Background & Aims In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Methods Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average of 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Results Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P<.05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P<.05) and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. Conclusions After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous group of liver diseases characterized by the accumulation of fat in the liver. The heterogeneity of NAFLD is reflected in a clinical and histologic spectrum where some patients develop isolated steatosis of the liver, termed nonalcoholic fatty liver, whereas others develop hepatocyte injury, ballooning, inflammation, and consequent fibrosis, termed nonalcoholic steatohepatitis (NASH). Systemic insulin resistance is a major driver of hepatic steatosis in NAFLD. Lipotoxicity of accumulated lipids along with activation of the innate immune system are major drivers of NASH. Lipid‐induced sublethal and lethal stress culminates in the activation of inflammatory processes, such as the release of proinflammatory extracellular vesicles and cell death. Innate and adaptive immune mechanisms involving macrophages, dendritic cells, and lymphocytes are central drivers of inflammation that recognize damage‐ and pathogen‐associated molecular patterns and contribute to the progression of the inflammatory cascade. While the activation of the innate immune system and the recruitment of proinflammatory monocytes into the liver in NASH are well known, the exact signals that lead to this remain less well defined. Further, the contribution of other immune cell types, such as neutrophils and B cells, is an area of intense research. Many host factors, such as the microbiome and gut–liver axis, modify individual susceptibility to NASH. In this review, we discuss lipotoxicity, inflammation, and the contribution of interorgan crosstalk in NASH pathogenesis.

Background & Aims Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population. Methods Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980–2007 in Olmsted County, Minnesota. Results In 1980–1989 the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000–2007 (P<.001). Incidence increased with age (P<.001); however, the temporal increase was greater in younger people (P<.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio [HR] per decade 0.63; 95% confidence interval [CI], 0.59–0.66) and women (HR 0.68; 95% CI, 0.58–0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<.001). Age was associated with increased risk of local (odds ratio [OR] 1.27 per decade; 95% CI, 1.04–1.57) and systemic (OR 1.83; 95% CI, 1.20–2.80) complications. Survival after diverticulitis was lower in older people (P<.001) and men (P<.001) and worsened over time (P<.001). The incidence of surgery for diverticulitis did not change from 1980–2007. Conclusions The incidence of diverticulitis has increased by 50% in 2000–2007 compared to 1990–1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis had less severe disease, more recurrence, and better survival.