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      Clostridium butyricum potentially improves inflammation and immunity through alteration of the microbiota and metabolism of gastric cancer patients after gastrectomy

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          Abstract

          Background

          Gastrectomy is the most effective treatment to improve the clinical survival rate of patients with gastric cancer. However, the pathophysiological changes caused by gastrectomy have seriously affected the postoperative recovery.

          Methods

          In the present trial, Ataining (containing C. butyricum, CGMCC0313.1) was applied in patients after gastrectomy to investigate the effect of C. butyricum on the early postoperative recovery by monitoring the inflammatory immune response with blood indicators, detecting the gut microbiota with high-throughput sequencing, and analyzing the short-chain fatty acids (SCFAs) with targeted metabolomics. This study is registered with the number ChiCTR2000040915.

          Results

          Our outcomes revealed that C. butyricum had significantly reduced the number of Leucocyte ( P < 0.001), the percentage of Neutrophil ( P < 0.001), the expression of IL-1β ( P < 0.01), IL-6 ( P < 0.05), and TNF-α ( P < 0.01), while markedly enhanced the immunity indexes (immunoglobulin and lymphocyte) ( P < 0.05) and nutrition indexes (albumin and total protein) ( P < 0.05). In addition, the use of the C. butyricum greatly enriched the relative abundance of beneficial bacteria Bacteroides, Faecalibacterium and Gemmiger, while the abundance of pathogenic Streptococcus, Desulfovibrio and Actinomyces were markedly decreased at genus level. We also observed significant up-regulation of SCFAs, including acetic acid, propionic acid, butyric acid and isobutyric acid, after C. butyricum administration in patients receiving gastrectomy.

          Conclusion

          Therefore, evidence supported that oral administration of C. butyricum after gastrectomy can reduce early postoperative inflammation, enhance immune ability, restore intestinal microbiota eubiosis, increase intestinal SCFAs, reduce the occurrence of postoperative complications, and ultimately promote the early recovery of the patient.

          Clinical trial registration

          http://www.chictr.org.cn/, identifier (ChiCTR2000040915).

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          Most cited references45

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            UPARSE: highly accurate OTU sequences from microbial amplicon reads.

            Amplified marker-gene sequences can be used to understand microbial community structure, but they suffer from a high level of sequencing and amplification artifacts. The UPARSE pipeline reports operational taxonomic unit (OTU) sequences with ≤1% incorrect bases in artificial microbial community tests, compared with >3% incorrect bases commonly reported by other methods. The improved accuracy results in far fewer OTUs, consistently closer to the expected number of species in a community.
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              Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.

              The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                17 November 2022
                2022
                : 13
                : 1076245
                Affiliations
                [1] 1 Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University , Nanchang, China
                [2] 2 HuanKui Academy, Nanchang University , Nanchang, China
                [3] 3 Queen Mary College, Nanchang University , Nanchang, China
                [4] 4 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University , Nanchang, China
                [5] 5 National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University , Nanchang, China
                Author notes

                Edited by: Zhihong Sun, Inner Mongolia Agricultural University, China

                Reviewed by: Fen Zhang, The Chinese University of Hong Kong, China; Huajun Li, Dalian Medical University, China

                *Correspondence: Xiaorong Deng, dengxr77@ 123456163.com ; Tingtao Chen, chentingtao1984@ 123456163.com

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1076245
                9714544
                36466862
                95343789-3649-46a1-8b94-54c59fc77e8d
                Copyright © 2022 Cao, Zheng, Xu, Jin, Huang, Shi, He, Luo, Liu, Liu, Wei, Deng and Chen

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 October 2022
                : 07 November 2022
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 45, Pages: 14, Words: 6044
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81960103, 82060638
                Funded by: Natural Science Foundation of Jiangxi Province , doi 10.13039/501100004479;
                Award ID: 20202ACBL206010, 20192ACBL20034
                Categories
                Immunology
                Clinical Trial

                Immunology
                gastric cancer,clostridium butyricum,scfas,gut microbiota,gastrectomy
                Immunology
                gastric cancer, clostridium butyricum, scfas, gut microbiota, gastrectomy

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