Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.

Clinical Characteristics and Treatment Response in Microscopic Colitis Based on Age at Diagnosis: A Multicenter Retrospective Study.

BACKGROUND: Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce. AIMS: To compare clinical characteristics and treatment response by age at diagnosis. METHODS: This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance. RESULTS: We included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m2, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07). CONCLUSIONS: There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.

Opioid Use Among Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Despite reported adverse effects of opioids in patients with inflammatory bowel disease (IBD), the burden of opioid use in this population appears to be high. We performed a systematic review and meta-analysis of prior studies to determine the prevalence of opioid use among patients with IBD as well as risk factors and outcomes associated with opioid use in this population. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Library through November of 2019. Primary outcomes included the prevalence of opioid use and demographic and clinical variables associated with opioid use in patients with IBD. Quality was assessed using the Newcastle-Ottawa scale. We used random-effect meta-analysis to estimate pooled relative risks (RRs) and 95% CIs. RESULTS: Of 780 citations identified, 31 were included in our study. The prevalence of opioid use was 21% (95% CI, 13%-30%) in the outpatient setting. Likewise, 62% (95% CI, 25%-92%) of patients received opioids while hospitalized for IBD. Opioid use was associated with female sex (RR 1.20; 95% CI 1.03-1.40), depression (1.99; 95% CI 1.80-2.19), substance abuse (4.67; 95% CI 2.87-7.60), prior gastrointestinal surgery (2.33; 95% CI 1.66-3.26), biologic use (1.36; 95% CI 1.06-1.74), and steroid use (1.41; 95% CI 1.04-1.91). Based on the systematic review, opioid use also appeared to be associated with increased IBD activity, healthcare use, infection, and mortality. CONCLUSION: In a systematic review and meta-analysis, we found that 21% of outpatients with IBD (and 62% of hospitalized patients) are opioid users; use is associated with more severe IBD and increased healthcare use. Further studies are required to determine whether opioids are the cause or an effect of these associations. Nonetheless, urgent interventions are needed to reduce opioid use, improve disease-related outcomes and reduce healthcare costs.

Microscopic Colitis Is Characterized by Intestinal Dysbiosis.

The critical role of the gut microbiome in microscopic colitis (MC) is evident by the observation that fecal diversion is associated with resolution of mucosal inflammation while restoration of fecal stream is associated with recurrence of disease.1 Characterization of the composition and function of the gut microbiome in MC therefore could provide insights into disease pathogenesis.