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Concept: Crohn's disease


Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

Concepts: Bacteria, Gut flora, Nutrition, Crohn's disease, Gastroenterology, Irritable bowel syndrome, Flatulence, Lactose intolerance


The appendix may modulate colon microbiota and bowel inflammation. We investigated whether appendectomy alters colorectal cancer risk.

Concepts: Cancer, Colorectal cancer, Ulcerative colitis, Crohn's disease, Colon, Constipation, Large intestine, Defecation



Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring.

Concepts: Immune system, Inflammation, Bacteria, Ulcerative colitis, Crohn's disease, Gastroenterology, Inflammatory bowel disease, Antibiotic


Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding “organic” conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.

Concepts: Ulcerative colitis, Crohn's disease, Gastroenterology, Inflammatory bowel disease, Irritable bowel syndrome, Coeliac disease, Diarrhea, Gastroenteritis


Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

Concepts: Immune system, Medicine, Bacteria, Ulcerative colitis, Crohn's disease, Colonoscopy, Gastroenterology, Inflammatory bowel disease


BACKGROUND: & Aims: The marijuana plant Cannabis sativa has been reported to produce beneficial effects for patients with inflammatory bowel diseases, but these have not been investigated in controlled trials. We performed a prospective trial to determine whether cannabis can induce remission in patients with Crohn’s disease. METHODS: We studied 21 patients (mean age 40±14 years, 13 male) with Crohn’s Disease and activity index (CDAI) scores >200 who did not respond to therapy with steroids, immunomodulators, or anti-tumor necrosis factor-α agents. Patients were randomly assigned to groups given cannabis, twice daily, in the form of cigarettes containing 11.5 mg of tetrahydrocannabinol (THC) or placebo containing cannabis flowers from which the THC had been extracted. Disease activity and laboratory tests were assessed during 8 weeks of treatment and 2 weeks thereafter. RESULTS: Complete remission (a CDAI score <150) was achieved by 5/11 subjects in the cannabis group (45%) and 1/10 in the placebo group (10%; P=.43). A clinical response (a decrease in CDAI score of >100) was observed in 10/11 subjects in the cannabis group (90%; from 330±105 to 152±109) and 4/10 in the placebo group (40%; from 373±94 to 306±143; P=.028). Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects. CONCLUSION: Although the primary endpoint of the study (induction of remission) was not achieved, a short course (8 week) of THC-rich cannabis produced significant clinical, steroid-free benefits to 11 patients with active CD, compared to placebo, without side effects. Further studies, with larger patient groups and a non-smoking mode of intake, are warranted. NCT01040910.

Concepts: Clinical trial, Ulcerative colitis, Crohn's disease, Inflammatory bowel disease, Placebo, Cannabis, Cannabis sativa


Patients with Crohn’s disease (CD) frequently complain of cognitive difficulties such as problems with concentration and clouding of thought, yet this has scarcely been objectively defined and underlying mechanisms remain unknown.

Concepts: Inflammation, Psychology, Osteoporosis, Medical terms, Crohn's disease, Corticosteroid, Inflammatory bowel disease, Abscess


In 2009, an estimated 565,000 Americans had Crohn’s disease (1), an inflammatory bowel disorder that can affect any part of the gastrointestinal tract. Symptoms include persistent diarrhea, abdominal cramps and pain, constipation leading to bowel obstruction, and rectal bleeding.* Symptoms sometimes intensify in severity and require hospitalization and surgeries of the small intestine, colon, or rectum (2). Hospital discharge data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) were used to estimate U.S. hospitalizations(†) for Crohn’s disease as both the first-listed and any-listed(§) discharge diagnosis and common surgical procedures during hospitalizations with Crohn’s disease as first-listed diagnosis from 2003 to 2013, the most recent decade of data. Despite new therapies that were expected to improve remission and reduce hospitalizations, estimated numbers (and age-adjusted rates per 100,000 U.S. population) of hospitalizations for Crohn’s disease as the first-listed diagnosis did not change significantly from 2003 to 2013. The proportion of these hospitalizations during which small bowel resection was performed decreased from 4.9% in 2003 to 3.9% in 2013 (p<0.05); however, colorectal resection and fistula repair rates remained stable. Hospital stays for any-listed Crohn's disease increased from >120,000 (44.2 per 100,000) in 2003 to >196,000 (59.7 per 100,000) in 2013 (p<0.05). Patient education initiatives should focus on increasing awareness of exacerbating factors and medication compliance to prevent hospitalizations.

Concepts: Ulcerative colitis, Crohn's disease, Colon, Abdominal pain, Large intestine, Gastroenterology, Small intestine, Bowel obstruction


Increasing incidence of inflammatory bowel diseases such as Crohn’s disease (CD) in developed nations is associated with changes to the environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the CD susceptibility geneNod2from intestinal abnormalities by inhibiting colonization with an inflammatoryBacteroidesspecies. Colonization resistance toBacteroideswas dependent on type-2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota, and that deworming treatment reduced Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis whereby certain individuals are genetically susceptible to the consequences of a changing microbial environment.

Concepts: Immune system, Disease, Bacteria, Ulcerative colitis, Crohn's disease, Gastroenterology, Inflammatory bowel disease, Helminthic therapy