Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice.

BACKGROUND: Triclosan, an antimicrobial agent in personal care products, could be absorbed into the human body through the digestive tract. This animal experiment aimed to clarify the effects of triclosan exposure on the microbiome and intestinal immune functions in healthy and ulcerative colitis models. METHODS: Balb/c mice were maintained on an AIN-93G diet containing 80ppm triclosan dissolved in polyethylene as vehicle or vehicle alone for 1 week or 4 weeks. In the end, the mice were sacrificed, blood samples and colon tissues were collected for analysis of inflammation, and fecal samples were collected for 16 S rRNA sequencing of gut microbiota. To establish ulcerative colitis mice model, at the beginning of the 4th week, mice maintained on the diet with or without triclosan were treated with 2% Dextran sulfate sodium(DSS) in drinking water for 1 week. Then mice were sacrificed for analysis of colitis and gut microbiota. RESULTS: Triclosan exposure to common mice enhanced the levels of p-NF-κb and Toll-like receptor 4 (TLR4), and decreased the Occludin in the colon. Triclosan exposure to DSS-induced mice increased the level of inflammatory cytokines, reduced the levels of Occludin, and exacerbated the degree of damage to intestinal mucosa and crypt, infiltration of inflammatory cells and atypia of glandular cells. Low-grade intraepithelial neoplasia appeared. Both in common and DSS-induced mice, triclosan exposure changed the diversity and composition of gut microbiota. Fecal samples showed higher enrichment of sulfate-reducing bacteria and Bacteroides, and less butyrate-producing bacteria. CONCLUSION: Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice. And changes in the composition of gut microbiota were characterized by the increase of harmful bacteria, including sulfate-reducing bacteria and Bacteroides, and the reduction of protective probiotics, butyrate-producing bacteria.

Efficacy and safety of different doses of baricitinib for rheumatoid arthritis: A Bayesian network meta-analysis.

BACKGROUND: To evaluate the comparative efficacy and safety of baricitinib with different dosages in patients with rheumatoid arthritis (RA). METHODS: PubMed, Embase, and the Cochrane Library were retrieved by computer to gather randomized controlled trials (RCTs) of baricitinib for RA from their beginning to September 2021. After 2 researchers independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed, and Bayesian network meta-analysis was performed by GeMTC0.14.3 and Stata15.1 software. RESULTS: Ten publications reporting 9 RCTs were included, with 4129 patients randomized to receive 1 of the 7 interventions. Seven interventions were baricitinib 1 mg + conventional disease-modifying antirheumatic drugs (cDMARD), baricitinib 2 mg + cDMARD, baricitinib 4 mg + cDMARD, baricitinib 8 mg + cDMARD, baricitinib 4 mg, placebo + cDMARD, and cDMARD. In the efficacy outcomes at 12 weeks, nearly all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 8 mg combined with cDMARD might have the best curative effect in most outcomes. In the efficacy outcomes at 24 weeks, all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 4 mg monotherapy might have the best curative effect in most outcomes. The intervention with the highest incidence of adverse events (AEs) might be baricitinib 8 mg combined with cDMARD, and the intervention with the highest incidence of infections might be baricitinib 4 mg combined with cDMARD. CONCLUSIONS: Baricitinib 8 mg combined with cDMARDs was suitable for short-term control of RA symptoms, and baricitinib 4 mg was more effective for treating RA over a longer period of time. But attention should be paid for the risk of baricitinib at 4 to 8 mg in clinical application due to the high incidence of AEs and infections.