The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed ...shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.
Abstract Background In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. Methods We conducted a ...prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. Results During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard 325 mg tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval CI, 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week ( P trend < .001). Similar dose-response relationships were observed among short-term users (≤5 years; P trend <.001) and long-term users (>5 years; P trend <.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding ( P trend = .28). Conclusion Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users.
There is little evidence that adiposity associates with diverticulitis, especially among women. We conducted a comprehensive evaluation of obesity, weight change, and incidence of diverticulitis in a ...large cohort of women.
We conducted a prospective cohort study of 46,079 women enrolled in the Nurses’ Health Study who were 61–89 years old and free of diverticulitis, diverticular bleeding, cancers, or inflammatory bowel disease at baseline (in 2008). We used Cox proportional hazards models to examine the associations among risk of incident diverticulitis and body mass index (BMI), waist circumference, waist to hip ratio, and weight change from age 18 years to the present. The primary end point was first incident diverticulitis requiring antibiotic therapy or hospitalization.
We documented 1084 incident cases of diverticulitis over 6 years of follow-up, encompassing 248,001 person-years. After adjustment for other risk factors, women with a BMI ≥35.0 kg/m2 had a hazard ratio for diverticulitis of 1.42 (95% confidence interval CI, 1.08–1.85) compared to women with a BMI <22.5 kg/m2. Compared to women in the lowest quintile, the multivariable hazard ratios among women in the highest quintile were 1.35 (95% CI, 1.02–1.78) for waist circumference and 1.40 (95% CI, 1.07–1.84) for waist to hip ratio; these associations were attenuated with further adjustment for BMI. Compared to women maintaining weight from age 18 years to the present, those who gained ≥20 kg had a 73% increased risk of diverticulitis (95% CI, 27%–136%).
During a 6-year follow-up period, we observed an association between obesity and risk of diverticulitis among women. Weight gain during adulthood was also associated with increased risk.
Lower gastrointestinal bleeding is one of the most common gastrointestinal indications for hospital admission, particularly in the elderly. Diverticulosis accounts for up to 50% of cases, followed by ...ischemic colitis and anorectal lesions. Though most patients stop bleeding spontaneously and have favorable outcomes, long-term recurrence is a substantial problem for patients with bleeding from diverticulosis and angiodysplasia. The management of LGIB is challenging because of the diverse range of bleeding sources, the large extent of bowel involved, the intermittent nature of bleeding, and the various complicated and often invasive investigative modalities. Advances in endoscopic technology have brought colonoscopy to the forefront of the management of LGIB. However, many questions remained to be answered about its usefulness in routine clinical practice. More randomized controlled trials comparing available diagnostic strategies for LGIB are needed.
Diverticulosis is a common anatomical condition, which appears to be age-dependent. Individuals who develop chronic gastrointestinal symptoms or complications are referred to as having diverticular ...disease. Although the diagnosis of this condition can be relatively straightforward, randomized controlled trials are scarce and management often follows tradition rather than principles of evidence-based medicine. This report deals with the topics discussed during a symposium held during the United European Gastroenterology Week (Barcelona, October 2017). During the meeting, the role of dysbiosis in the pathogenesis of diverticular disease and its treatment were thoroughly discussed, by examining the efficacy and mechanisms of action of the currently used drugs. Recent studies have shown the presence of dysbiosis in patients with diverticular disease and suggest an imbalance in favor of bacteria with pro-inflammatory and pathogenetic potential. These microbiota changes correlate with mucosal immune activation, mirrored by a marked increase of macrophages in colonic mucosa, both in the diverticular region and at distant sites. The low-grade inflammation, driven by bacteria-induced immune activation, could be involved in the pathophysiology of symptoms. As a consequence, pharmacological approaches targeting enteric bacteria (with poorly absorbed antibiotics, like rifaximin, or probiotics) or intestinal inflammation (with 5-ASA derivatives or rifaximin) have shown capability of controlling symptoms and also preventing complications, albeit more research is needed to establish the optimal regimen (daily dose and duration) of therapy. Well-designed randomized-controlled trials (RCTs), including homogeneous populations of patients, are therefore needed. The future of management of many GI diseases, including symptomatic uncomplicated diverticular disease, will rely on the so-called ‘microbiota-directed therapies’.
Response to Fung et al Ma, Wenjie; Strate, Lisa L; Chan, Andrew T
The American journal of gastroenterology,
06/2020, Letnik:
115, Številka:
6
Journal Article
Much of what is known about the effects of alcohol and tobacco use on diverticular disease derives from studies of asymptomatic diverticulosis or complicated diverticulitis. We examined smoking and ...alcohol consumption and risk of incident diverticulitis in a large cohort of women.
We conducted a prospective study of 84,232 women in the Nurses' Health Study II (NHS II) who were 39-52 years old and without known diverticulitis at baseline in 2003. Smoking was ascertained every 2 years and alcohol use every 4 years. We used Cox proportional hazards regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs).
During 1,139,660 person-years of follow up, we identified 3018 incident cases of diverticulitis. After adjustment for other risk factors, current (HR, 1.20; 95% CI, 1.04-1.39) and past smoking (HR, 1.20; 95% CI, 1.11-1.30) were associated with increased risk of diverticulitis when compared with never smokers. Women who consumed ≥30 g/d of alcohol had a multivariate HR of 1.26 (95% CI, 1.05-1.50) when compared with women who did not drink. A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥15 g/d of alcohol were at highest risk of diverticulitis (multivariate HR, 1.60; 95% CI, 1.16-2.21), compared with participants who never smoked and reported no alcohol use.
In this large prospective study of women, smoking and alcohol consumption were associated with an increased risk of incident diverticulitis. These data highlight additional modifiable risk factors for diverticulitis that may aid in prevention.
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