Antibiotics and probiotics impact gut antimicrobial resistance gene reservoir in COVID-19 patients.

Dysbiosis of gut microbiota is well-described in patients with coronavirus 2019 (COVID-19), but the dynamics of antimicrobial resistance genes (ARGs) reservoir, known as resistome, is less known. Here, we performed longitudinal fecal metagenomic profiling of 142 patients with COVID-19, characterized the dynamics of resistome from diagnosis to 6 months after viral clearance, and reported the impact of antibiotics or probiotics on the ARGs reservoir. Antibiotic-naive patients with COVID-19 showed increased abundance and types, and higher prevalence of ARGs compared with non-COVID-19 controls at baseline. Expansion in resistome was mainly driven by tetracycline, vancomycin, and multidrug-resistant genes and persisted for at least 6 months after clearance of SARS-CoV-2. Patients with expanded resistome exhibited increased prevalence of Klebsiella sp. and post-acute COVID-19 syndrome. Antibiotic treatment resulted in further increased abundance of ARGs whilst oral probiotics (synbiotic formula, SIM01) significantly reduced the ARGs reservoir in the gut microbiota of COVID-19 patients during the acute infection and recovery phase. Collectively, these findings shed new insights on the dynamic of ARGs reservoir in COVID-19 patients and the potential role of microbiota-directed therapies in reducing the burden of accumulated ARGs.

Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events.

OBJECTIVE: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty). DESIGN: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA. RESULTS: We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05). CONCLUSION: Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.

Electroacupuncture plus on-demand gastrocaine for refractory functional dyspepsia: Pragmatic randomized trial.

BACKGROUND AND AIM: Treatment options for functional dyspepsia (FD) refractory to pharmacological treatments are limited but the effectiveness of electroacupuncture (EA) is uncertain. We assessed the effectiveness of EA combined with on-demand gastrocaine. METHODS: We conducted a single-center, assessor-blind, randomized parallel-group 2-arm trial on Helicobacter pylori negative FD patients of the postprandial distress syndrome subtype refractory to proton pump inhibitor, prokinetics, or H2 antagonists. Enrolled participants were block randomized in a 1:1 ratio, with concealed random sequence. The treatment and control groups both received on-demand gastrocaine for 12 weeks, but only those in treatment group were offered 20 sessions of EA over 10 weeks. The primary endpoint was the between-group difference in proportion of patients achieving adequate relief of symptoms at week 12. RESULTS: Of 132 participants randomly assigned to EA plus on-demand gastrocaine (n = 66) or on-demand gastrocaine alone (n = 66), 125 (94.7%) completed all follow-up at 12 weeks. The EA group had a compliance rate 97.7%. They had a significantly higher likelihood in achieving adequate symptom relief at 12 weeks, with a clinically relevant number needed to treat (NNT) value of 2.36 (95% CI: 1.74, 3.64). Among secondary outcomes, statistically and clinically significant improvements were observed among global symptom (NNT = 3.85 [95% CI: 2.63, 7.69]); postprandial fullness and early satiation (NNT = 5.00 [95% CI: 2.86, 25.00]); as well as epigastric pain, epigastric burning, and postprandial nausea (NNT = 4.17 [95% CI: 2.56, 11.11]). Adverse events were minimal and nonsignificant. CONCLUSION: For refractory FD, EA provides significant, clinically relevant symptom relief when added to on-demand gastrocaine (ChiCTR-IPC-15007109).

Effectiveness of reminder strategies on cancer screening adherence: a randomised controlled trial.

BACKGROUND: Few randomised controlled trials (RCTs) have evaluated the different recalling approaches for enhancing adherence to faecal immunochemical test (FIT)-based screening. AIM: The authors evaluated the effectiveness of two telecommunication strategies on improving adherence to yearly FIT screening. DESIGN AND SETTING: A randomised, parallel group trial was performed in a primary care screening practice. METHOD: The authors recruited 629 asymptomatic individuals aged 40-70 years with a negative FIT in 2015 to a population-based screening programme. On participation, they were invited to repeat their second round of FIT in 2016, 12 months after the first test. Each participant was randomly assigned to either interactive telephone reminder (n = 207), short message service reminder (SMS, n = 212), or control, where no additional interventions were delivered after the findings of their first FIT was communicated to the participants (n = 210). Reminders in the intervention groups were delivered 1 month before subjects' expected return. Additional telephone reminders were delivered 2 months after the expected return date to all subjects who defaulted specimen return. The outcomes included rates of FIT collection and specimen return up to 6 months after their expected return. RESULTS: At 6 months, the cumulative FIT collection rate was 95.1%, 90.4%, and 86.5%, respectively, for the telephone, SMS, and control groups (P = 0.010). The corresponding specimen return rate was 94.1%, 90.0%, and 86.0% (P = 0.022). When compared with the control, only subjects in the telephone group were significantly more likely to collect FIT tubes (adjusted odds ratio [AOR] 3.18, 95% confidence interval [CI] = 1.50 to 6.75, P = 0.003) and return completed specimens (AOR = 2.73, 95% CI = 1.35 to 5.53, P = 0.005). CONCLUSION: Interactive telephone reminders are effective at securing previously screened subjects to repeat screening 1 year after a negative finding.