Association of gut microbiome with COPD in Japanese male residents: the SESSA study

Background: Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods: This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46-76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results: The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and β-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion: Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.journal articl

Gastric Invasive Micropapillary Carcinoma with Intestinal Phenotypes Harboring a TP53 R175H Mutation

We report a case of gastric invasive micropapillary carcinoma (IMPC) in an 86-year-old female patient. She was admitted to our hospital with a chief complaint of bloody emesis. Upper gastrointestinal endoscopy found a gastric adenocarcinoma at the antrum. The biopsy specimens showed moderately differentiated adenocarcinoma with invasive small tumor nests. Distal gastrectomy with systematic lymph node dissection demonstrated that the tumor had IMPC through a pathological examination. Despite the depth of tumor invasion (the submucosa), extensive lymph node metastases were observed. Anti-D2-40 immunostaining revealed numerous infiltrating tumor cell nests in the lymphatic vessels, which could explain subsequent multiple lymph node metastases. The adenocarcinoma showed intestinal phenotypes by several immunohistochemical studies. One of these antibodies (CD10) clearly demonstrated the inverted apical-basal (inside-out) pattern of IMPC, whereas it showed an ordinary pattern in intestinal metaplasia adjacent to the tumor. Furthermore, genetic analysis by direct sequencing revealed a point mutation in the exon 5 of TP53 in the tumor. The mutation presumably harbors a missense mutation from Arg to His at the codon 175 (R175H). R175H has been previously described as a ‘gain-of-function' mutation with a high invasive or metastatic potential in several types of cancers. In summary, this is one of the first reported cases of gastric IMPC with intestinal phenotypes harboring a TP53 R175H mutation in the literature