Gut最新文献

In the past 5 years, clinical trials on immune checkpoint inhibitors (ICIs) for the treatment of locally advanced rectal cancer (LARC) have flourished globally, and China has become one of the leading regions in this field. In response to the breakthrough progress and accumulation of evidence from key clinical trials, the Chinese Society of Colorectal Surgery has recognised the need for updated consensus guidance on the development of perioperative and organ-preserving treatment strategies for LARC. This expert consensus guidance provided unified standards for the indications, medication regimens, efficacy evaluations and follow-up of ICIs in this population, with a focus mainly on perioperative management and organ-sparing strategies. The diagnostic part of this consensus guidance is based on the internationally recognised definition of mismatch repair/microsatellite instability detection and emphasises the importance of multidisciplinary teams in treatment decision-making. In terms of treatment, based on the results of key trials that have changed clinical practice in the past 5 years, this expert consensus provides graded recommendations for the duration of preoperative immunotherapy and the necessity of postoperative adjuvant therapy, local resection and organ preservation strategies. Moreover, we refined the management process for the safety of perioperative immunotherapy. This document aims to provide a reference for surgeons; internal medicine, radiation therapy, pathology and imaging physicians; patients and nursing staff involved in the treatment of LARC, as well as health policy makers.

Background: Gut microbiota dysbiosis is linked to autism spectrum disorder (ASD) in children. However, the role of bacterial genomic structural variations (SVs) in ASD remains largely unexplored.

Objective: We aimed to identify bacterial SVs associated with ASD and explore their mechanistic role and clinical application.

Design: We collected faecal metagenomes from 452 children (261 ASD, 191 neurotypical) across an in-house and seven public datasets. Using linear mixed-effects modelling, we identified ASD-associated SVs and compositional shifts and validated candidate SVs in humanised gut microbiome mice.

Results: We identified 100 bacterial SVs significantly associated with ASD (p<0.05). These SVs were enriched in genes involved in critical biological processes, including ion and amino acid metabolism and bacterial growth regulation in ASD. In particular, we found important SVs in Bacteroides uniformis related to thiamine and iron metabolism. Moreover, SVs in Ruminococcus torques were associated with the MazF (endoribonuclease toxin) and MazE (antitoxin) system, a key regulator of pathobiont proliferation. Validation in humanised mouse models confirmed significant correlations between these SV signatures and ASD-like behaviours, such as reduced social interaction and increased repetitive behaviours. Both phylogeographically conserved and regionally restricted SVs showed strong associations with ASD. A diagnostic model combining nine SVs and three bacterial species achieved an area under the receiver operating characteristic curve of 81.1%, outperforming models based solely on variable SVs (79.1%), deletion SVs (75.2%) or bacterial species abundance alone (72.3%).

Conclusion: Our findings suggest the significant role of bacterial genomic SVs in ASD and highlight their potential as diagnostic biomarkers.