The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.

BACKGROUND & AIMS: Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. METHODS: In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n = 15) or placebo (n = 15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. RESULTS: Short term PPI treatment increased the microbial abundance of Streptococcaceae (p = 0.004), Leuconostacaceae (p = 0.001), and Pasteurellaceae (p = 0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p = 0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p < 0.05) along with other species present in the multi-strain probiotic. CONCLUSION: Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS. GOV, NUMBER: NCT03327051.

Treatment-refractory ulcerative colitis responsive to indigo naturalis.

BACKGROUND: Indigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model. METHODS: This open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression. RESULTS: Ten of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN. CONCLUSION: IN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation. TRIAL REGISTRATION NUMBER: NCT02442960.

International Survey on Severe Acute Respiratory Syndrome Coronavirus 2 and Acute Pancreatitis Co-occurrence in Children.

OBJECTIVES: It is unknown to what extent coronavirus 2019 (COVID-19) may co-occur with acute pancreatitis (AP) in children and how their clinical course may differ from children with AP alone. METHODS: An online survey was sent to pediatric gastroenterologists to report on COVID-19 and AP cases from December 11, 2020, to February 26, 2021. RESULTS: From 72 respondents (20 countries, 5 continents), 22 cases of positive COVID-19 infection and AP were reported. Patients were predominantly White or Hispanic/Latinx (73%), female (68%), and adolescents (68%). For 86% of patients, this was their first episode of AP. Sixty-eight percent of positive COVID-19 tests were polymerase chain reaction based. There was significant morbidity; 60% required intensive care, 45% had multiorgan involvement, and 24% developed shock. Eleven percent had pancreatic necrosis. Abnormal clotting and systemic inflammatory laboratories were common (31%-92% and 93%, respectively). Median length of symptomatic pancreatitis recovery was 1.8× longer than AP without COVID-19. CONCLUSIONS: Coronavirus 2019 infection and AP co-occur primarily in children without a prior history of pancreatitis. Given the increased need for intensive care, multiorgan involvement, and potentially higher risk for pancreatic necrosis, pediatric providers should have a high level of suspicion for AP in children with COVID-19 infection.