). Many patients (65%) felt they were equally involved in the decision making process in regard to their surveillance endoscopies. Most patients (92%) reported having results clearly explained to them. Most patients (76%) preferred receiving an email or patient message with results, and 69% of patients reported receiving results in the way they preferred. Conclusions: Most of the patients with IBD who were surveyed had adequate knowledge of their disease process and could accurately recall the results of their endoscopy. However, the delivery of health information can be optimized, as nearly one-third of our patients did not receive their endoscopy results in their preferred method. Full article

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, functional constipation, and functional dyspepsia, have had a high prevalence over the past few years. Recent evidence suggests that functional foods and bioactive compounds, such as probiotics and phytochemicals, may have a positive effect in treating the symptoms of the above diseases. In this systematic review study, 32 published studies were selected with the use of comprehensive scientific databases, according to PRISMA guidelines, with emphasis on recent interventional studies that reflect the effect of probiotics and selected phytochemicals on the improvement of FGID symptoms. The bioactive compounds in the selected studies were administered to patients either in capsule form or in enriched food products (yogurt, juice, etc.). According to the results, there is a correlation between the consumption of probiotics and phytochemicals, such as polyphenols, and the relief of symptoms in selected gastrointestinal disorders. Enriching foods that are regularly consumed by the population, such as fruit juices, yogurt, and cheese, with ingredients that may have a positive effect on gastrointestinal disorders, could be a possible novel goal for the management of these diseases. However, further evidence is required for the role of probiotics and phytochemicals in FGIDs to be fully understood. Full article

This paper reviews the tools available to assess outcomes of treatment in irritable bowel syndrome, especially the effect on abdominal pain. Tools were identified through a wide-ranging scrutiny of PubMed and Google Scholar, together with a review of further references quoted in those publications. It critically considers their development, relevance and reliability. The Irritable Bowel Severity Scoring System (IBS-SSS) was the first simple method of monitoring the progress of the disease and its treatment. It led on to other instruments, such as The Irritable Bowel Syndrome Quality of Life (IBS-QOL). It is easier to read and faster to complete than the IBS-SSS., However, these and other tools were developed for English speaking populations. This review considers the impact of ethnicity and gender, together with the lack of information on the effect of age on the potential validity of these tools in other populations. Issues with the adequacy and appropriateness of translations of such tools are discussed. The overall conclusion is that there are few tools which meet the criteria necessary to place confidence in their validity as appropriate measures of patient outcomes. Full article

Patients with advanced liver disease who are not taking vitamin K antagonists often have an elevated international normalized ratio, potentially due to vitamin K deficiency and the decreased synthesis of clotting factors by the liver. It is possible that vitamin K deficiency is due to dietary deficiency, impaired absorption in the small intestine, or both. This has led to the practice of the administration of phytonadione to limit the risks of bleeding in these patients. However, phytonadione is available in different formulations with varying pharmacokinetics and there is a paucity of data in the literature to guide optimal management. The routine use of phytonadione to correct INR in cirrhotic patients not taking warfarin should be avoided due to the lack of proven benefits. However, intravenous phytonadione may be considered in actively bleeding or critically ill patients with vitamin K deficiency. Oral formulation is unlikely to be absorbed in cirrhotic patients and should be avoided. Full article

Over the last decade, there have been a number of studies which have documented disparate levels of care in the management of inflammatory bowel disease amongst various minority communities in the UK. Similar findings had previously been described in the USA, where access to biologics has been an issue. In this study, data on admissions to hospital of South Asian and White British patients with inflammatory bowel disease between 2015 and 2019 were collected from 12 National Health Service (NHS) trusts in England, three Health Boards in Wales and two Scottish health organizations using Freedom of Information requests. The analyses of data were based on the assumption that inflammatory bowel disease (IBD) has the same prevalence in the South Asian community and the White British community in the UK. Comparisons were made between the proportion of hospitalised patients who were South Asian and the proportion who were White British in the local community using a z statistic. In Leicester, Bradford, Croydon and Lothian, the proportion of patients from the South Asian community admitted to hospital was significantly greater than the proportion from the local White British community, which is consistent with the greater frequency and severity of the disease in the South Asian community in the UK. However, in Coventry, Wolverhampton, Walsall, Acute Pennine Trust in the north-west of England, Barking, Havering and Redbridge and Glasgow, South Asian patients were significantly under-represented, indicating significant issues with access to hospital-based healthcare for inflammatory bowel disease. This study provides evidence of on-going evidence of disparate levels of care for patients from a South Asian background, with inflammatory bowel disease being underserved by a number of NHS Trusts, Health Boards and comparable organisations. When there is on-going failure to achieve the objectives of the NHS of achieving equality in the delivery of care, it is critical to introduce effective policies which will alter the in-built inertia to change within such organisations. Full article

Background: Disaccharidase (DS) deficiencies have been reported in pediatric patients with inflammatory bowel disease (IBD), but the relationship between duodenal inflammation and DS deficiency has not been evaluated outside of lactase deficiency. Methods: This study assessed DS levels and DS deficiencies in pediatric IBD patients who underwent endoscopy with assessment of DS activity. Records were reviewed for IBD subtype, pathology findings, and the results of DS analysis. Results: A total of 136 patients were identified. Overall, 89 (65.4%) patients had a diagnosis of Crohn’s disease (CD), 31 (22.8%) patients had a diagnosis of ulcerative colitis (UC), and 16 (11.8%) patients had a diagnosis of indeterminant colitis. Lactase deficiency was identified in 55.9% of patients, followed by maltase deficiency (19.9%), sucrase and palatinase deficiency (14%), and pan-deficiency (12.5%). When analyzing only patients with CD, patients with duodenitis were more likely to exhibit sucrase deficiency, palatinase deficiency, and pan-deficiency with a trend towards maltase deficiency. Conclusions: The most common DS deficiency was lactase deficiency; however, this was not related to duodenal inflammation. Pediatric patients with CD and duodenal inflammation exhibit DS deficiencies, namely, sucrase, palatinase, and pan-deficiency. Dietary adjustments may be warranted temporarily until duodenal inflammation is healed in patients with CD and duodenitis. Full article

Celiac disease (CD) is a small intestinal inflammatory condition where consumption of gluten induces a T-cell mediated immune response that damages the intestinal mucosa in susceptible individuals. CD affects at least 1% of the world’s population. The increasing prevalence of CD has been reported over the last few decades. However, the reason for this increase is not known so far. Certain factors such as increase in awareness and the development of advanced and highly sensitive diagnostic screening markers are considered significant factors for this increase. Wheat breeding strategies, fertilizers, and pesticides, particularly herbicides, are also thought to have a role in the increasing prevalence. However, less is known about this issue. In this review, we investigated the role of these agronomic practices in depth. Our literature-based results showed that wheat breeding, use of nitrogen-based fertilizers, and herbicides cannot be solely responsible for the increase in celiac prevalence. However, applying nitrogen fertilizers is associated with an increase in gluten in wheat, which increases the risk of developing celiac-specific symptoms in gluten-sensitive individuals. Additionally, clustered regularly interspaced short palindromic repeats (CRISPR) techniques can edit multiple gliadin genes, resulting in a low-immunogenic wheat variety that is safe for such individuals. Full article

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease. Full article

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death due to cancer in the world. Therefore, the identification of novel druggable targets is urgently needed. Tribbles proteins belong to a pseudokinase family, previously recognized in CRC as oncogenes and potential therapeutic targets. Here, we analyzed the expression of TRIB1, TRIB2, and TRIB3 simultaneously in 33 data sets from CRC based on available GEO profiles. We show that all three Tribbles genes are overrepresented in CRC cell lines and primary tumors, though depending on specific features of the CRC samples. Higher expression of TRIB2 in the tumor microenvironment and TRIB3 overexpression in an early stage of CRC development, unveil a potential and unexplored role for these proteins in the context of CRC. Differential Tribbles expression was also explored in diverse cellular experimental conditions where either genetic or pharmacological approaches were used, providing novel hints for future research. This comprehensive bioinformatic analysis provides new insights into Tribbles gene expression and transcript regulation in CRC. Full article

Tumor-associated macrophages (TAMs) may be noticed in gastric carcinomas (GC), but their clinicopathological significance has not been yet explored. From a histological review of 400 cases of tubular/papillary adenocarcinomas, 24 cases of stage I–II gastric adenocarcinomas with intraglandular and stromal TAMs were identified. Their clinicopathological features were compared with 72 pT-matched as well as stage-matched control cases of adenocarcinomas without TAMs. TAMs present in GC cases were present either in glands or in neoplastic stroma, showing an immunoreactivity for CD68 and CD80; sometimes, they were organized in mature granulomas with occasional giant cells. Therefore, the stained TAMs were reminiscent of a specific polarized macrophage M1 phenotype; however, in any case of our cohort, no M2 phenotype macrophages were documented by CD 163 and CD 204 immunostainings. Statistically, no significant differences in age, gender, tumor location, size, and lymphovascular and perineural invasion between the case group with TAMs and pT- as well as stage-matched controls were reported; furthermore, the case group showed lower frequency of lymph node metastasis (p = 0.02). In addition, a significantly different clinical course and overall survival rate were also observed in gastric adenocarcinomas with M1 TAMs (p = 0.02) in comparison to controls. These results suggest that tumor-associated M1 macrophages are related to a quite indolent growth and a better prognosis of patients with this peculiar variant of gastric adenocarcinomas. Full article

Despite the recognized benefits of colorectal cancer (CRC) screening, uptake is still suboptimal in many countries. In addressing this issue, one important element that has not received sufficient attention is population preference. Our review provides a comprehensive summary of the up-to-date evidence relative to this topic. Four OVID databases were searched: Ovid MEDLINE^® ALL, Biological Abstracts, CAB Abstracts, and Global Health. Among the 742 articles generated, 154 full texts were selected for a more thorough evaluation based on predefined inclusion criteria. Finally, 83 studies were included in our review. The general population preferred either colonoscopy as the most accurate test, or fecal occult blood test (FOBT) as the least invasive for CRC screening. The emerging blood test (SEPT9) and capsule colonoscopy (nanopill), with the potential to overcome the pitfalls of the available techniques, were also favored. Gender, age, race, screening experience, education and beliefs, the perceived risk of CRC, insurance, and health status influence one’s test preference. To improve uptake, CRC screening programs should consider offering test alternatives and tailoring the content and delivery of screening information to the public’s preferences. Other logistical measures in terms of the types of bowel preparation, gender of endoscopist, stool collection device, and reward for participants can also be useful. Full article

The reduction of excessive weight remains a major public health challenge, with control currently limited to a calorie reduction strategy. Currently, attempts are being made at revisiting the fibre hypothesis based on the African studies of Denis Burkitt, that the lack of dietary fibre in the modern diet was responsible for the occurrence of obesity and many of the other non-communicable diseases of what he called “Western civilization”. However, the dilemma is that Burkitt himself stressed that other peoples of his day, such as the Maasai, remained healthy without consuming such high fibre diets. Equally, the present obesity epidemic is accompanied by diseases of a malfunctioning immune system and of poor mental health that do not seem to be adequately explained simply by a deficiency of dietary fibre. Though unknown in Burkitt’s day, an increasing degradation of a mutualistic intestinal microbiome would offer a better fit to the observed epidemiology, especially if the microbiome is not effectively passed on from mother to child at birth. Taking the broader view, in this article we posit a view of the microbiome as a cofactor of mammalian evolution, in which a maternal microbial inheritance complements the parental genetic inheritance of the animal, both engaging epigenetic processes. As this would require the microbiome to be fully integrated with the animal as it develops into an adult, so we have a meaningful evolutionary role for the microbiome–gut–brain axis. By a failure to correctly establish a microbiome–gut interface, the inhibition of maternal microbial inheritance sets the scene for the future development of non-communicable disease: compromised immune system function on the one hand and dysfunctional gut–brain communication on the other. The basic principle is that the fully functioning, diverse, microbiome achieves interkingdom communication by the generation of messenger chemicals, semiochemicals. It is envisaged that the in situ detection of these as yet ill-defined chemical entities by means of an ingestible sensor would indicate the severity of disease and provide a guide as to its amelioration. Full article

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response. Full article

Infectious Diseases Incorporated (IDI) is an infectious disease think-tank, established in 1973. Crohn’s disease (CD) is a chronic, recurrent disease of the gastrointestinal tract that has reached epidemic proportions within industrialized nations. CD is said to be without cure. Since 2003, therapeutic interventions have focused on disruption of the pro-inflammatory Th1 response against an unknown antigen. In 2015, the Hruska Postulate was introduced and, in so doing, explained how, in the absence of acquired immunity, newborn infection by Mycobacterium avium subspecies paratuberculosis could cause fixation of the immune system’s Th1 response against the organism. The Hruska Postulate was utilized to answer all the documented epidemiological facts embedded in the natural history of Crohn’s disease and, in particular, why breastfeeding confers protection against the future development of Crohn’s disease. It is Infectious Diseases Incorporated’s (IDI) stated opinion that Crohn’s disease is both preventable and curable if treated appropriately in its early stages. Full article

The incidence of inflammatory bowel diseases, such as Crohn’s disease (CD), is increasing worldwide. Despite several new therapeutics to treat CD, many patients fail to respond to their medications and inevitably face surgical resection. While genetics plays a role in CD, environmental factors are potential triggers. Recent research from the past few years suggest that pro-inflammatory foods are associated with an increased risk of CD. Some studies have shown the benefit of including exclusion diets, such as the specific carbohydrate diet (SCD) and exclusive elemental diets, to induce CD remission, but published data is limited. This case study explores how an exclusive elemental and exclusion diet helped induce clinical and biochemical remission and radiologic healing in a young adult male who had failed to achieve remission using standard medical treatment. C-reactive protein (CRP), fecal calprotectin, and magnetic resonance enterography (MRE) served as objective markers of inflammation in this study. Full article