Kong, Yong

Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance.

Abstract Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with β-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6–71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6–10, and 19–25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children.

Cholangiocarcinoma (CCA) is the second most common malignancy arising in the liver. It carries a poor prognosis, in part because its pathogenesis is not well understood. The type 3 inositol 1,4,5‐trisphosphate receptor (ITPR3) is the principal intracellular calcium ion (Ca2+) release channel in cholangiocytes, and its increased expression has been related to the pathogenesis of malignancies in other types of tissues, so we investigated its role in CCA. ITPR3 expression was increased in both hilar and intrahepatic CCA samples as well as in CCA cell lines. Deletion of ITPR3 from CCA cells impaired proliferation and cell migration. A bioinformatic analysis suggested that overexpression of ITPR3 in CCA would have a mitochondrial phenotype, so this was also examined. ITPR3 normally is concentrated in a subapical region of endoplasmic reticulum (ER) in cholangiocytes, but both immunogold electron microscopy and super‐resolution microscopy showed that ITPR3 in CCA cells was also in regions of ER in close association with mitochondria. Deletion of ITPR3 from these cells impaired mitochondrial Ca2+ signaling and led to cell death. Conclusion: ITPR3 expression in cholangiocytes becomes enhanced in CCA. This contributes to malignant features, including cell proliferation and migration and enhanced mitochondrial Ca2+ signaling.